Complete mitochondrial genome of Taharana fasciana (Insecta, Hemiptera: Cicadellidae) and comparison with other Cicadellidae insects.

PubMed

Wang, Jiajia; Li, Hu; Dai, Renhuai

2017-12-01

Here, we describe the first complete mitochondrial genome (mitogenome) sequence of the leafhopper Taharana fasciana (Coelidiinae). The mitogenome sequence contains 15,161 bp with an A + T content of 77.9%. It includes 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and one non-coding (A + T-rich) region; in addition, a repeat region is also present (GenBank accession no. KY886913). These genes/regions are in the same order as in the inferred insect ancestral mitogenome. All protein-coding genes have ATN as the start codon, and TAA or single T as the stop codons, except the gene ND3, which ends with TAG. Furthermore, we predicted the secondary structures of the rRNAs in T. fasciana. Six domains (domain III is absent in arthropods) and 41 helices were predicted for 16S rRNA, and 12S rRNA comprised three structural domains and 24 helices. Phylogenetic tree analysis confirmed that T. fasciana and other members of the Cicadellidae are clustered into a clade, and it identified the relationships among the subfamilies Deltocephalinae, Coelidiinae, Idiocerinae, Cicadellinae, and Typhlocybinae.

A xylose-stimulated xylanase-xylose binding protein chimera created by random nonhomologous recombination.

PubMed

Ribeiro, Lucas Ferreira; Tullman, Jennifer; Nicholes, Nathan; Silva, Sérgio Ruschi Bergamachi; Vieira, Davi Serradella; Ostermeier, Marc; Ward, Richard John

2016-01-01

Saccharification of lignocellulosic material by xylanases and other glycoside hydrolases is generally conducted at high concentrations of the final reaction products, which frequently inhibit the enzymes used in the saccharification process. Using a random nonhomologous recombination strategy, we have fused the GH11 xylanase from Bacillus subtilis (XynA) with the xylose binding protein from Escherichia coli (XBP) to produce an enzyme that is allosterically stimulated by xylose. The pT7T3GFP_XBP plasmid containing the XBP coding sequence was randomly linearized with DNase I, and ligated with the XynA coding sequence to create a random XynA-XBP insertion library, which was used to transform E. coli strain JW3538-1 lacking the XBP gene. Screening for active XBP was based on the expression of GFP from the pT7T3GFP_XBP plasmid under the control of a xylose inducible promoter. In the presence of xylose, cells harboring a functional XBP domain in the fusion protein (XBP+) showed increased GFP fluorescence and were selected using FACS. The XBP+ cells were further screened for xylanase activity by halo formation around xylanase producing colonies (XynA+) on LB-agar-xylan media after staining with Congo red. The xylanase activity ratio with xylose/without xylose in supernatants from the XBP+/XynA+ clones was measured against remazol brilliant blue xylan. A clone showing an activity ratio higher than 1.3 was selected where the XynA was inserted after the asparagine 271 in the XBP, and this chimera was denominated as XynA-XBP271. The XynA-XBP271 was more stable than XynA at 55 °C, and in the presence of xylose the catalytic efficiency was ~3-fold greater than the parental xylanase. Molecular dynamics simulations predicted the formation of an extended protein-protein interface with coupled movements between the XynA and XBP domains. In the XynA-XBP271 with xylose bound to the XBP domain, the mobility of a β-loop in the XynA domain results in an increased access to the active site, and may explain the observed allosteric activation. The approach presented here provides an important advance for the engineering enzymes that are stimulated by the final product.

An Analysis of Coherent Digital Receivers in the Presence of Colored Noise Interference.

DTIC Science & Technology

1985-06-01

115 6.4 Pe for Det-erministic Jamnmers, JSR = 0.01, E0.3---------------------------------------------116 6.5 Pe for Deterministic Jamnmers, JSR = 0.1...k k where h p(t) and hhi(t) are the particular and homogeneous solutions, respectively, to a differential equation derived from the Fredholm I...yields 2 2D(s2)c (s) = N(s ) (3.4)c Multiplication by s corresponds to differentiation with respect to t in the time domain. So, Eq. (3.4) becomes D(p 2)K

A cross-sectional study of chiropractic students' research readiness using the Academic Self-Concept Analysis Scale.

PubMed

Whillier, Stephney; Au, Kent; Feng, Louie; Su, Helen

2017-10-01

The shift toward evidence-based health care has reoriented tertiary clinical education in a way that necessitates and incorporates research. This study assesses the inclination and suitability of chiropractic students for research over a 5-year educational program. Research attributes of chiropractic students were assessed in this cross-sectional study using a validated and modified academic self-concept analysis scale. Students in first and final year were assessed in 4 domains: creativity, motivation, self-regulation, and general intellectual ability. Univariable differences were assessed using Welch 2-sample t tests, and multivariable analysis was carried out with multiple linear regression models. The response rate was 71% (n = 165). First- and fifth-year students scored highly on all 4 domains (80% to 96%). Compared to first-year students, fifth-year students rated themselves significantly lower in 3 of the domains: general intellectual abilities (t[126] = -2.01; p = 0.047), motivation (t[115] = -4.82; p < 0.001), and creativity (t[136] = -3.00; p = 0.003). Research suitability is high in chiropractic students. Both cohorts scored high in all domains despite the disparity between first and fifth years. First-year students outperformed fifth-year students in 3 domains, indicating a potential decline in the inclination to do research over time. However, unaccounted factors, such as the Dunning-Kruger effect, life changes, and "burnout," may have contributed to these differences. Future studies should include questions about stress, fatigue, clinical orientation, and educational environment to inform the interpretation of findings.

Experimental identification of closely spaced modes using NExT-ERA

NASA Astrophysics Data System (ADS)

Hosseini Kordkheili, S. A.; Momeni Massouleh, S. H.; Hajirezayi, S.; Bahai, H.

2018-01-01

This article presents a study on the capability of the time domain OMA method, NExT-ERA, to identify closely spaced structural dynamic modes. A survey in the literature reveals that few experimental studies have been conducted on the effectiveness of the NExT-ERA methodology in case of closely spaced modes specifically. In this paper we present the formulation for NExT-ERA. This formulation is then implemented in an algorithm and a code, developed in house to identify the modal parameters of different systems using their generated time history data. Some numerical models are firstly investigated to validate the code. Two different case studies involving a plate with closely spaced modes and a pulley ring with greater extent of closeness in repeated modes are presented. Both structures are excited by random impulses under the laboratory condition. The resulting time response acceleration data are then used as input in the developed code to extract modal parameters of the structures. The accuracy of the results is checked against those obtained from experimental tests.

Health-related quality of life following radical prostatectomy: long-term outcomes.

PubMed

Matthew, Andrew G; Alibhai, Shabbir M H; Davidson, Tal; Currie, Kristen L; Jiang, Haiyan; Krahn, Murray; Fleshner, Neil E; Kalnin, Robin; Louis, Alyssa S; Davison, B Joyce; Trachtenberg, John

2014-10-01

To identify the health-related quality of life (HRQoL) domains that radical prostatectomy (RP) impacts most negatively and to define the recovery of these domains over 30 months of observation. A total of 1,200 RP patients completed the Patient-Oriented Prostate Utility Scale-Psychometric (PORPUS-P; range 0-100, higher is better), a prostate cancer-specific HRQoL measure, prior to RP and at 0-3 (T1), 3-9 (T2), 9-18 (T3) and 18-30 (T4) months post-RP. HRQoL changes were examined using paired t tests and a mixed-effect growth curve model. Multivariable analyses were performed to investigate demographic and treatment factors predicting the change in HRQoL. Mean baseline PORPUS-P score, 83.1, fell to 66.5 (p < 0.001) at T1. Over time HRQoL improved but did not return to baseline (T4 mean 76.4, p < 0.001). Domain analysis revealed that sexual function (p < 0.001), sexual drive (p < 0.001), energy (p = 0.001) and bladder control (p < 0.001) failed to return to baseline at T4. Sexual function demonstrated the greatest impairment overall. The multivariable model revealed Black men experienced greater losses in global HRQoL compared with White men (coefficient -2.77, 95% CI -5.00 to -0.54, p = 0.015). High baseline HRQoL, pro-erectile aid use and bilateral nerve-sparing were significantly associated with smaller reductions in HRQoL post-RP. Overall HRQoL, sexual drive, sexual function, energy and bladder control do not return to preoperative levels within 30 months post-RP. Black patients experience the greatest reductions in HRQoL. HRQoL losses may be ameliorated by use of pro-erectile aids. These findings help to identify at-risk patient populations and inform survivorship programs.

Structural Phylogenomics Retrodicts the Origin of the Genetic Code and Uncovers the Evolutionary Impact of Protein Flexibility

PubMed Central

Caetano-Anollés, Gustavo; Wang, Minglei; Caetano-Anollés, Derek

2013-01-01

The genetic code shapes the genetic repository. Its origin has puzzled molecular scientists for over half a century and remains a long-standing mystery. Here we show that the origin of the genetic code is tightly coupled to the history of aminoacyl-tRNA synthetase enzymes and their interactions with tRNA. A timeline of evolutionary appearance of protein domain families derived from a structural census in hundreds of genomes reveals the early emergence of the ‘operational’ RNA code and the late implementation of the standard genetic code. The emergence of codon specificities and amino acid charging involved tight coevolution of aminoacyl-tRNA synthetases and tRNA structures as well as episodes of structural recruitment. Remarkably, amino acid and dipeptide compositions of single-domain proteins appearing before the standard code suggest archaic synthetases with structures homologous to catalytic domains of tyrosyl-tRNA and seryl-tRNA synthetases were capable of peptide bond formation and aminoacylation. Results reveal that genetics arose through coevolutionary interactions between polypeptides and nucleic acid cofactors as an exacting mechanism that favored flexibility and folding of the emergent proteins. These enhancements of phenotypic robustness were likely internalized into the emerging genetic system with the early rise of modern protein structure. PMID:23991065

Three-dimensional time domain model of lightning including corona effects

NASA Technical Reports Server (NTRS)

Podgorski, Andrew S.

1991-01-01

A new 3-D lightning model that incorporates the effect of corona is described for the first time. The new model is based on a Thin Wire Time Domain Lightning (TWTDL) Code developed previously. The TWTDL Code was verified during the 1985 and 1986 lightning seasons by the measurements conducted at the 553 m CN Tower in Toronto, Ontario. The inclusion of corona in the TWTDL code allowed study of the corona effects on the lightning current parameters and the associated electric field parameters.

A cross-sectional study of chiropractic students' research readiness using the Academic Self-Concept Analysis Scale

PubMed Central

Whillier, Stephney; Au, Kent; Feng, Louie; Su, Helen

2017-01-01

Objective: The shift toward evidence-based health care has reoriented tertiary clinical education in a way that necessitates and incorporates research. This study assesses the inclination and suitability of chiropractic students for research over a 5-year educational program. Methods: Research attributes of chiropractic students were assessed in this cross-sectional study using a validated and modified academic self-concept analysis scale. Students in first and final year were assessed in 4 domains: creativity, motivation, self-regulation, and general intellectual ability. Univariable differences were assessed using Welch 2-sample t tests, and multivariable analysis was carried out with multiple linear regression models. Results: The response rate was 71% (n = 165). First- and fifth-year students scored highly on all 4 domains (80% to 96%). Compared to first-year students, fifth-year students rated themselves significantly lower in 3 of the domains: general intellectual abilities (t[126] = −2.01; p = 0.047), motivation (t[115] = −4.82; p < 0.001), and creativity (t[136] = −3.00; p = 0.003). Conclusion: Research suitability is high in chiropractic students. Both cohorts scored high in all domains despite the disparity between first and fifth years. First-year students outperformed fifth-year students in 3 domains, indicating a potential decline in the inclination to do research over time. However, unaccounted factors, such as the Dunning-Kruger effect, life changes, and “burnout,” may have contributed to these differences. Future studies should include questions about stress, fatigue, clinical orientation, and educational environment to inform the interpretation of findings. PMID:28768108

Expression of the leukemia-associated CBF{beta}/SMMHC chimeric gene causes transformation of 3T3 cells

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

Hajra, A.; Liu, P.; Collins, E.S.

1994-09-01

A pericentric inversion of chromosome 16 (inv(16)(p13;q22)) is consistently seen in acute myeloid leukemia of the M4Eo subtype. This inversion fuses almost the entire coding region of the gene encoding of the {beta} subunit of the heterodimeric transcription factor CBF/PEBP2 to the region of the MYH11 gene encoding the rod domain for the smooth muscle myosin heavy chain (SMMHC). To investigate the biological properties of the CBF{beta}/SMMHC fusion protein, we have generated 3T3 cell lines that stably express the CBF{beta}/SMMHC chimeric cDNA or the normal, nonchimeric CBF{beta} and SMMHC cDNAs. 3T3 cells expressing CBF{beta}/SMMHC acquire a transformed phenotype, as indicatedmore » by altered cell morphology, formation of foci, and growth in soft agar. Cells constitutively overexpressing the normal CBF{beta} cDNA or the rod region of SMMHC remain nontransformed. Western blot analysis using antibodies to CBF{beta} and the SMMHC rod demonstrates that stably transfected cells express the appropriate chimeric or normal protein. Electrophoretic mobility shift assays reveal that cells transformed by the chimeric cDNA do not have a CBF-DNA complex of the expected mobility, but instead contain a large complex with CBF DNA-binding activity that fails to migrate out of the gel wells. In order to define the regions of CBF{beta}/SMMHC necessary for 3T3 transformation, we have stably transfected cells with mutant CBF{beta}/SMMHC cDNAs containing various deletions of the coding region. Analysis of these cell lines indicates that the transformation property of CBF{beta}/SMMHC requires regions of CBF{beta} known to be necessary for association with the DNA-binding CBF{alpha} subunit, and also requires an intact SMMHC carboxyl terminus, which is necessary for formation of the coiled coil domain of the myosin rod.« less

Improvement of Mishchenko's T-matrix code for absorbing particles.

PubMed

Moroz, Alexander

2005-06-10

The use of Gaussian elimination with backsubstitution for matrix inversion in scattering theories is discussed. Within the framework of the T-matrix method (the state-of-the-art code by Mishchenko is freely available at http://www.giss.nasa.gov/-crmim), it is shown that the domain of applicability of Mishchenko's FORTRAN 77 (F77) code can be substantially expanded in the direction of strongly absorbing particles where the current code fails to converge. Such an extension is especially important if the code is to be used in nanoplasmonic or nanophotonic applications involving metallic particles. At the same time, convergence can also be achieved for large nonabsorbing particles, in which case the non-Numerical Algorithms Group option of Mishchenko's code diverges. Computer F77 implementation of Mishchenko's code supplemented with Gaussian elimination with backsubstitution is freely available at http://www.wave-scattering.com.

tRNA acceptor stem and anticodon bases form independent codes related to protein folding

PubMed Central

Carter, Charles W.; Wolfenden, Richard

2015-01-01

Aminoacyl-tRNA synthetases recognize tRNA anticodon and 3′ acceptor stem bases. Synthetase Urzymes acylate cognate tRNAs even without anticodon-binding domains, in keeping with the possibility that acceptor stem recognition preceded anticodon recognition. Representing tRNA identity elements with two bits per base, we show that the anticodon encodes the hydrophobicity of each amino acid side-chain as represented by its water-to-cyclohexane distribution coefficient, and this relationship holds true over the entire temperature range of liquid water. The acceptor stem codes preferentially for the surface area or size of each side-chain, as represented by its vapor-to-cyclohexane distribution coefficient. These orthogonal experimental properties are both necessary to account satisfactorily for the exposed surface area of amino acids in folded proteins. Moreover, the acceptor stem codes correctly for β-branched and carboxylic acid side-chains, whereas the anticodon codes for a wider range of such properties, but not for size or β-branching. These and other results suggest that genetic coding of 3D protein structures evolved in distinct stages, based initially on the size of the amino acid and later on its compatibility with globular folding in water. PMID:26034281

Objective Measurement of Arterial Flow Before and After Transcatheter Arterial Chemoembolization: A Feasibility Study Using Quantitative Color-Coding Analysis.

PubMed

Lin, Yi-Yang; Lee, Rheun-Chuan; Tseng, Hsiuo-Shan; Liu, Chien-An; Guo, Wan-Yuo; Chang, Cheng-Yen

2015-12-01

To quantitatively measure the hemodynamic change of hepatic artery before and after transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) by quantitative color-coding analysis (QCA). This prospective study registered 64 consecutive HCC patients who underwent segmental or subsegmental TACE with epirubicin and lipiodol at level 2 or 3 of the subjective angiographic chemoembolization endpoint. QCA was used to determine the maximal density time (T(max)) of selected intravascular region of interest (ROI). Relative T(max) (rT(max)) was defined as the T(max) at the selected ROI minus the time of contrast medium spurting from the catheter tip. The rT(max) of hepatic arteries was analyzed before and after embolization. The pre- and post-treatment rT(max) of the landmarks at the treated segmental artery were 1.96 ± 0.48 and 3.14 ± 1.77 s, p < 0.001. According to the treated lobe, 30 patients were treated for the right lobe alone, and 8 patients were treated for the left lobe alone. The pre- and post-rT(max) of treated segmental artery were 2.06 ± 0.54, 3.34 ± 1.63 s, p < 0.001 and 1.89 ± 0.45, 2.68 ± 1.46 s, p = 0.12, respectively. The rT(max) of the proximal lobar hepatic arteries or proper hepatic artery had no significant change before and after TACE. The QCA is feasible to quantify embolization endpoints by comparing the rT(max) in selected hepatic arteries before and after TACE. The rT(max) of treated segmental artery was significant prolonged after optimized procedures.

Collaborative Research: Simulation of Beam-Electron Cloud Interactions in Circular Accelerators Using Plasma Models

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

Katsouleas, Thomas; Decyk, Viktor

Final Report for grant DE-FG02-06ER54888, "Simulation of Beam-Electron Cloud Interactions in Circular Accelerators Using Plasma Models" Viktor K. Decyk, University of California, Los Angeles Los Angeles, CA 90095-1547 The primary goal of this collaborative proposal was to modify the code QuickPIC and apply it to study the long-time stability of beam propagation in low density electron clouds present in circular accelerators. The UCLA contribution to this collaborative proposal was in supporting the development of the pipelining scheme for the QuickPIC code, which extended the parallel scaling of this code by two orders of magnitude. The USC work was as describedmore » here the PhD research for Ms. Bing Feng, lead author in reference 2 below, who performed the research at USC under the guidance of the PI Tom Katsouleas and the collaboration of Dr. Decyk The QuickPIC code [1] is a multi-scale Particle-in-Cell (PIC) code. The outer 3D code contains a beam which propagates through a long region of plasma and evolves slowly. The plasma response to this beam is modeled by slices of a 2D plasma code. This plasma response then is fed back to the beam code, and the process repeats. The pipelining is based on the observation that once the beam has passed a 2D slice, its response can be fed back to the beam immediately without waiting for the beam to pass all the other slices. Thus independent blocks of 2D slices from different time steps can be running simultaneously. The major difficulty was when particles at the edges needed to communicate with other blocks. Two versions of the pipelining scheme were developed, for the the full quasi-static code and the other for the basic quasi-static code used by this e-cloud proposal. Details of the pipelining scheme were published in [2]. The new version of QuickPIC was able to run with more than 1,000 processors, and was successfully applied in modeling e-clouds by our collaborators in this proposal [3-8]. Jean-Luc Vay at Lawrence Berkeley National Lab later implemented a similar basic quasistatic scheme including pipelining in the code WARP [9] and found good to very good quantitative agreement between the two codes in modeling e-clouds. References [1] C. Huang, V. K. Decyk, C. Ren, M. Zhou, W. Lu, W. B. Mori, J. H. Cooley, T. M. Antonsen, Jr., and T. Katsouleas, "QUICKPIC: A highly efficient particle-in-cell code for modeling wakefield acceleration in plasmas," J. Computational Phys. 217, 658 (2006). [2] B. Feng, C. Huang, V. K. Decyk, W. B. Mori, P. Muggli, and T. Katsouleas, "Enhancing parallel quasi-static particle-in-cell simulations with a pipelining algorithm," J. Computational Phys, 228, 5430 (2009). [3] C. Huang, V. K. Decyk, M. Zhou, W. Lu, W. B. Mori, J. H. Cooley, T. M. Antonsen, Jr., and B. Feng, T. Katsouleas, J. Vieira, and L. O. Silva, "QUICKPIC: A highly efficient fully parallelized PIC code for plasma-based acceleration," Proc. of the SciDAC 2006 Conf., Denver, Colorado, June, 2006 [Journal of Physics: Conference Series, W. M. Tang, Editor, vol. 46, Institute of Physics, Bristol and Philadelphia, 2006], p. 190. [4] B. Feng, C. Huang, V. Decyk, W. B. Mori, T. Katsouleas, P. Muggli, "Enhancing Plasma Wakefield and E-cloud Simulation Performance Using a Pipelining Algorithm," Proc. 12th Workshop on Advanced Accelerator Concepts, Lake Geneva, WI, July, 2006, p. 201 [AIP Conf. Proceedings, vol. 877, Melville, NY, 2006]. [5] B. Feng, P. Muggli, T. Katsouleas, V. Decyk, C. Huang, and W. Mori, "Long Time Electron Cloud Instability Simulation Using QuickPIC with Pipelining Algorithm," Proc. of the 2007 Particle Accelerator Conference, Albuquerque, NM, June, 2007, p. 3615. [6] B. Feng, C. Huang, V. Decyk, W. B. Mori, G. H. Hoffstaetter, P. Muggli, T. Katsouleas, "Simulation of Electron Cloud Effects on Electron Beam at ERL with Pipelined QuickPIC," Proc. 13th Workshop on Advanced Accelerator Concepts, Santa Cruz, CA, July-August, 2008, p. 340 [AIP Conf. Proceedings, vol. 1086, Melville, NY, 2008]. [7] B. Feng, C. Huang, V. K. Decyk, W. B. Mori, P. Muggli, and T. Katsouleas, "Enhancing parallel quasi-static particle-in-cell simulations with a pipelining algorithm," J. Computational Phys, 228, 5430 (2009). [8] C. Huang, W. An, V. K. Decyk, W. Lu, W. B. Mori, F. S. Tsung, M. Tzoufras, S. Morshed, T. Antonsen, B. Feng, T. Katsouleas, R., A. Fonseca, S. F. Martins, J. Vieira, L. O. Silva, E. Esarey, C. G. R. Geddes, W. P. Leemans, E. Cormier-Michel, J.-L. Vay, D. L. Bruhwiler, B. Cowan, J. R. Cary, and K. Paul, "Recent results and future challenges for large scale particleion- cell simulations of plasma-based accelerator concepts," Proc. of the SciDAC 2009 Conf., San Diego, CA, June, 2009 [Journal of Physics: Conference Series, vol. 180, Institute of Physics, Bristol and Philadelphia, 2009], p. 012005. [9] J.-L. Vay, C. M. Celata, M. A. Furman, G. Penn, M. Venturini, D. P. Grote, and K. G. Sonnad, ?Update on Electron-Cloud Simulations Using the Package WARP-POSINST.? Proc. of the 2009 Particle Accelerator Conference PAC09, Vancouver, Canada, June, 2009, paper FR5RFP078.« less

Performance of an Optimized Eta Model Code on the Cray T3E and a Network of PCs

NASA Technical Reports Server (NTRS)

Kouatchou, Jules; Rancic, Miodrag; Geiger, Jim

2000-01-01

In the year 2001, NASA will launch the satellite TRIANA that will be the first Earth observing mission to provide a continuous, full disk view of the sunlit Earth. As a part of the HPCC Program at NASA GSFC, we have started a project whose objectives are to develop and implement a 3D cloud data assimilation system, by combining TRIANA measurements with model simulation, and to produce accurate statistics of global cloud coverage as an important element of the Earth's climate. For simulation of the atmosphere within this project we are using the NCEP/NOAA operational Eta model. In order to compare TRIANA and the Eta model data on approximately the same grid without significant downscaling, the Eta model will be integrated at a resolution of about 15 km. The integration domain (from -70 to +70 deg in latitude and 150 deg in longitude) will cover most of the sunlit Earth disc and will continuously rotate around the globe following TRIANA. The cloud data assimilation is supposed to run and produce 3D clouds on a near real-time basis. Such a numerical setup and integration design is very ambitious and computationally demanding. Thus, though the Eta model code has been very carefully developed and its computational efficiency has been systematically polished during the years of operational implementation at NCEP, the current MPI version may still have problems with memory and efficiency for the TRIANA simulations. Within this work, we optimize a parallel version of the Eta model code on a Cray T3E and a network of PCs (theHIVE) in order to improve its overall efficiency. Our optimization procedure consists of introducing dynamically allocated arrays to reduce the size of static memory, and optimizing on a single processor by splitting loops to limit the number of streams. All the presented results are derived using an integration domain centered at the equator, with a size of 60 x 60 deg, and with horizontal resolutions of 1/2 and 1/3 deg, respectively. In accompanying charts we report the elapsed time, the speedup and the Mflops as a function of the number of processors for the non-optimized version of the code on the T3E and theHIVE. The large amount of communication required for model integration explains its poor performance on theHIVE. Our initial implementation of the dynamic memory allocation has contributed to about 12% reduction of memory but has introduced a 3% overhead in computing time. This overhead was removed by performing loop splitting in some of the high demanding subroutines. When the Eta code is fully optimized in order to meet the memory requirement for TRIANA simulations, a non-negligeable overhead may appear that may seriously affect the efficiency of the code. To alleviate this problem, we are considering implementation of a new algorithm for the horizontal advection that is computationally less expensive, and also a new approach for marching in time.

Mechanistic insights into phosphoprotein-binding FHA domains.

PubMed

Liang, Xiangyang; Van Doren, Steven R

2008-08-01

[Structure: see text]. FHA domains are protein modules that switch signals in diverse biological pathways by monitoring the phosphorylation of threonine residues of target proteins. As part of the effort to gain insight into cellular avoidance of cancer, FHA domains involved in the cellular response to DNA damage have been especially well-characterized. The complete protein where the FHA domain resides and the interaction partners determine the nature of the signaling. Thus, a key biochemical question is how do FHA domains pick out their partners from among thousands of alternatives in the cell? This Account discusses the structure, affinity, and specificity of FHA domains and the formation of their functional structure. Although FHA domains share sequence identity at only five loop residues, they all fold into a beta-sandwich of two beta-sheets. The conserved arginine and serine of the recognition loops recognize the phosphorylation of the threonine targeted. Side chains emanating from loops that join beta-strand 4 with 5, 6 with 7, or 10 with 11 make specific contacts with amino acids of the ligand that tailor sequence preferences. Many FHA domains choose a partner in extended conformation, somewhat according to the residue three after the phosphothreonine in sequence (pT + 3 position). One group of FHA domains chooses a short carboxylate-containing side chain at pT + 3. Another group chooses a long, branched aliphatic side chain. A third group prefers other hydrophobic or uncharged polar side chains at pT + 3. However, another FHA domain instead chooses on the basis of pT - 2, pT - 3, and pT + 1 positions. An FHA domain from a marker of human cancer instead chooses a much longer protein fragment that adds a beta-strand to its beta-sheet and that presents hydrophobic residues from a novel helix to the usual recognition surface. This novel recognition site and more remote sites for the binding of other types of protein partners were predicted for the entire family of FHA domains by a bioinformatics approach. The phosphopeptide-dependent dynamics of an FHA domain, SH2 domain, and PTB domain suggest a common theme: rigid, preformed binding surfaces support van der Waals contacts that provide favorable binding enthalpy. Despite the lack of pronounced conformational changes in FHA domains linked to binding events, more subtle adjustments may be possible. In the one FHA domain tested, phosphothreonine peptide binding is accompanied by increased flexibility just outside the binding site and increased rigidity across the beta-sandwich. The folding of the same FHA domain progresses through near-native intermediates that stabilize the recognition loops in the center of the phosphoprotein-binding surface; this may promote rigidity in the interface and affinity for targets phosphorylated on threonine.

WEC3: Wave Energy Converter Code Comparison Project: Preprint

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

Combourieu, Adrien; Lawson, Michael; Babarit, Aurelien

This paper describes the recently launched Wave Energy Converter Code Comparison (WEC3) project and present preliminary results from this effort. The objectives of WEC3 are to verify and validate numerical modelling tools that have been developed specifically to simulate wave energy conversion devices and to inform the upcoming IEA OES Annex VI Ocean Energy Modelling Verification and Validation project. WEC3 is divided into two phases. Phase 1 consists of a code-to-code verification and Phase II entails code-to-experiment validation. WEC3 focuses on mid-fidelity codes that simulate WECs using time-domain multibody dynamics methods to model device motions and hydrodynamic coefficients to modelmore » hydrodynamic forces. Consequently, high-fidelity numerical modelling tools, such as Navier-Stokes computational fluid dynamics simulation, and simple frequency domain modelling tools were not included in the WEC3 project.« less

Time domain simulation of nonlinear acoustic beams generated by rectangular pistons with application to harmonic imaging

NASA Astrophysics Data System (ADS)

Yang, Xinmai; Cleveland, Robin O.

2005-01-01

A time-domain numerical code (the so-called Texas code) that solves the Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation has been extended from an axis-symmetric coordinate system to a three-dimensional (3D) Cartesian coordinate system. The code accounts for diffraction (in the parabolic approximation), nonlinearity and absorption and dispersion associated with thermoviscous and relaxation processes. The 3D time domain code was shown to be in agreement with benchmark solutions for circular and rectangular sources, focused and unfocused beams, and linear and nonlinear propagation. The 3D code was used to model the nonlinear propagation of diagnostic ultrasound pulses through tissue. The prediction of the second-harmonic field was sensitive to the choice of frequency-dependent absorption: a frequency squared f2 dependence produced a second-harmonic field which peaked closer to the transducer and had a lower amplitude than that computed for an f1.1 dependence. In comparing spatial maps of the harmonics we found that the second harmonic had dramatically reduced amplitude in the near field and also lower amplitude side lobes in the focal region than the fundamental. These findings were consistent for both uniform and apodized sources and could be contributing factors in the improved imaging reported with clinical scanners using tissue harmonic imaging. .

Time domain simulation of nonlinear acoustic beams generated by rectangular pistons with application to harmonic imaging.

PubMed

Yang, Xinmai; Cleveland, Robin O

2005-01-01

A time-domain numerical code (the so-called Texas code) that solves the Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation has been extended from an axis-symmetric coordinate system to a three-dimensional (3D) Cartesian coordinate system. The code accounts for diffraction (in the parabolic approximation), nonlinearity and absorption and dispersion associated with thermoviscous and relaxation processes. The 3D time domain code was shown to be in agreement with benchmark solutions for circular and rectangular sources, focused and unfocused beams, and linear and nonlinear propagation. The 3D code was used to model the nonlinear propagation of diagnostic ultrasound pulses through tissue. The prediction of the second-harmonic field was sensitive to the choice of frequency-dependent absorption: a frequency squared f2 dependence produced a second-harmonic field which peaked closer to the transducer and had a lower amplitude than that computed for an f1.1 dependence. In comparing spatial maps of the harmonics we found that the second harmonic had dramatically reduced amplitude in the near field and also lower amplitude side lobes in the focal region than the fundamental. These findings were consistent for both uniform and apodized sources and could be contributing factors in the improved imaging reported with clinical scanners using tissue harmonic imaging.

Evolution of the CD4 family: teleost fish possess two divergent forms of CD4 in addition to lymphocyte activation gene-3

USGS Publications Warehouse

Laing, K.J.; Zou, J.J.; Purcell, M.K.; Phillips, R.; Secombes, C.J.; Hansen, J.D.

2006-01-01

The T cell coreceptor CD4 is a transmembrane glycoprotein belonging to the Ig superfamily and is essential for cell-mediated immunity. Two different genes were identified in rainbow trout that resemble mammalian CD4. One (trout CD4) encodes four extracellular Ig domains reminiscent off mammalian CD4, whereas the other (CD4REL) codes for two Ig domains. Structural motifs within the amino acid sequences suggest that the two Ig domains of CD4REL duplicated to generate the four-domain molecule of CD4 and the related gene, lymphocyte activation gene-3. Here we present evidence that both of these molecules in trout are homologous to mammalian CD4 and that teleosts encode an additional CD4 family member, lymphocyte activation gene-3, which is a marker for activated T cells. The syntenic relationships of similar genes in other teleost and non-fish genomes provide evidence for the likely evolution of CD4-related molecules in vertebrates, with CD4REL likely representing the primordial form in fish. Expression of both CD4 genes is highest in the thymus and spleen, and mRNA expression of these genes is limited to surface IgM- lymphocytes, consistent with a role for T cell functionality. Finally, the intracellular regions of both CD4 and CD4REL possess the canonical CXC motif involved in the interaction off CD4 with p56LCK, implying that similar mechanisms for CD4 + T cell activation are present in all vertebrates. Our results therefore raise new questions about T cell development and functionality in lower vertebrates that cannot be answered by current mammalian models and, thus, is of fundamental importance for understanding the evolution of cell-mediated immunity in gnathosomes. Copyright ?? 2006 by The American Association of Immunologists, Inc.

Ultra-short heart rate variability recording reliability: The effect of controlled paced breathing.

PubMed

Melo, Hiago M; Martins, Thiago C; Nascimento, Lucas M; Hoeller, Alexandre A; Walz, Roger; Takase, Emílio

2018-06-04

Recent studies have reported that Heart Rate Variability (HRV) indices remain reliable even during recordings shorter than 5 min, suggesting the ultra-short recording method as a valuable tool for autonomic assessment. However, the minimum time-epoch to obtain a reliable record for all HRV domains (time, frequency, and Poincare geometric measures), as well as the effect of respiratory rate on the reliability of these indices remains unknown. Twenty volunteers had their HRV recorded in a seated position during spontaneous and controlled respiratory rhythms. HRV intervals with 1, 2, and 3 min were correlated with the gold standard period (6-min duration) and the mean values of all indices were compared in the two respiratory rhythm conditions. rMSSD and SD1 were more reliable for recordings with ultra-short duration at all time intervals (r values from 0.764 to 0.950, p < 0.05) for spontaneous breathing condition, whereas the other indices require longer recording time to obtain reliable values. The controlled breathing rhythm evokes stronger r values for time domain indices (r values from 0.83 to 0.99, p < 0.05 for rMSSD), but impairs the mean values replicability of domains across most time intervals. Although the use of standardized breathing increases the correlations coefficients, all HRV indices showed an increase in mean values (t values from 3.79 to 14.94, p < 0.001) except the RR and HF that presented a decrease (t = 4.14 and 5.96, p < 0.0001). Our results indicate that proper ultra-short-term recording method can provide a quick and reliable source of cardiac autonomic nervous system assessment. © 2018 Wiley Periodicals, Inc.

The Cytoplasmic Tail of the T Cell Receptor CD3 ε Subunit Contains a Phospholipid-Binding Motif that Regulates T Cell Functions1

PubMed Central

DeFord-Watts, Laura M.; Tassin, Tara C.; Becker, Amy M.; Medeiros, Jennifer J.; Albanesi, Joseph P.; Love, Paul E.; Wülfing, Christoph; van Oers, Nicolai S. C.

2010-01-01

The CD3 ε subunit of the TCR complex contains two defined signaling domains, a proline-rich sequence and an ITAM. We identified a third signaling sequence in CD3 ε, termed the basic-rich stretch (BRS). Herein, we show that the positively charged residues of the BRS enable this region of CD3 ε to complex a subset of acidic phospholipids, including PI(3)P, PI(4)P, PI(5)P, PI(3,4,5)P3, and PI(4,5)P2. Transgenic mice containing mutations of the BRS exhibited varying developmental defects, ranging from reduced thymic cellularity to a complete block in T cell development. Peripheral T cells from BRS-modified mice also exhibited several defects, including decreased TCR surface expression, reduced TCR-mediated signaling responses to agonist peptide-loaded APCs, and delayed CD3 ε localization to the immunological synapse. Overall, these findings demonstrate a functional role for the CD3 ε lipid-binding domain in T cell biology. PMID:19542373

p63 threonine phosphorylation signals the interaction with the WW domain of the E3 ligase Itch

PubMed Central

Melino, Sonia; Bellomaria, Alessia; Nepravishta, Ridvan; Paci, Maurizio; Melino, Gerry

2014-01-01

Both in epithelial development as well as in epithelial cancers, the p53 family member p63 plays a crucial role acting as a master transcriptional regulator. P63 steady state protein levels are regulated by the E3 ubiquitin ligase Itch, via a physical interaction between the PPxY consensus sequence (PY motif) of p63 and one of the 4 WW domains of Itch; this substrate recognition process leads to protein-ubiquitylation and p63 proteasomal degradation. The interaction of the WW domains, a highly compact protein-protein binding module, with the short proline-rich sequences is therefore a crucial regulatory event that may offer innovative potential therapeutic opportunity. Previous molecular studies on the Itch-p63 recognition have been performed in vitro using the Itch-WW2 domain and the peptide interacting fragment of p63 (pep63), which includes the PY motif. Itch-WW2-pep63 interaction is also stabilized in vitro by the conformational constriction of the S-S cyclization in the p63 peptide. The PY motif of p63, as also for other proteins, is characterized by the nearby presence of a (T/S)P motif, which is a potential recognition site of the WW domain of the IV group present in the prolyl-isomerase Pin1. In this study, we demonstrate, by in silico and spectroscopical studies using both the linear pep63 and its cyclic form, that the threonine phosphorylation of the (T/S)PPPxY motif may represent a crucial regulatory event of the Itch-mediated p63 ubiquitylation, increasing the Itch-WW domains-p63 recognition event and stabilizing in vivo the Itch-WW-p63 complex. Moreover, our studies confirm that the subsequently trans/cis proline isomerization of (T/S)P motif by the Pin1 prolyl-isomerase, could modulate the E3-ligase interaction, and that the (T/S)pPtransPPxY motif represent the best conformer for the ItchWW-(T/S)PPPxY motif recognition. PMID:25485500

p63 threonine phosphorylation signals the interaction with the WW domain of the E3 ligase Itch.

PubMed

Melino, Sonia; Bellomaria, Alessia; Nepravishta, Ridvan; Paci, Maurizio; Melino, Gerry

2014-01-01

Both in epithelial development as well as in epithelial cancers, the p53 family member p63 plays a crucial role acting as a master transcriptional regulator. P63 steady state protein levels are regulated by the E3 ubiquitin ligase Itch, via a physical interaction between the PPxY consensus sequence (PY motif) of p63 and one of the 4 WW domains of Itch; this substrate recognition process leads to protein-ubiquitylation and p63 proteasomal degradation. The interaction of the WW domains, a highly compact protein-protein binding module, with the short proline-rich sequences is therefore a crucial regulatory event that may offer innovative potential therapeutic opportunity. Previous molecular studies on the Itch-p63 recognition have been performed in vitro using the Itch-WW2 domain and the peptide interacting fragment of p63 (pep63), which includes the PY motif. Itch-WW2-pep63 interaction is also stabilized in vitro by the conformational constriction of the S-S cyclization in the p63 peptide. The PY motif of p63, as also for other proteins, is characterized by the nearby presence of a (T/S)P motif, which is a potential recognition site of the WW domain of the IV group present in the prolyl-isomerase Pin1. In this study, we demonstrate, by in silico and spectroscopical studies using both the linear pep63 and its cyclic form, that the threonine phosphorylation of the (T/S)PPPxY motif may represent a crucial regulatory event of the Itch-mediated p63 ubiquitylation, increasing the Itch-WW domains-p63 recognition event and stabilizing in vivo the Itch-WW-p63 complex. Moreover, our studies confirm that the subsequently trans/cis proline isomerization of (T/S)P motif by the Pin1 prolyl-isomerase, could modulate the E3-ligase interaction, and that the (T/S)pPtransPPxY motif represent the best conformer for the ItchWW-(T/S)PPPxY motif recognition.

Human sweet taste receptor mediates acid-induced sweetness of miraculin

PubMed Central

Koizumi, Ayako; Tsuchiya, Asami; Nakajima, Ken-ichiro; Ito, Keisuke; Terada, Tohru; Shimizu-Ibuka, Akiko; Briand, Loïc; Asakura, Tomiko; Misaka, Takumi; Abe, Keiko

2011-01-01

Miraculin (MCL) is a homodimeric protein isolated from the red berries of Richadella dulcifica. MCL, although flat in taste at neutral pH, has taste-modifying activity to convert sour stimuli to sweetness. Once MCL is held on the tongue, strong sweetness is sensed over 1 h each time we taste a sour solution. Nevertheless, no molecular mechanism underlying the taste-modifying activity has been clarified. In this study, we succeeded in quantitatively evaluating the acid-induced sweetness of MCL using a cell-based assay system and found that MCL activated hT1R2-hT1R3 pH-dependently as the pH decreased from 6.5 to 4.8, and that the receptor activation occurred every time an acid solution was applied. Although MCL per se is sensory-inactive at pH 6.7 or higher, it suppressed the response of hT1R2-hT1R3 to other sweeteners at neutral pH and enhanced the response at weakly acidic pH. Using human/mouse chimeric receptors and molecular modeling, we revealed that the amino-terminal domain of hT1R2 is required for the response to MCL. Our data suggest that MCL binds hT1R2-hT1R3 as an antagonist at neutral pH and functionally changes into an agonist at acidic pH, and we conclude this may cause its taste-modifying activity. PMID:21949380

Research in Parallel Algorithms and Software for Computational Aerosciences

NASA Technical Reports Server (NTRS)

Domel, Neal D.

1996-01-01

Phase I is complete for the development of a Computational Fluid Dynamics parallel code with automatic grid generation and adaptation for the Euler analysis of flow over complex geometries. SPLITFLOW, an unstructured Cartesian grid code developed at Lockheed Martin Tactical Aircraft Systems, has been modified for a distributed memory/massively parallel computing environment. The parallel code is operational on an SGI network, Cray J90 and C90 vector machines, SGI Power Challenge, and Cray T3D and IBM SP2 massively parallel machines. Parallel Virtual Machine (PVM) is the message passing protocol for portability to various architectures. A domain decomposition technique was developed which enforces dynamic load balancing to improve solution speed and memory requirements. A host/node algorithm distributes the tasks. The solver parallelizes very well, and scales with the number of processors. Partially parallelized and non-parallelized tasks consume most of the wall clock time in a very fine grain environment. Timing comparisons on a Cray C90 demonstrate that Parallel SPLITFLOW runs 2.4 times faster on 8 processors than its non-parallel counterpart autotasked over 8 processors.

Research in Parallel Algorithms and Software for Computational Aerosciences

NASA Technical Reports Server (NTRS)

Domel, Neal D.

1996-01-01

Phase 1 is complete for the development of a computational fluid dynamics CFD) parallel code with automatic grid generation and adaptation for the Euler analysis of flow over complex geometries. SPLITFLOW, an unstructured Cartesian grid code developed at Lockheed Martin Tactical Aircraft Systems, has been modified for a distributed memory/massively parallel computing environment. The parallel code is operational on an SGI network, Cray J90 and C90 vector machines, SGI Power Challenge, and Cray T3D and IBM SP2 massively parallel machines. Parallel Virtual Machine (PVM) is the message passing protocol for portability to various architectures. A domain decomposition technique was developed which enforces dynamic load balancing to improve solution speed and memory requirements. A host/node algorithm distributes the tasks. The solver parallelizes very well, and scales with the number of processors. Partially parallelized and non-parallelized tasks consume most of the wall clock time in a very fine grain environment. Timing comparisons on a Cray C90 demonstrate that Parallel SPLITFLOW runs 2.4 times faster on 8 processors than its non-parallel counterpart autotasked over 8 processors.

Recombinant human B7.2 IgV-like domain expressed in bacteria maintains its co-stimulatory activity in vitro.

PubMed

Yan, Xiaocai; Ma, Jun; Zheng, Jin; Lai, Baochang; Geng, Yiping; Wang, Yili; Si, Lüsheng

2002-07-01

To investigate which of the two immunoglobulin (Ig)-like domains, the immunoglobulin variable region homologous domain IgV (hB7.2 IgV) and the immunoglobulin constant region homologous domain IgC (hB7.2 IgC) on the human B7.2 molecule contains receptor binding sites, and to evaluate whether the B7.2 protein expressed in bacteria has biological activity in vitro. Three fragments of hB7.2 IgV,hB7.2 IgC and the complete extracellular region of human B7.2 containing both the IgV and IgC domains,hB7.2 Ig (V+C), were amplified by PCR and subcloned into pGEM-Teasy. Three recombinants,pGEX-4T-3-hB7.2 IgV,pGEX-4T-3-hB7.2 IgC and pGEX-4T-3-hB7.2 Ig (V+C), were generated by cloning the fragments into a prokaryote expression plasmid (pGEX-4T-3) and transformed into the host strain E. coli DH5alpha. The relevant target fusion proteins consisting of GST and hB7.2 IgV,hB7.2 IgC and hB7.2 Ig (V+C), were identified by SDS-PAGE and Western blotting. With the presence of the first signal imitated by anti-CD3 antibody, T cell activation was observed by exposing purified T lymphocytes to each soluble form of the three bacterially-produced human B7.2 fusion proteins by [(3)H]-TdR incorporation. Three recombinant fusion proteins of human B7.2, GST-hB7.2 IgV, GST-hB7.2 IgC and GST-hB7.2 Ig (V+C) were produced and detected in inclusion body form from engineered bacteria. With the first signal present,T lymphocytes proliferated when co-stimulated by bacterially-produced either GST-hB7.2 Ig (V+C) or GST-hB7.2 IgV fusion proteins, but not by GST-hB7.2 IgC. Functional human B7.2 fusion protein can be produced in bacteria. The IgV-like domain of human B7.2 is sufficient for B7.2 to interact with its counter-receptors and co-stimulate T lymphocytes.

Stabilization of Foxp3 expression by CRISPR-dCas9-based epigenome editing in mouse primary T cells.

PubMed

Okada, Masahiro; Kanamori, Mitsuhiro; Someya, Kazue; Nakatsukasa, Hiroko; Yoshimura, Akihiko

2017-01-01

Epigenome editing is expected to manipulate transcription and cell fates and to elucidate the gene expression mechanisms in various cell types. For functional epigenome editing, assessing the chromatin context-dependent activity of artificial epigenetic modifier is required. In this study, we applied clustered regularly interspaced short palindromic repeats (CRISPR)-dCas9-based epigenome editing to mouse primary T cells, focusing on the Forkhead box P3 (Foxp3) gene locus, a master transcription factor of regulatory T cells (Tregs). The Foxp3 gene locus is regulated by combinatorial epigenetic modifications, which determine the Foxp3 expression. Foxp3 expression is unstable in transforming growth factor beta (TGF-β)-induced Tregs (iTregs), while stable in thymus-derived Tregs (tTregs). To stabilize Foxp3 expression in iTregs, we introduced dCas9-TET1CD (dCas9 fused to the catalytic domain (CD) of ten-eleven translocation dioxygenase 1 (TET1), methylcytosine dioxygenase) and dCas9-p300CD (dCas9 fused to the CD of p300, histone acetyltransferase) with guide RNAs (gRNAs) targeted to the Foxp3 gene locus. Although dCas9-TET1CD induced partial demethylation in enhancer region called conserved non-coding DNA sequences 2 (CNS2), robust Foxp3 stabilization was not observed. In contrast, dCas9-p300CD targeted to the promoter locus partly maintained Foxp3 transcription in cultured and primary T cells even under inflammatory conditions in vitro. Furthermore, dCas9-p300CD promoted expression of Treg signature genes and enhanced suppression activity in vitro. Our results showed that artificial epigenome editing modified the epigenetic status and gene expression of the targeted loci, and engineered cellular functions in conjunction with endogenous epigenetic modification, suggesting effective usage of these technologies, which help elucidate the relationship between chromatin states and gene expression.

Crystal structures of two Bordetella pertussis periplasmic receptors contribute to defining a novel pyroglutamic acid binding DctP subfamily.

PubMed

Rucktooa, Prakash; Antoine, Rudy; Herrou, Julien; Huvent, Isabelle; Locht, Camille; Jacob-Dubuisson, Françoise; Villeret, Vincent; Bompard, Coralie

2007-06-29

Gram-negative bacteria have developed several different transport systems for solute uptake. One of these, the tripartite ATP independent periplasmic transport system (TRAP-T), makes use of an extracytoplasmic solute receptor (ESR) which captures specific solutes with high affinity and transfers them to their partner permease complex located in the bacterial inner membrane. We hereby report the structures of DctP6 and DctP7, two such ESRs from Bordetella pertussis. These two proteins display a high degree of sequence and structural similarity and possess the "Venus flytrap" fold characteristic of ESRs, comprising two globular alpha/beta domains hinged together to form a ligand binding cleft. DctP6 and DctP7 both show a closed conformation due to the presence of one pyroglutamic acid molecule bound by highly conserved residues in their respective ligand binding sites. BLAST analyses have revealed that the DctP6 and DctP7 residues involved in ligand binding are strictly present in a number of predicted TRAP-T ESRs from other bacteria. In most cases, the genes encoding these TRAP-T systems are located in the vicinity of a gene coding for a pyroglutamic acid metabolising enzyme. Both the high degree of conservation of these ligand binding residues and the genomic context of these TRAP-T-coding operons in a number of bacterial species, suggest that DctP6 and DctP7 constitute the prototypes of a novel TRAP-T DctP subfamily involved in pyroglutamic acid transport.

Disruption of Neurexin 1 Associated with Autism Spectrum Disorder

PubMed Central

Kim, Hyung-Goo; Kishikawa, Shotaro; Higgins, Anne W.; Seong, Ihn-Sik; Donovan, Diana J.; Shen, Yiping; Lally, Eric; Weiss, Lauren A.; Najm, Juliane; Kutsche, Kerstin; Descartes, Maria; Holt, Lynn; Braddock, Stephen; Troxell, Robin; Kaplan, Lee; Volkmar, Fred; Klin, Ami; Tsatsanis, Katherine; Harris, David J.; Noens, Ilse; Pauls, David L.; Daly, Mark J.; MacDonald, Marcy E.; Morton, Cynthia C.; Quade, Bradley J.; Gusella, James F.

2008-01-01

Autism is a neurodevelopmental disorder of complex etiology in which genetic factors play a major role. We have implicated the neurexin 1 (NRXN1) gene in two independent subjects who display an autism spectrum disorder (ASD) in association with a balanced chromosomal abnormality involving 2p16.3. In the first, with karyotype 46,XX,ins(16;2)(q22.1;p16.1p16.3)pat, NRXN1 is directly disrupted within intron 5. Importantly, the father possesses the same chromosomal abnormality in the absence of ASD, indicating that the interruption of α-NRXN1 is not fully penetrant and must interact with other factors to produce ASD. The breakpoint in the second subject, with 46,XY,t(1;2)(q31.3;p16.3)dn, occurs ∼750 kb 5′ to NRXN1 within a 2.6 Mb genomic segment that harbors no currently annotated genes. A scan of the NRXN1 coding sequence in a cohort of ASD subjects, relative to non-ASD controls, revealed that amino acid alterations in neurexin 1 are not present at high frequency in ASD. However, a number of rare sequence variants in the coding region, including two missense changes in conserved residues of the α-neurexin 1 leader sequence and of an epidermal growth factor (EGF)-like domain, respectively, suggest that even subtle changes in NRXN1 might contribute to susceptibility to ASD. PMID:18179900

Molecular Evolution of Aminoacyl tRNA Synthetase Proteins in the Early History of Life

NASA Astrophysics Data System (ADS)

Fournier, Gregory P.; Andam, Cheryl P.; Alm, Eric J.; Gogarten, J. Peter

2011-12-01

Aminoacyl-tRNA synthetases (aaRS) consist of several families of functionally conserved proteins essential for translation and protein synthesis. Like nearly all components of the translation machinery, most aaRS families are universally distributed across cellular life, being inherited from the time of the Last Universal Common Ancestor (LUCA). However, unlike the rest of the translation machinery, aaRS have undergone numerous ancient horizontal gene transfers, with several independent events detected between domains, and some possibly involving lineages diverging before the time of LUCA. These transfers reveal the complexity of molecular evolution at this early time, and the chimeric nature of genomes within cells that gave rise to the major domains. Additionally, given the role of these protein families in defining the amino acids used for protein synthesis, sequence reconstruction of their pre-LUCA ancestors can reveal the evolutionary processes at work in the origin of the genetic code. In particular, sequence reconstructions of the paralog ancestors of isoleucyl- and valyl- RS provide strong empirical evidence that at least for this divergence, the genetic code did not co-evolve with the aaRSs; rather, both amino acids were already part of the genetic code before their cognate aaRSs diverged from their common ancestor. The implications of this observation for the early evolution of RNA-directed protein biosynthesis are discussed.

CoCoNuT: General relativistic hydrodynamics code with dynamical space-time evolution

NASA Astrophysics Data System (ADS)

Dimmelmeier, Harald; Novak, Jérôme; Cerdá-Durán, Pablo

2012-02-01

CoCoNuT is a general relativistic hydrodynamics code with dynamical space-time evolution. The main aim of this numerical code is the study of several astrophysical scenarios in which general relativity can play an important role, namely the collapse of rapidly rotating stellar cores and the evolution of isolated neutron stars. The code has two flavors: CoCoA, the axisymmetric (2D) magnetized version, and CoCoNuT, the 3D non-magnetized version.

An Atmospheric General Circulation Model with Chemistry for the CRAY T3E: Design, Performance Optimization and Coupling to an Ocean Model

NASA Technical Reports Server (NTRS)

Farrara, John D.; Drummond, Leroy A.; Mechoso, Carlos R.; Spahr, Joseph A.

1998-01-01

The design, implementation and performance optimization on the CRAY T3E of an atmospheric general circulation model (AGCM) which includes the transport of, and chemical reactions among, an arbitrary number of constituents is reviewed. The parallel implementation is based on a two-dimensional (longitude and latitude) data domain decomposition. Initial optimization efforts centered on minimizing the impact of substantial static and weakly-dynamic load imbalances among processors through load redistribution schemes. Recent optimization efforts have centered on single-node optimization. Strategies employed include loop unrolling, both manually and through the compiler, the use of an optimized assembler-code library for special function calls, and restructuring of parts of the code to improve data locality. Data exchanges and synchronizations involved in coupling different data-distributed models can account for a significant fraction of the running time. Therefore, the required scattering and gathering of data must be optimized. In systems such as the T3E, there is much more aggregate bandwidth in the total system than in any particular processor. This suggests a distributed design. The design and implementation of a such distributed 'Data Broker' as a means to efficiently couple the components of our climate system model is described.

tRNA-derived short RNAs bind to Saccharomyces cerevisiae ribosomes in a stress-dependent manner and inhibit protein synthesis in vitro

PubMed Central

Kasprzyk, Marta; Twardowski, Tomasz

2016-01-01

Recently, a number of ribosome-associated non-coding RNAs (rancRNAs) have been discovered in all three domains of life. In our previous studies, we have described several types of rancRNAs in Saccharomyces cerevisiae, derived from many cellular RNAs, including mRNAs, rRNAs, tRNAs and snoRNAs. Here, we present the evidence that the tRNA fragments from simple eukaryotic organism S. cerevisiae directly bind to the ribosomes. Interestingly, rancRNA-tRFs in yeast are derived from both, 5′- and 3′-part of the tRNAs and both types of tRFs associate with the ribosomes in vitro. The location of tRFs within the ribosomes is distinct from classical A- and P-tRNA binding sites. Moreover, 3′-tRFs bind to the distinct site than 5′-tRFs. These interactions are stress dependent and as a consequence, provoke regulation of protein biosynthesis. We observe strong correlation between tRF binding to the ribosomes and inhibition of protein biosynthesis in particular environmental conditions. These results implicate the existence of an ancient and conserved mechanism of translation regulation with the involvement of ribosome-associating tRNA-derived fragments. PMID:27609601

Creating and facilitating change for Person-Centred Coordinated Care (P3C): The development of the Organisational Change Tool (P3C-OCT).

PubMed

Horrell, Jane; Lloyd, Helen; Sugavanam, Thavapriya; Close, James; Byng, Richard

2018-04-01

Person Centred Coordinated Care (P3C) is a UK priority for patients, carers, professionals, commissioners and policy makers. Services are developing a range of approaches to deliver this care with a lack of tools to guide implementation. A scoping review and critical examination of current policy, key literature and NHS guidelines, together with stakeholder involvement led to the identification of domains, subdomains and component activities (processes and behaviours) required to deliver P3C. These were validated through codesign with stakeholders via a series of workshops and cognitive interviews. Six core domains of P3C were identified as follows: (i) my goals, (ii) care planning, (iii) transitions, (iv) decision making (v), information and communication and (vi) organizational support activities. These were populated by 29 core subdomains (question items). A number of response codes (components) to each question provide examples of the processes and activities that can be actioned to achieve each core subdomain of P3C. The P3C-OCT provides a coherent approach to monitoring progress and supporting practice development towards P3C. It can be used to generate a shared understanding of the core domains of P3C at a service delivery level, and support reorganization of care for those with complex needs. The tool can reliably detect change over time, as demonstrated in a sample of 40 UK general practices. It is currently being used in four UK evaluations of new models of care and being further developed as a training tool for the delivery of P3C. © 2017 The Authors Health Expectations Published by John Wiley & Sons Ltd.

ATHENA 3D: A finite element code for ultrasonic wave propagation

NASA Astrophysics Data System (ADS)

Rose, C.; Rupin, F.; Fouquet, T.; Chassignole, B.

2014-04-01

The understanding of wave propagation phenomena requires use of robust numerical models. 3D finite element (FE) models are generally prohibitively time consuming. However, advances in computing processor speed and memory allow them to be more and more competitive. In this context, EDF R&D developed the 3D version of the well-validated FE code ATHENA2D. The code is dedicated to the simulation of wave propagation in all kinds of elastic media and in particular, heterogeneous and anisotropic materials like welds. It is based on solving elastodynamic equations in the calculation zone expressed in terms of stress and particle velocities. The particularity of the code relies on the fact that the discretization of the calculation domain uses a Cartesian regular 3D mesh while the defect of complex geometry can be described using a separate (2D) mesh using the fictitious domains method. This allows combining the rapidity of regular meshes computation with the capability of modelling arbitrary shaped defects. Furthermore, the calculation domain is discretized with a quasi-explicit time evolution scheme. Thereby only local linear systems of small size have to be solved. The final step to reduce the computation time relies on the fact that ATHENA3D has been parallelized and adapted to the use of HPC resources. In this paper, the validation of the 3D FE model is discussed. A cross-validation of ATHENA 3D and CIVA is proposed for several inspection configurations. The performances in terms of calculation time are also presented in the cases of both local computer and computation cluster use.

Specific and Modular Binding Code for Cytosine Recognition in Pumilio/FBF (PUF) RNA-binding Domains

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

Dong, Shuyun; Wang, Yang; Cassidy-Amstutz, Caleb

2011-10-28

Pumilio/fem-3 mRNA-binding factor (PUF) proteins possess a recognition code for bases A, U, and G, allowing designed RNA sequence specificity of their modular Pumilio (PUM) repeats. However, recognition side chains in a PUM repeat for cytosine are unknown. Here we report identification of a cytosine-recognition code by screening random amino acid combinations at conserved RNA recognition positions using a yeast three-hybrid system. This C-recognition code is specific and modular as specificity can be transferred to different positions in the RNA recognition sequence. A crystal structure of a modified PUF domain reveals specific contacts between an arginine side chain and themore » cytosine base. We applied the C-recognition code to design PUF domains that recognize targets with multiple cytosines and to generate engineered splicing factors that modulate alternative splicing. Finally, we identified a divergent yeast PUF protein, Nop9p, that may recognize natural target RNAs with cytosine. This work deepens our understanding of natural PUF protein target recognition and expands the ability to engineer PUF domains to recognize any RNA sequence.« less

Structure of the hepatitis E virus-like particle suggests mechanisms for virus assembly and receptor binding

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

Guu, Tom S.Y.; Liu, Zheng; Ye, Qiaozhen

Hepatitis E virus (HEV), a small, non-enveloped RNA virus in the family Hepeviridae, is associated with endemic and epidemic acute viral hepatitis in developing countries. Our 3.5-{angstrom} structure of a HEV-like particle (VLP) shows that each capsid protein contains 3 linear domains that form distinct structural elements: S, the continuous capsid; P1, 3-fold protrusions; and P2, 2-fold spikes. The S domain adopts a jelly-roll fold commonly observed in small RNA viruses. The P1 and P2 domains both adopt {beta}-barrel folds. Each domain possesses a potential polysaccharide-binding site that may function in cell-receptor binding. Sugar binding to P1 at the capsidmore » protein interface may lead to capsid disassembly and cell entry. Structural modeling indicates that native T = 3 capsid contains flat dimers, with less curvature than those of T = 1 VLP. Our findings significantly advance the understanding of HEV molecular biology and have application to the development of vaccines and antiviral medications.« less

Analysis of variable sites between two complete South China tiger (Panthera tigris amoyensis) mitochondrial genomes.

PubMed

Zhang, Wenping; Yue, Bisong; Wang, Xiaofang; Zhang, Xiuyue; Xie, Zhong; Liu, Nonglin; Fu, Wenyuan; Yuan, Yaohua; Chen, Daqing; Fu, Danghua; Zhao, Bo; Yin, Yuzhong; Yan, Xiahui; Wang, Xinjing; Zhang, Rongying; Liu, Jie; Li, Maoping; Tang, Yao; Hou, Rong; Zhang, Zhihe

2011-10-01

In order to investigate the mitochondrial genome of Panthera tigris amoyensis, two South China tigers (P25 and P27) were analyzed following 15 cymt-specific primer sets. The entire mtDNA sequence was found to be 16,957 bp and 17,001 bp long for P25 and P27 respectively, and this difference in length between P25 and P27 occurred in the number of tandem repeats in the RS-3 segment of the control region. The structural characteristics of complete P. t. amoyensis mitochondrial genomes were also highly similar to those of P. uncia. Additionally, the rate of point mutation was only 0.3% and a total of 59 variable sites between P25 and P27 were found. Out of the 59 variable sites, 6 were located in 6 different tRNA genes, 6 in the 2 rRNA genes, 7 in non-coding regions (one located between tRNA-Asn and tRNA-Tyr and six in the D-loop), and 40 in 10 protein-coding genes. COI held the largest amount of variable sites (9 sites) and Cytb contained the highest variable rate (0.7%) in the complete sequences. Moreover, out of the 40 variable sites located in 10 protein-coding genes, 12 sites were nonsynonymous.

Coupled anisotropic and isotropic tomography of the upper mantle beneath northern Fennoscandia - Application of a novel code AniTomo

NASA Astrophysics Data System (ADS)

Munzarova, Helena; Plomerova, Jaroslava; Kissling, Edi; Vecsey, Ludek; Babuska, Vladislav

2017-04-01

Seismological investigations of the continental mantle lithosphere, particularly its anisotropic structure, advance our understanding of plate tectonics and formation of continents. Orientation of the anisotropic fabrics reflects stress fields during the lithosphere origin and its later deformations. To contribute to studies of the large-scale upper-mantle anisotropy, we have developed code AniTomo for regional anisotropic tomography. AniTomo allows a simultaneous inversion of relative travel time residuals of teleseismic P waves for 3D distribution of isotropic-velocity perturbations and anisotropy in the upper mantle. Weak hexagonal anisotropy with symmetry axis oriented generally in 3D is assumed. The code was successfully tested on a large series of synthetic datasets and synthetic structures. In this contribution we present results of the first application of novel code AniTomo to real data, i.e., relative travel-time residuals of teleseismic P waves recorded during passive seismic experiment LAPNET in the northern Fennoscandia between 2007 and 2009. The region of Fennoscandia is a suitable choice for the first application of the new code. This Precambrian region is tectonically stable and has a thick anisotropic mantle lithosphere (Plomerova and Babuska, Lithos 2010) without significant thermal heterogeneities. In the resulting anisotropic model of the upper mantle beneath the northern Fennoscandia, the strongest anisotropy and the largest velocity perturbations concentrate in the mantle lithosphere. We delimit regions of laterally and vertically consistent anisotropy in the mantle-lithospheric part of the model. In general, the identified anisotropic regions correspond to domains detected by joint interpretation of lateral variations of the P- and SKS-wave anisotropic parameters (Plomerova et al., Solid Earth 2011). Particularly, the mantle lithosphere in the western part of the volume studied exhibits a distinct and uniform fabric that is sharply separated from the surrounding regions. The eastern boundary of this region gradually shifts westward with increasing depth in the tomographic model. We connect the retrieved domain-like anisotropic structure of the mantle lithosphere in the northern Fennoscandia with preserved fossil fabrics of the Archean micro-plates, accreted during the Precambrian orogenic processes.

Phosphorylation of the Grb2- and phosphatidylinositol 3-kinase p85-binding p36/38 by Syk in Lck-negative T cells.

PubMed

von Willebrand, M; Williams, S; Tailor, P; Mustelin, T

1998-06-01

Activation of the mitogen-activated protein kinase (MAPK) pathway by the T-cell antigen receptor (TCR) in T cells involves a positive role for phosphatidylinositol 3-kinase (PI3K) activity. We recently reported that over-expression of the Syk protein tyrosine kinase in the Lck-negative JCaM1 cells enabled the TCR to induce a normal activation of the Erk2 MAPK and enhanced transcription of a reporter gene driven by the nuclear factor of activated T cells and AP-1. Because this system allows us to analyse the targets for Syk in receptor-mediated signalling, we examined the role of PI3K in signalling events between the TCR-regulated Syk and the downstream activation of Erk2. We report that inhibition of PI3K by wortmannin or an inhibitory p85 construct, p85deltaiSH2, reduced the TCR-induced Syk-dependent activation of Erk2, as well as the appearance of phospho-Erk and phospho-Mek. At the same time, expression of Syk resulted in the activation-dependent phosphorylation of three proteins that bound to the src homology 2 (SH2) domains of PI3K p85. The strongest of these bands had an apparent molecular mass of 36-38 kDa on SDS gels, and it was quantitatively removed from the lysates by adsorption to a fusion protein containing the SH2 domain of Grb2. The appearance of this band was Syk dependent, and it was seen only upon triggering of the TCR complex. Thus, p36/38 was phosphorylated by Syk or a Syk-regulated kinase, and this protein may provide a link to the recruitment and activation of PI3K, as well as to the Ras-MAPK pathway, in TCR-triggered T cells.

Three-dimensional reconstructions of the bacteriophage CUS-3 virion reveal a conserved coat protein I-domain but a distinct tailspike receptor-binding domain

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

Parent, Kristin N., E-mail: kparent@msu.edu; Tang, Jinghua; Cardone, Giovanni

CUS-3 is a short-tailed, dsDNA bacteriophage that infects serotype K1 Escherichia coli. We report icosahedrally averaged and asymmetric, three-dimensional, cryo-electron microscopic reconstructions of the CUS-3 virion. Its coat protein structure adopts the “HK97-fold” shared by other tailed phages and is quite similar to that in phages P22 and Sf6 despite only weak amino acid sequence similarity. In addition, these coat proteins share a unique extra external domain (“I-domain”), suggesting that the group of P22-like phages has evolved over a very long time period without acquiring a new coat protein gene from another phage group. On the other hand, the morphologymore » of the CUS-3 tailspike differs significantly from that of P22 or Sf6, but is similar to the tailspike of phage K1F, a member of the extremely distantly related T7 group of phages. We conclude that CUS-3 obtained its tailspike gene from a distantly related phage quite recently. - Highlights: • Asymmetric and symmetric three-dimensional reconstructions of phage CUS-3 are presented. • CUS-3 major capsid protein has a conserved I-domain, which is found in all three categories of “P22-like phage”. • CUS-3 has very different tailspike receptor binding domain from those of P22 and Sf6. • The CUS-3 tailspike likely was acquired by horizontal gene transfer.« less

Nonlinear diffusion equations as asymptotic limits of Cahn-Hilliard systems on unbounded domains via Cauchy's criterion

NASA Astrophysics Data System (ADS)

Fukao, Takeshi; Kurima, Shunsuke; Yokota, Tomomi

2018-05-01

This paper develops an abstract theory for subdifferential operators to give existence and uniqueness of solutions to the initial-boundary problem (P) for the nonlinear diffusion equation in an unbounded domain $\\Omega\\subset\\mathbb{R}^N$ ($N\\in{\\mathbb N}$), written as \\[ \\frac{\\partial u}{\\partial t} + (-\\Delta+1)\\beta(u) = g \\quad \\mbox{in}\\ \\Omega\\times(0, T), \\] which represents the porous media, the fast diffusion equations, etc., where $\\beta$ is a single-valued maximal monotone function on $\\mathbb{R}$, and $T>0$. Existence and uniqueness for (P) were directly proved under a growth condition for $\\beta$ even though the Stefan problem was excluded from examples of (P). This paper completely removes the growth condition for $\\beta$ by confirming Cauchy's criterion for solutions of the following approximate problem (P)$_{\\varepsilon}$ with approximate parameter $\\varepsilon>0$: \\[ \\frac{\\partial u_{\\varepsilon}}{\\partial t} + (-\\Delta+1)(\\varepsilon(-\\Delta+1)u_{\\varepsilon} + \\beta(u_{\\varepsilon}) + \\pi_{\\varepsilon}(u_{\\varepsilon})) = g \\quad \\mbox{in}\\ \\Omega\\times(0, T), \\] which is called the Cahn--Hilliard system, even if $\\Omega \\subset \\mathbb{R}^N$ ($N \\in \\mathbb{N}$) is an unbounded domain. Moreover, it can be seen that the Stefan problem is covered in the framework of this paper.

The Optimal Convergence Rate of the p-Version of the Finite Element Method.

DTIC Science & Technology

1985-10-01

commercial and research codes. The p-version and h-p versions are new developments. There is only one commercial code, the system PROBE ( Noetic Tech, St...Louis). The theoretical aspects have been studied only recently. The first theoretical paper appeared in 1981 (see [7)). See also [1), [7], [81, [9...model problem (2.2) (2.3) is a classical case of the elliptic equation problem on a nonsmooth domain. The structure of this problem is well studied

Screening for rare variants in the PNPLA3 gene in obese liver biopsy patients.

PubMed

Zegers, Doreen; Verrijken, An; Francque, Sven; de Freitas, Fenna; Beckers, Sigri; Aerts, Evi; Ruppert, Martin; Hubens, Guy; Michielsen, Peter; Van Hul, Wim; Van Gaal, Luc F

2016-12-01

Previous research has clearly implicated the PNPLA3 gene in the etiology of nonalcoholic fatty liver disease as a polymorphism in the gene was found to be robustly associated to the disease. However, data on the involvement of rare PNPLA3 variants in the development of nonalcoholic fatty liver disease (NAFLD) is currently limited. Therefore, we performed an extensive mutation analysis study on a cohort of obese liver biopsy patients to determine PNPLA3 variation and its correlation with fatty liver disease. We screened the entire coding region of the PNPLA3 gene in DNA samples of 393 obese liver biopsy patients with varying degrees of fatty liver disease. Mutation analysis was performed by high-resolution melting curve analysis in combination with direct sequencing. We identified several common polymorphisms as well as one rare synonymous variant (c.867G>A rs139896256), one rare intronic variant (c.979+13C>T) and 3 nonsynonymous coding variants (p.A76T, p.A104V and p.T200M) in the PNPLA3 gene. In silico analysis indicated that the p.A104V variant will probably have no functional effect, whereas for the p.A76T and p.T200M variant a possible pathogenic effect is suggested. Overall, we showed that novel variants in PNPLA3 are very rare in our liver biopsy cohort, thereby indicating that their impact on the etiology of NAFLD is probably limited. Nevertheless, for the three rare coding variants that were identified in patients with advanced liver disease, further functional characterization will be essential to verify their potential disease causality. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Type-specific and cross-reactive antibodies and T cell responses in norovirus VLP immunized mice are targeted both to conserved and variable domains of capsid VP1 protein.

PubMed

Malm, Maria; Tamminen, Kirsi; Vesikari, Timo; Blazevic, Vesna

2016-10-01

Norovirus (NoV)-specific antibodies, which block binding of the virus-like particles (VLPs) to the cell receptors are conformation dependent and directed towards the most exposed domain of the NoV capsid VP1 protein, the P2 domain. Limited data are available on the antibodies directed to other domains of the VP1, and even less on the NoV VP1-specific T cell epitopes. In here, BALB/c mice were immunized with six VLPs derived from NoV GII.4-1999, GII.4-2009 (New Orleans), GII.4-2012 (Sydney), GII.12, GI.1, and G1.3. Serum immunoglobulin G binding antibodies, histo-blood group antigen blocking antibodies and T cell responses using type-specific and heterologous NoV VLPs, P-dimers and 76 overlapping synthetic peptides, spanning the entire 539 amino acid sequence of GII.4 VP1, were determined. The results showed that at least half of the total antibody content is directed towards conserved S domain of the VP1. Only a small fraction (<1%) of the VP1 binding antibodies were blocking/neutralizing. With the use of matrix peptide pools and individual peptides, seven CD4 + and CD8 + T cell restricted epitopes were mapped, two located in S domain, four in P2 domain and one in P1 domain of NoV VP1. The epitopes were GII.4 strain-specific but also common GII.4 genotype-specific T cell epitopes were identified. More importantly, the results suggest a 9-amino acids long sequence ( 318 PAPLGTPDF 326 ) in P2 domain of VP1 as a universal NoV genogroup II-specific CD8 + T cell epitope. Distribution of the T cell epitopes alongside the capsid VP1 indicates the need of the complete protein for high immunogenicity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Casp8p41 generated by HIV protease kills CD4 T cells through direct Bak activation

PubMed Central

Sainski, Amy M.; Dai, Haiming; Natesampillai, Sekar; Pang, Yuan-Ping; Bren, Gary D.; Cummins, Nathan W.; Correia, Cristina; Meng, X. Wei; Tarara, James E.; Ramirez-Alvarado, Marina; Katzmann, David J.; Ochsenbauer, Christina; Kappes, John C.

2014-01-01

Previous studies have shown that human immunodeficiency virus (HIV) protease cleaves procaspase 8 to a fragment, termed Casp8p41, that lacks caspase activity but nonetheless contributes to T cell apoptosis. Herein, we show that Casp8p41 contains a domain that interacts with the BH3-binding groove of pro-apoptotic Bak to cause Bak oligomerization, Bak-mediated membrane permeabilization, and cell death. Levels of active Bak are higher in HIV-infected T cells that express Casp8p41. Conversely, targeted mutations in the Bak-interacting domain diminish Bak binding and Casp8p41-mediated cell death. Similar mutations in procaspase 8 impair the ability of HIV to kill infected T cells. These observations support a novel paradigm in which HIV converts a normal cellular constituent into a direct activator that functions like a BH3-only protein. PMID:25246614

Gene fusions AHRR-NCOA2, NCOA2-ETV4, ETV4-AHRR, P4HA2-TBCK, and TBCK-P4HA2 resulting from the translocations t(5;8;17)(p15;q13;q21) and t(4;5)(q24;q31) in a soft tissue angiofibroma

PubMed Central

Panagopoulos, Ioannis; Gorunova, Ludmila; Viset, Trond; Heim, Sverre

2016-01-01

We present an angiofibroma of soft tissue with the karyotype 46,XY,t(4;5)(q24;q31),t(5;8;17)(p15;q13;q21) [8]/46,XY,t(1;14)(p31;q32)[2]/46,XY[3]. RNA-sequencing showed that the t(4;5)(q24;q31) resulted in recombination of the genes TBCK on 4q24 and P4HA2 on 5q31.1 with generation of an in-frame TBCK-P4HA2 and the reciprocal but out-of-frame P4HA2-TBCK fusion transcripts. The putative TBCK-P4HA2 protein would contain the kinase, the rhodanese-like domain, and the Tre-2/Bub2/Cdc16 (TBC) domains of TBCK together with the P4HA2 protein which is a component of the prolyl 4-hydroxylase. The t(5;8;17)(p15;q13;q21) three-way chromosomal translocation targeted AHRR (on 5p15), NCOA2 (on 8q13), and ETV4 (on 17q21) generating the in-frame fusions AHRR-NCOA2 and NCOA2-ETV4 as well as an out-of-frame ETV4-AHRR transcript. In the AHRR-NCOA2 protein, the C-terminal part of AHRR is replaced by the C-terminal part of NCOA2 which contains two activation domains. The NCOA2-ETV4 protein would contain the helix-loop-helix, PAS_9 and PAS_11, CITED domains, the SRC-1 domain of NCOA2 and the ETS DNA-binding domain of ETV4. No fusion gene corresponding to t(1;14)(p31;q32) was found. Our findings indicate that, in spite of the recurrence of AHRR-NCOA2 in angiofibroma of soft tissue, additional genetic events (or fusion genes) might be required for the development of this tumor. PMID:27633981

Gene fusions AHRR-NCOA2, NCOA2-ETV4, ETV4-AHRR, P4HA2-TBCK, and TBCK-P4HA2 resulting from the translocations t(5;8;17)(p15;q13;q21) and t(4;5)(q24;q31) in a soft tissue angiofibroma.

PubMed

Panagopoulos, Ioannis; Gorunova, Ludmila; Viset, Trond; Heim, Sverre

2016-11-01

We present an angiofibroma of soft tissue with the karyotype 46,XY,t(4;5)(q24;q31),t(5;8;17)(p15;q13;q21)[8]/46,XY,t(1;14)(p31;q32)[2]/46,XY[3]. RNA‑sequencing showed that the t(4;5)(q24;q31) resulted in recombination of the genes TBCK on 4q24 and P4HA2 on 5q31.1 with generation of an in‑frame TBCK‑P4HA2 and the reciprocal but out‑of‑frame P4HA2‑TBCK fusion transcripts. The putative TBCK‑P4HA2 protein would contain the kinase, the rhodanese‑like domain, and the Tre‑2/Bub2/Cdc16 (TBC) domains of TBCK together with the P4HA2 protein which is a component of the prolyl 4‑hydroxylase. The t(5;8;17)(p15;q13;q21) three‑way chromosomal translocation targeted AHRR (on 5p15), NCOA2 (on 8q13), and ETV4 (on 17q21) generating the in‑frame fusions AHRR‑NCOA2 and NCOA2‑ETV4 as well as an out‑of‑frame ETV4‑AHRR transcript. In the AHRR‑NCOA2 protein, the C‑terminal part of AHRR is replaced by the C‑terminal part of NCOA2 which contains two activation domains. The NCOA2‑ETV4 protein would contain the helix‑loop‑helix, PAS_9 and PAS_11, CITED domains, the SRC‑1 domain of NCOA2 and the ETS DNA‑binding domain of ETV4. No fusion gene corresponding to t(1;14)(p31;q32) was found. Our findings indicate that, in spite of the recurrence of AHRR‑NCOA2 in angiofibroma of soft tissue, additional genetic events (or fusion genes) might be required for the development of this tumor.

Moving from Batch to Field Using the RT3D Reactive Transport Modeling System

NASA Astrophysics Data System (ADS)

Clement, T. P.; Gautam, T. R.

2002-12-01

The public domain reactive transport code RT3D (Clement, 1997) is a general-purpose numerical code for solving coupled, multi-species reactive transport in saturated groundwater systems. The code uses MODFLOW to simulate flow and several modules of MT3DMS to simulate the advection and dispersion processes. RT3D employs the operator-split strategy which allows the code solve the coupled reactive transport problem in a modular fashion. The coupling between reaction and transport is defined through a separate module where the reaction equations are specified. The code supports a versatile user-defined reaction option that allows users to define their own reaction system through a Fortran-90 subroutine, known as the RT3D-reaction package. Further a utility code, known as BATCHRXN, allows the users to independently test and debug their reaction package. To analyze a new reaction system at a batch scale, users should first run BATCHRXN to test the ability of their reaction package to model the batch data. After testing, the reaction package can simply be ported to the RT3D environment to study the model response under 1-, 2-, or 3-dimensional transport conditions. This paper presents example problems that demonstrate the methods for moving from batch to field-scale simulations using BATCHRXN and RT3D codes. The first example describes a simple first-order reaction system for simulating the sequential degradation of Tetrachloroethene (PCE) and its daughter products. The second example uses a relatively complex reaction system for describing the multiple degradation pathways of Tetrachloroethane (PCA) and its daughter products. References 1) Clement, T.P, RT3D - A modular computer code for simulating reactive multi-species transport in 3-Dimensional groundwater aquifers, Battelle Pacific Northwest National Laboratory Research Report, PNNL-SA-28967, September, 1997. Available at: http://bioprocess.pnl.gov/rt3d.htm.

Simulating The Prompt Electromagnetic Pulse In 3D Using Vector Spherical Harmonics

NASA Astrophysics Data System (ADS)

Friedman, Alex; Cohen, Bruce I.; Eng, Chester D.; Farmer, William A.; Grote, David P.; Kruger, Hans W.; Larson, David J.

2017-10-01

We describe a new, efficient code for simulating the prompt electromagnetic pulse. In SHEMP (``Spherical Harmonic EMP''), we extend to 3-D the methods pioneered in C. Longmire's CHAP code. The geomagnetic field and air density are consistent with CHAP's assumed spherical symmetry only for narrow domains of influence about the line of sight, limiting validity to very early times. Also, we seek to model inherently 3-D situations. In CHAP and our own CHAP-lite, the independent coordinates are r (the distance from the source) and τ = t-r/c; the pulse varies slowly with r at fixed τ, so a coarse radial grid suffices. We add non-spherically-symmetric physics via a vector spherical harmonic decomposition. For each (l,m) harmonic, the radial equation is similar to that in CHAP and CHAP-lite. We present our methodology and results on model problems. This work was performed under the auspices of the U.S. DOE by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

Toward a practical template-based approach to semiquantitative SPECT myocardial perfusion imaging.

PubMed

Hughes, Tyler; Celler, Anna

2012-03-01

Our template-based quantitative perfusion single photon emission computed tomography (SPECT) method (T-QPS) performs semiquantitative analysis for myocardial perfusion imaging (MPI) without the use of normal databases. However, in its current form, T-QPS requires extensive calculations, which limits its clinical application. In the interest of clinical feasibility, the authors examine the trade-off between accuracy and processing time as the method is simplified. The T-QPS method uses the reconstructed SPECT image of the patient to create a 3D digital template of his∕her healthy heart. This template is then projected, reconstructed, and sampled into the bulls-eye map domain. A ratio of the patient and template images produces a final corrected image in which a threshold is applied to identify perfusion defects. In principle, the template should be constructed with the heart and all extracardiac activity, and the projection step should include primary and scatter components; however, this leads to lengthy calculations. In an attempt to shorten the processing time, the authors analyzed the performance of four template (T) generation methods: T(P-HRT), T(PS-HRT), T(P-HRTBKG), and T(PS-HRTBKG), where P and S represent primary and scattered photons included in the projection step, respectively; and HRT and HRTBKG represent template constructed with the heart only and the heart with background activity, respectively. Forty-eight thorax phantoms and 21 randomly selected patient studies were analyzed using each approach. All studies used GE's Infinia Hawkeye SPECT∕CT system and followed a standard cardiac acquisition protocol. Approximate processing times for the T(P-HRT), T(PS-HRT), T(P-HRTBKG), and T(PS-HRTBKG) methods were less than a minute, 2-3 h, less than a minute and 3-4 h, respectively. In both the simulation and patient studies, a significant reduction in the quality of perfusion defect definition was exhibited by the T(P-HRT) method relative to the other three methods. The optimal method with respect to perfusion defect definition and processing time was T(P-HRTBKG) with a sensitivity, specificity, and accuracy in spatially defining the perfusion defects (simulation study) of 80%, 84%, and 83%, respectively. The T-QPS method using T(P-HRTBKG) leads to accurate and fast semiquantitative analysis of SPECT MPI, without the use of normal databases.

Evaluating health information technology: provider satisfaction with an HIV-specific, electronic clinical management and reporting system.

PubMed

Magnus, Manya; Herwehe, Jane; Andrews, Laura; Gibson, Laura; Daigrepont, Nathan; De Leon, Jordana M; Hyslop, Newton E; Styron, Steven; Wilcox, Ronald; Kaiser, Michael; Butler, Michael K

2009-02-01

Health information technology (HIT) offers the potential to improve care for persons living with HIV. Provider satisfaction with HIT is essential to realize benefits, yet its evaluation presents challenges. An HIV-specific, electronic clinical management and reporting system was implemented in Louisiana's eight HIV clinics, serving over 7500. A serial cross-sectional survey was administered at three points between April 2002 and July 2005; qualitative methods were used to augment quantitative. Multivariable methods were used to characterize provider satisfaction. The majority of the sample (n = 196; T1 = 105; T2 = 46; T3 = 45) was female (80.0%), between ages of 25 and 50 years (68.3%), frequent providers at that clinic (53.7% more than 4 days per week), and had been at the same clinic for a year or more (85.0%). Improvements in satisfaction were observed in patient tracking ( p < 0.05), distribution of educational materials ( p < 0.04), and belief that electronic systems improve care ( p < 0.05). Provider self-reports of time to complete critical functions decreased for all tasks, two significantly so. Time (in minutes) to find current CD4 count decreased at each time point (mean 3.9 [standard deviation {SD} 5.8], 2.9 [2.3], 2.1 [2.6], p>0.05), current viral load decreased at each time point (mean 4.0 [SD 5.6], 2.9 [2.5], 1.8 [2.6], p = 0.08], current antiretroviral status decreased at each time point (mean 3.9 [SD 4.7], 2.9 [3.7], 1.5 [1.1], p < 0.04), history of antiretroviral use decreased at each time point (mean 15.1 [SD 21.9], 6.0 [5.4], 5.4 [7.2], p < 0.04]. Time savings were realized, averaging 16.1 minutes per visit ( p < 0.04). Providers were satisfied with HIT in multiple domains, and significant time savings were realized.

User's manual for three dimensional FDTD version D code for scattering from frequency-dependent dielectric and magnetic materials

NASA Technical Reports Server (NTRS)

Beggs, John H.; Luebbers, Raymond J.; Kunz, Karl S.

1992-01-01

The Penn State Finite Difference Time Domain Electromagnetic Scattering Code version D is a 3-D numerical electromagnetic scattering code based upon the finite difference time domain technique (FDTD). The manual provides a description of the code and corresponding results for several scattering problems. The manual is organized into 14 sections: introduction; description of the FDTD method; operation; resource requirements; version D code capabilities; a brief description of the default scattering geometry; a brief description of each subroutine; a description of the include file; a section briefly discussing Radar Cross Section computations; a section discussing some scattering results; a sample problem setup section; a new problem checklist; references and figure titles. The FDTD technique models transient electromagnetic scattering and interactions with objects of arbitrary shape and/or material composition. In the FDTD method, Maxwell's curl equations are discretized in time-space and all derivatives (temporal and spatial) are approximated by central differences.

Truncated ALK derived from chromosomal translocation t(2;5)(p23;q35) binds to the SH3 domain of p85-PI3K.

PubMed

Polgar, Doris; Leisser, Christina; Maier, Susanne; Strasser, Stephan; Rüger, Beate; Dettke, Markus; Khorchide, Maya; Simonitsch, Ingrid; Cerni, Christa; Krupitza, Georg

2005-02-15

The chromosomal translocation t(2;5)(p23;q35) is associated with "Anaplastic large cell lymphomas" (ALCL), a Non Hodgkin Lymphoma occurring in childhood. The fusion of the tyrosine kinase gene-ALK (anaplastic lymphoma kinase) on chromosome 2p23 to the NPM (nucleophosmin/B23) gene on chromosome 5q35 results in a 80 kDa chimeric protein, which activates the "survival" kinase PI3K. However, the binding mechanism between truncated ALK and PI3K is poorly understood. Therefore, we attempted to elucidate the molecular interaction between ALK and the regulatory p85 subunit of PI3K. Here we provide evidence that the truncated ALK homodimer binds to the SH3 domain of p85. This finding may be useful for the development of a new target-specific intervention.

The Carboxyl Terminus of v-Abl Protein Can Augment SH2 Domain Function

PubMed Central

Warren, David; Heilpern, Andrew J.; Berg, Kent; Rosenberg, Naomi

2000-01-01

Abelson murine leukemia virus (Ab-MLV) transforms NIH 3T3 and pre-B cells via expression of the v-Abl tyrosine kinase. Although the enzymatic activity of this molecule is absolutely required for transformation, other regions of the protein are also important for this response. Among these are the SH2 domain, involved in phosphotyrosine-dependent protein-protein interactions, and the long carboxyl terminus, which plays an important role in transformation of hematopoietic cells. Important signals are sent from each of these regions, and transformation is most likely orchestrated by the concerted action of these different parts of the protein. To explore this idea, we compared the ability of the v-Src SH2 domain to substitute for that of v-Abl in the full-length P120 v-Abl protein and in P70 v-Abl, a protein that lacks the carboxyl terminus characteristic of Abl family members. Ab-MLV strains expressing P70/S2 failed to transform NIH 3T3 cells and demonstrated a greatly reduced capacity to mediate signaling events associated with the Ras-dependent mitogen-activated protein (MAP) kinase pathway. In contrast, Ab-MLV strains expressing P120/S2 were indistinguishable from P120 with respect to these features. Analyses of additional mutants demonstrated that the last 162 amino acids of the carboxyl terminus were sufficient to restore transformation. These data demonstrate that an SH2 domain with v-Abl substrate specificity is required for NIH 3T3 transformation in the absence of the carboxyl terminus and suggest that cooperativity between the extreme carboxyl terminus and the SH2 domain facilitates the transmission of transforming signals via the MAP kinase pathway. PMID:10775585

Assessment of corneal epithelial thickness in dry eye patients.

PubMed

Cui, Xinhan; Hong, Jiaxu; Wang, Fei; Deng, Sophie X; Yang, Yujing; Zhu, Xiaoyu; Wu, Dan; Zhao, Yujin; Xu, Jianjiang

2014-12-01

To investigate the features of corneal epithelial thickness topography with Fourier-domain optical coherence tomography (OCT) in dry eye patients. In this cross-sectional study, 100 symptomatic dry eye patients and 35 normal subjects were enrolled. All participants answered the ocular surface disease index questionnaire and were subjected to OCT, corneal fluorescein staining, tear breakup time, Schirmer 1 test without anesthetic (S1t), and meibomian morphology. Several epithelium statistics for each eye, including central, superior, inferior, minimum, maximum, minimum - maximum, and map standard deviation, were averaged. Correlations of epithelial thickness with the symptoms of dry eye were calculated. The mean (±SD) central, superior, and inferior corneal epithelial thickness was 53.57 (±3.31) μm, 52.00 (±3.39) μm, and 53.03 (±3.67) μm in normal eyes and 52.71 (±2.83) μm, 50.58 (±3.44) μm, and 52.53 (±3.36) μm in dry eyes, respectively. The superior corneal epithelium was thinner in dry eye patients compared with normal subjects (p = 0.037), whereas central and inferior epithelium were not statistically different. In the dry eye group, patients with higher severity grades had thinner superior (p = 0.017) and minimum (p < 0.001) epithelial thickness, more wide range (p = 0.032), and greater deviation (p = 0.003). The average central epithelial thickness had no correlation with tear breakup time, S1t, or the severity of meibomian glands, whereas average superior epithelial thickness positively correlated with S1t (r = 0.238, p = 0.017). Fourier-domain OCT demonstrated that the thickness map of the dry eye corneal epithelium was thinner than normal eyes in the superior region. In more severe dry eye disease patients, the superior and minimum epithelium was much thinner, with a greater range of map standard deviation.

Phosphorylation of PPP(S/T)P motif of the free LRP6 intracellular domain is not required to activate the Wnt/beta-catenin pathway and attenuate GSK3beta activity.

PubMed

Beagle, Brandon; Mi, Kaihong; Johnson, Gail V W

2009-11-01

The canonical Wnt/beta-catenin signaling pathway plays a critical role in numerous physiological and pathological processes. LRP6 is an essential co-receptor for Wnt/beta-catenin signaling; as transduction of the Wnt signal is strongly dependent upon GSK3beta-mediated phosphorylation of multiple PPP(S/T)P motifs within the membrane-anchored LRP6 intracellular domain. Previously, we showed that the free LRP6 intracellular domain (LRP6-ICD) can activate the Wnt/beta-catenin pathway in a beta-catenin and TCF/LEF-1 dependent manner, as well as interact with and attenuate GSK3beta activity. However, it is unknown if the ability of LRP6-ICD to attenuate GSK3beta activity and modulate activation of the Wnt/beta-catenin pathway requires phosphorylation of the LRP6-ICD PPP(S/T)P motifs, in a manner similar to the membrane-anchored LRP6 intracellular domain. Here we provide evidence that the LRP6-ICD does not have to be phosphorylated at its PPP(S/T)P motif by GSK3beta to stabilize endogenous cytosolic beta-catenin resulting in activation of TCF/LEF-1 and the Wnt/beta-catenin pathway. LRP6-ICD and a mutant in which all 5 PPP(S/T)P motifs were changed to PPP(A)P motifs equivalently interacted with and attenuated GSK3beta activity in vitro, and both constructs inhibited the in situ GSK3beta-mediated phosphorylation of beta-catenin and tau to the same extent. These data indicate that the LRP6-ICD attenuates GSK3beta activity similar to other GSK3beta binding proteins, and is not a result of it being a GSK3beta substrate. Our findings suggest the functional and regulatory mechanisms governing the free LRP6-ICD may be distinct from membrane-anchored LRP6, and that release of the LRP6-ICD may provide a complimentary signaling cascade capable of modulating Wnt-dependent gene expression. (c) 2009 Wiley-Liss, Inc.

A novel potential/viscous flow coupling technique for computing helicopter flow fields

NASA Technical Reports Server (NTRS)

Summa, J. Michael; Strash, Daniel J.; Yoo, Sungyul

1993-01-01

The primary objective of this work was to demonstrate the feasibility of a new potential/viscous flow coupling procedure for reducing computational effort while maintaining solution accuracy. This closed-loop, overlapped velocity-coupling concept has been developed in a new two-dimensional code, ZAP2D (Zonal Aerodynamics Program - 2D), a three-dimensional code for wing analysis, ZAP3D (Zonal Aerodynamics Program - 3D), and a three-dimensional code for isolated helicopter rotors in hover, ZAPR3D (Zonal Aerodynamics Program for Rotors - 3D). Comparisons with large domain ARC3D solutions and with experimental data for a NACA 0012 airfoil have shown that the required domain size can be reduced to a few tenths of a percent chord for the low Mach and low angle of attack cases and to less than 2-5 chords for the high Mach and high angle of attack cases while maintaining solution accuracies to within a few percent. This represents CPU time reductions by a factor of 2-4 compared with ARC2D. The current ZAP3D calculation for a rectangular plan-form wing of aspect ratio 5 with an outer domain radius of about 1.2 chords represents a speed-up in CPU time over the ARC3D large domain calculation by about a factor of 2.5 while maintaining solution accuracies to within a few percent. A ZAPR3D simulation for a two-bladed rotor in hover with a reduced grid domain of about two chord lengths was able to capture the wake effects and compared accurately with the experimental pressure data. Further development is required in order to substantiate the promise of computational improvements due to the ZAPR3D coupling concept.

Pinning, rotation, and metastability of BiFeO 3 cycloidal domains in a magnetic field

DOE PAGES

Fishman, Randy S.

2018-01-03

Earlier models for the room-temperature multiferroic BiFeO 3 implicitly assumed that a very strong anisotropy restricts the domain wave vectors q to the threefold-symmetric axis normal to the static polarization P. However, recent measurements demonstrate that the domain wave vectors q rotate within the hexagonal plane normal to P away from the magnetic field orientation m. In this paper, we show that the previously neglected threefold anisotropy K 3 restricts the wave vectors to lie along the threefold axis in zero field. Taking m to lie along a threefold axis, the domain with q parallel to m remains metastable belowmore » B c1≈7 T. Due to the pinning of domains by nonmagnetic impurities, the wave vectors of the other two domains start to rotate away from m above 5.6 T, when the component of the torque τ=M×B along P exceeds a threshold value τ pin. Since τ=0 when m⊥q, the wave vectors of those domains never become completely perpendicular to the magnetic field. Our results explain recent measurements of the critical field as a function of field orientation, small-angle neutron scattering measurements of the wave vectors, as well as spectroscopic measurements with m along a threefold axis. Finally, the model developed in this paper also explains how the three multiferroic domains of BiFeO 3 for a fixed P can be manipulated by a magnetic field.« less

Pinning, rotation, and metastability of BiFeO3 cycloidal domains in a magnetic field

NASA Astrophysics Data System (ADS)

Fishman, Randy S.

2018-01-01

Earlier models for the room-temperature multiferroic BiFeO3 implicitly assumed that a very strong anisotropy restricts the domain wave vectors q to the threefold-symmetric axis normal to the static polarization P . However, recent measurements demonstrate that the domain wave vectors q rotate within the hexagonal plane normal to P away from the magnetic field orientation m . We show that the previously neglected threefold anisotropy K3 restricts the wave vectors to lie along the threefold axis in zero field. Taking m to lie along a threefold axis, the domain with q parallel to m remains metastable below Bc 1≈7 T. Due to the pinning of domains by nonmagnetic impurities, the wave vectors of the other two domains start to rotate away from m above 5.6 T, when the component of the torque τ =M ×B along P exceeds a threshold value τpin. Since τ =0 when m ⊥q , the wave vectors of those domains never become completely perpendicular to the magnetic field. Our results explain recent measurements of the critical field as a function of field orientation, small-angle neutron scattering measurements of the wave vectors, as well as spectroscopic measurements with m along a threefold axis. The model developed in this paper also explains how the three multiferroic domains of BiFeO3 for a fixed P can be manipulated by a magnetic field.

Pinning, rotation, and metastability of BiFeO 3 cycloidal domains in a magnetic field

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

Fishman, Randy S.

Earlier models for the room-temperature multiferroic BiFeO 3 implicitly assumed that a very strong anisotropy restricts the domain wave vectors q to the threefold-symmetric axis normal to the static polarization P. However, recent measurements demonstrate that the domain wave vectors q rotate within the hexagonal plane normal to P away from the magnetic field orientation m. In this paper, we show that the previously neglected threefold anisotropy K 3 restricts the wave vectors to lie along the threefold axis in zero field. Taking m to lie along a threefold axis, the domain with q parallel to m remains metastable belowmore » B c1≈7 T. Due to the pinning of domains by nonmagnetic impurities, the wave vectors of the other two domains start to rotate away from m above 5.6 T, when the component of the torque τ=M×B along P exceeds a threshold value τ pin. Since τ=0 when m⊥q, the wave vectors of those domains never become completely perpendicular to the magnetic field. Our results explain recent measurements of the critical field as a function of field orientation, small-angle neutron scattering measurements of the wave vectors, as well as spectroscopic measurements with m along a threefold axis. Finally, the model developed in this paper also explains how the three multiferroic domains of BiFeO 3 for a fixed P can be manipulated by a magnetic field.« less

[Reducing maternal parenting stress of children with autism spectrum disorder: father's involvement].

PubMed

Hu, C C; Li, Y; Zhou, B R; Liu, C X; Li, C Y; Zhang, Y; Xu, Q; Xu, X

2017-05-04

Objective: To explore the relationship between fathers' nursing time and maternal parenting stress of children with autism spectrum disorder(ASD). Method: Mothers of 98 ASD children who were first diagnosed in the department of Child Health Care, Children's Hospital of Fudan University during June 2015 to January 2016 were included in the ASD group, with mothers of 92 typical children from a Community Maternal and Child Health Hospital and a kindergarten in the control group. The evaluation of parenting stress, parents' nursing time and other related factors were cross-sectionally analyzed. Interview was conducted with the following tools: Parental Stress Index-Short Form(PSI-SF)for maternal parenting stress, and self-made General Parenting Information Questionnaire for nursing time of both parents and other related factors. The relationships were analyzed by Multiple Linear Regression analysis and Wilcoxon Rank-Sum test. Result: Maternal parenting stress of ASD children had a significant negative correlation with father's nursing time in total score of parenting stress, PCDI domain and PD domain ( t =-2.76, -2.98, -2.79; P =0.007, 0.004, 0.006), within which PD domain also included family annual income and mothers' nursing time ( R (2)=0.22, 0.24, 0.25); while no such correlation was found in control group in terms of father's nursing time( P =0.22, 0.42, 0.06). Wilcoxon Rank-Sum test showed that in 62 (63.3%) double-income ASD families and 72(78.3%) double-income typical families, there were significant differences between ASD fathers' and ASD mothers'and typical fathers'nursing time(2.0(0.5, 2.1) vs . 3.5(2.4, 6.0) vs . 3.0(2.0, 4.7)h, t =-86.32、-49.65, all P <0.01). Conclusion: Lack of fathers' involvements was common in ASD children's families. Increasing these fathers' nursing time, as well as their enthusiasm and initiative in the family intervention could relieve maternal parenting stress and improve the intervention pattern of ASD children.

Directed evolution of the forkhead-associated domain to generate anti-phosphospecific reagents by phage-display

PubMed Central

Pershad, Kritika; Wypisniak, Karolina; Kay, Brian K.

2012-01-01

While affinity reagents are valuable tools for monitoring protein phosphorylation and studying signaling events in cells, generating them through immunization of animals with phosphopeptides is expensive, laborious and time consuming. An attractive alternative is to use protein evolution techniques and isolate new anti-phosphopeptide binding specificities from a library of variants of a phosphopeptide-binding domain. To explore this strategy, we attempted to display on the surface of bacteriophage M13, the N-terminal Forkhead-associated domain (FHA1) of yeast Rad53p, which is a naturally occurring phosphothreonine (pT)-binding domain, and found it to be non-functional due to misfolding in the bacterial periplasm. To overcome this limitation, a library of FHA1 variants was constructed by mutagenic PCR and functional variants were isolated after three rounds of affinity selection with its pT peptide ligand. A hydrophobic residue at position 34 in the β1-strand was discovered to be essential for phage-display of a functional FHA1 domain. Additionally, by heating the phage library to 50°C prior to affinity selection with its cognate pT peptide, we identified a variant (G2) that was ~8°C more thermal stable than the wild-type domain. Using G2 as a scaffold, we constructed phage-displayed libraries of FHA1 variants and affinity selected for variants that bound selectively to five pT peptides. These reagents are renewable and have high protein yields (~20–25 mg/L), when expressed in Escherichia coli. Thus, we have changed the specificity of the FHA1 domain and demonstrated that engineering phosphopeptide-binding domains is an attractive avenue for generating new anti-phosphopeptide binding specificities in vitro by phage-display. PMID:22985966

Directed evolution of the forkhead-associated domain to generate anti-phosphospecific reagents by phage display.

PubMed

Pershad, Kritika; Wypisniak, Karolina; Kay, Brian K

2012-11-23

While affinity reagents are valuable tools for monitoring protein phosphorylation and studying signaling events in cells, generating them through immunization of animals with phosphopeptides is expensive, laborious, and time-consuming. An attractive alternative is to use protein evolution techniques and isolate new anti-phosphopeptide binding specificities from a library of variants of a phosphopeptide-binding domain. To explore this strategy, we attempted to display on the surface of bacteriophage M13 the N-terminal Forkhead-associated (FHA1) domain of yeast Rad53p, which is a naturally occurring phosphothreonine (pT)-binding domain, and found it to be nonfunctional due to misfolding in the bacterial periplasm. To overcome this limitation, we constructed a library of FHA1 variants by mutagenic PCR and isolated functional variants after three rounds of affinity selection with its pT peptide ligand. A hydrophobic residue at position 34 in the β1 strand was discovered to be essential for phage display of a functional FHA1 domain. Additionally, by heating the phage library to 50°C prior to affinity selection with its cognate pT peptide, we identified a variant (G2) that was ~8°C more thermally stable than the wild-type domain. Using G2 as a scaffold, we constructed phage-displayed libraries of FHA1 variants and affinity selected for variants that bound selectively to five pT peptides. These reagents are renewable and have high protein yields (~20-25mg/L), when expressed in Escherichia coli. Thus, we have changed the specificity of the FHA1 domain and demonstrated that engineering phosphopeptide-binding domains is an attractive avenue for generating new anti-phosphopeptide binding specificities in vitro by phage display. Copyright © 2012 Elsevier Ltd. All rights reserved.

Advanced propeller noise prediction in the time domain

NASA Technical Reports Server (NTRS)

Farassat, F.; Dunn, M. H.; Spence, P. L.

1992-01-01

The time domain code ASSPIN gives acousticians a powerful technique of advanced propeller noise prediction. Except for nonlinear effects, the code uses exact solutions of the Ffowcs Williams-Hawkings equation with exact blade geometry and kinematics. By including nonaxial inflow, periodic loading noise, and adaptive time steps to accelerate computer execution, the development of this code becomes complete.

Frequency- and Time-Domain Methods in Soil-Structure Interaction Analysis

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

Bolisetti, Chandrakanth; Whittaker, Andrew S.; Coleman, Justin L.

2015-06-01

Soil-structure interaction (SSI) analysis in the nuclear industry is currently performed using linear codes that function in the frequency domain. There is a consensus that these frequency-domain codes give reasonably accurate results for low-intensity ground motions that result in almost linear response. For higher intensity ground motions, which may result in nonlinear response in the soil, structure or at the vicinity of the foundation, the adequacy of frequency-domain codes is unproven. Nonlinear analysis, which is only possible in the time domain, is theoretically more appropriate in such cases. These methods are available but are rarely used due to the largemore » computational requirements and a lack of experience with analysts and regulators. This paper presents an assessment of the linear frequency-domain code, SASSI, which is widely used in the nuclear industry, and the time-domain commercial finite-element code, LS-DYNA, for SSI analysis. The assessment involves benchmarking the SSI analysis procedure in LS-DYNA against SASSI for linearly elastic models. After affirming that SASSI and LS-DYNA result in almost identical responses for these models, they are used to perform nonlinear SSI analyses of two structures founded on soft soil. An examination of the results shows that, in spite of using identical material properties, the predictions of frequency- and time-domain codes are significantly different in the presence of nonlinear behavior such as gapping and sliding of the foundation.« less

Hypercube matrix computation task

NASA Technical Reports Server (NTRS)

Calalo, Ruel H.; Imbriale, William A.; Jacobi, Nathan; Liewer, Paulett C.; Lockhart, Thomas G.; Lyzenga, Gregory A.; Lyons, James R.; Manshadi, Farzin; Patterson, Jean E.

1988-01-01

A major objective of the Hypercube Matrix Computation effort at the Jet Propulsion Laboratory (JPL) is to investigate the applicability of a parallel computing architecture to the solution of large-scale electromagnetic scattering problems. Three scattering analysis codes are being implemented and assessed on a JPL/California Institute of Technology (Caltech) Mark 3 Hypercube. The codes, which utilize different underlying algorithms, give a means of evaluating the general applicability of this parallel architecture. The three analysis codes being implemented are a frequency domain method of moments code, a time domain finite difference code, and a frequency domain finite elements code. These analysis capabilities are being integrated into an electromagnetics interactive analysis workstation which can serve as a design tool for the construction of antennas and other radiating or scattering structures. The first two years of work on the Hypercube Matrix Computation effort is summarized. It includes both new developments and results as well as work previously reported in the Hypercube Matrix Computation Task: Final Report for 1986 to 1987 (JPL Publication 87-18).

Mutational analysis in a patient with a variant form of Gaucher disease caused by SAP-2 deficiency

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

Rafi, M.A.; Gala, G. de; Xunling Zhang

1993-01-01

It is now clear that the lysosomal hydrolysis of sphingolipids requires both lysosomal enzymes and so-called sphingolipid activator proteins (SAPs). One gene, called prosaposin, codes for a precursor protein that is proteolytically cut into four putative SAPs. These four SAPs, of about 80 amino acids, share some structural features but differ somewhat in their specificity. Domain 3 of prosaposin mRNA contains the coding region for SAP-2, an activator of glucocerebrosidase. While most patients with Gaucher disease store glucosylceramide due to defects in glucocerebrosidase, a few patients store this lipid in the presence of normal enzyme levels. In this paper themore » authors describe the identification of a point mutation in domain 3 of a patient who died with this variant form of Gaucher disease. Polymerase chain reaction amplification was performed in the small amount of genomic DNA available using primers generated from the intronic sequence surrounding domain 3. The patient was found to have a T-to-G substitution at position 1144 (counting from the A of ATG initiation codon) in half of the M13 recombinant clones. This changes the codon for cysteine[sub 382] to glycine. His father and unaffected brother also had this mutation, but his mother did not. She was found to have half of the normal amount of mRNA for prosaposin in her cultured skin fibroblasts. Therefore, this child inherited a point mutation in domain 3 from his father and a deficiency of all four SAPs coded for by prosaposin from his mother. 29 refs., 3 figs., 1 tab.« less

Relationship of autonomic imbalance and circadian disruption with obesity and type 2 diabetes in resistant hypertensive patients

PubMed Central

2011-01-01

Background Hypertension, diabetes and obesity are not isolated findings, but a series of interacting interactive physiologic derangements. Taking into account genetic background and lifestyle behavior, AI (autonomic imbalance) could be a common root for RHTN (resistant hypertension) or RHTN plus type 2 diabetes (T2D) comorbidity development. Moreover, circadian disruption can lead to metabolic and vasomotor impairments such as obesity, insulin resistance and resistant hypertension. In order to better understand the triggered emergence of obesity and T2D comorbidity in resistant hypertension, we investigated the pattern of autonomic activity in the circadian rhythm in RHTN with and without type 2 diabetes (T2D), and its relationship with serum adiponectin concentration. Methods Twenty five RHTN patients (15 non-T2D and 10 T2D, 15 males, 10 females; age range 34 to 70 years) were evaluated using the following parameters: BMI (body mass index), biochemical analysis, serum adiponectinemia, echocardiogram and ambulatory electrocardiograph heart rate variability (HRV) in time and frequency domains stratified into three periods: 24 hour, day time and night time. Results Both groups demonstrated similar characteristics despite of the laboratory analysis concerning T2D like fasting glucose, HbA1c levels and hypertriglyceridemia. Both groups also revealed disruption of the circadian rhythm: inverted sympathetic and parasympathetic tones during day (parasympathetic > sympathetic tone) and night periods (sympathetic > parasympathetic tone). T2D group had increased BMI and serum triglyceride levels (mean 33.7 ± 4.0 vs 26.6 ± 3.7 kg/m2 - p = 0.00; 254.8 ± 226.4 vs 108.6 ± 48.7 mg/dL - p = 0.04), lower levels of adiponectin (6729.7 ± 3381.5 vs 10911.5 ± 5554.0 ng/mL - p = 0.04) and greater autonomic imbalance evaluated by HRV parameters in time domain compared to non-T2D RHTN patients. Total patients had HRV correlated positively with serum adiponectin (r = 0.37 [95% CI -0.04 - 1.00] p = 0.03), negatively with HbA1c levels (r = -0.58 [95% CI -1.00 - -0.3] p = 0.00) and also adiponectin correlated negatively with HbA1c levels (r = -0.40 [95% CI -1.00 - -0.07] p = 0.02). Conclusion Type 2 diabetes comorbidity is associated with greater autonomic imbalance, lower adiponectin levels and greater BMI in RHTN patients. Similar circadian disruption was also found in both groups indicating the importance of lifestyle behavior in the genesis of RHTN. PMID:21426540

Federal Logistics Information System (FLIS). Volume 18. Automated Mailing Labels System (AMLS) FLIS Procedures Manual

DTIC Science & Technology

1993-07-01

LPLPW3t TIME XXXX\\ LISI ADDRESSES AND DISIRIBUTION FOR XX XXXXXXXXXXXXXXXXXX\\ LSER ID XXX P %G[ ZZ.zz9 AA MLG MAILING ADDRESS ZIP CODE PI C x XNXX XX...4100.39-M Volume Is APPENDIX C AMLS INFORMATIONAL MESSAGES Corrective Action: Press the F6 ( COM MIT) function key to add the Distribution information

Piecemeal Buildup of the Genetic Code, Ribosomes, and Genomes from Primordial tRNA Building Blocks

PubMed Central

Caetano-Anollés, Derek; Caetano-Anollés, Gustavo

2016-01-01

The origin of biomolecular machinery likely centered around an ancient and central molecule capable of interacting with emergent macromolecular complexity. tRNA is the oldest and most central nucleic acid molecule of the cell. Its co-evolutionary interactions with aminoacyl-tRNA synthetase protein enzymes define the specificities of the genetic code and those with the ribosome their accurate biosynthetic interpretation. Phylogenetic approaches that focus on molecular structure allow reconstruction of evolutionary timelines that describe the history of RNA and protein structural domains. Here we review phylogenomic analyses that reconstruct the early history of the synthetase enzymes and the ribosome, their interactions with RNA, and the inception of amino acid charging and codon specificities in tRNA that are responsible for the genetic code. We also trace the age of domains and tRNA onto ancient tRNA homologies that were recently identified in rRNA. Our findings reveal a timeline of recruitment of tRNA building blocks for the formation of a functional ribosome, which holds both the biocatalytic functions of protein biosynthesis and the ability to store genetic memory in primordial RNA genomic templates. PMID:27918435

Piecemeal Buildup of the Genetic Code, Ribosomes, and Genomes from Primordial tRNA Building Blocks.

PubMed

Caetano-Anollés, Derek; Caetano-Anollés, Gustavo

2016-12-02

The origin of biomolecular machinery likely centered around an ancient and central molecule capable of interacting with emergent macromolecular complexity. tRNA is the oldest and most central nucleic acid molecule of the cell. Its co-evolutionary interactions with aminoacyl-tRNA synthetase protein enzymes define the specificities of the genetic code and those with the ribosome their accurate biosynthetic interpretation. Phylogenetic approaches that focus on molecular structure allow reconstruction of evolutionary timelines that describe the history of RNA and protein structural domains. Here we review phylogenomic analyses that reconstruct the early history of the synthetase enzymes and the ribosome, their interactions with RNA, and the inception of amino acid charging and codon specificities in tRNA that are responsible for the genetic code. We also trace the age of domains and tRNA onto ancient tRNA homologies that were recently identified in rRNA. Our findings reveal a timeline of recruitment of tRNA building blocks for the formation of a functional ribosome, which holds both the biocatalytic functions of protein biosynthesis and the ability to store genetic memory in primordial RNA genomic templates.

Domain structure of the ribozyme from eubacterial ribonuclease P.

PubMed Central

Loria, A; Pan, T

1996-01-01

Large RNAs can be composed of discrete domains that fold independently. One such "folding domain" has been identified previously in the ribozyme from Bacillus subtilis ribonuclease P (denoted P RNA). This domain contains roughly one-third of all residues. Folding of an RNA construct consisting of the remaining two-thirds of B. subtilis P RNA was examined by Fe(II)-EDTA hydroxyl radical protection. This molecule folds into the proper higher-order structure under identical conditions as the full-length P RNA, suggesting the presence of a second folding domain in B. subtilis P RNA. Folding analysis of the Escherichia coli P RNA by hydroxyl radical protection shows that this P RNA is completely folded at 5-6 mM Mg2+. In order to analyze the structural organization of folding domains in E. coli P RNA, constructs were designed based on the domain structure of B. subtilis P RNA. Fe(II)-EDTA protection indicates that E. coli P RNA also contains two folding domains. Despite the significant differences at the secondary structure level, both P RNAs appear to converge structurally at the folding domain level. The pre-tRNA substrate, localized in previous studies, may bind across the folding domains with the acceptor stem/3'CCA contacting the domain including the active site and the T stem-loop contacting the other. Because all eubacterial P RNAs share considerable homology in secondary structure to either B. subtilis or E. coli P RNA, these results suggest that this domain structure may be applicable for most, if not all, eubacterial P RNAs. Identification of folding domains should be valuable in dissecting structure-function relationship of large RNAs. PMID:8718684

Activation of PI3K/Akt signaling by n-terminal SH2 domain mutants of the p85α regulatory subunit of PI3K is enhanced by deletion of its c-terminal SH2 domain.

PubMed

Hofmann, Bianca T; Jücker, Manfred

2012-10-01

The phosphoinositide 3-kinase (PI3K) is frequently activated in human cancer cells due to gain of function mutations in the catalytic (p110) and the regulatory (p85) subunits. The regulatory subunit consists of an SH3 domain and two SH2 domains. An oncogenic form of p85α named p65 lacking the c-terminal SH2 domain (cSH2) has been cloned from an irradiation-induced murine thymic lymphoma and transgenic mice expressing p65 in T lymphocytes develop a lymphoproliferative disorder. We have recently detected a c-terminal truncated form of p85α named p76α in a human lymphoma cell line lacking most of the cSH2 domain due to a frame shift mutation. Here, we report that the deletion of the cSH2 domain enhances the activating effects of the n-terminal SH2 domain (nSH2) mutants K379E and R340E on the PI3K/Akt pathway and micro tumor formation in a focus assay. Further analysis revealed that this transforming effect is mediated by activation of the catalytic PI3K isoform p110α and downstream signaling through mTOR. Our data further support a mechanistic model in which mutations of the cSH2 domain of p85α can abrogate its negative regulatory function on PI3K activity via the nSH2 domain of p85α. Copyright © 2012 Elsevier Inc. All rights reserved.

Coding SNP in tenascin-C Fn-III-D domain associates with adult asthma.

PubMed

Matsuda, Akira; Hirota, Tomomitsu; Akahoshi, Mitsuteru; Shimizu, Makiko; Tamari, Mayumi; Miyatake, Akihiko; Takahashi, Atsushi; Nakashima, Kazuko; Takahashi, Naomi; Obara, Kazuhiko; Yuyama, Noriko; Doi, Satoru; Kamogawa, Yumiko; Enomoto, Tadao; Ohshima, Koichi; Tsunoda, Tatsuhiko; Miyatake, Shoichiro; Fujita, Kimie; Kusakabe, Moriaki; Izuhara, Kenji; Nakamura, Yusuke; Hopkin, Julian; Shirakawa, Taro

2005-10-01

The extracellular matrix glycoprotein tenascin-C (TNC) has been accepted as a valuable histopathological subepithelial marker for evaluating the severity of asthmatic disease and the therapeutic response to drugs. We found an association between an adult asthma and an SNP encoding TNC fibronectin type III-D (Fn-III-D) domain in a case-control study between a Japanese population including 446 adult asthmatic patients and 658 normal healthy controls. The SNP (44513A/T in exon 17) strongly associates with adult bronchial asthma (chi2 test, P=0.00019, Odds ratio=1.76, 95% confidence interval=1.31-2.36). This coding SNP induces an amino acid substitution (Leu1677Ile) within the Fn-III-D domain of the alternative splicing region. Computer-assisted protein structure modeling suggests that the substituted amino acid locates at the outer edge of the beta-sheet in Fn-III-D domain and causes instability of this beta-sheet. As the TNC fibronectin-III domain has molecular elasticity, the structural change may affect the integrity and stiffness of asthmatic airways. In addition, TNC expression in lung fibroblasts increases with Th2 immune cytokine stimulation. Thus, Leu1677Ile may be valuable marker for evaluating the risk for developing asthma and plays a role in its pathogenesis.

Effects of mutations within the SV40 large T antigen ATPase/p53 binding domain on viral replication and transformation.

PubMed

Peden, K W; Srinivasan, A; Vartikar, J V; Pipas, J M

1998-01-01

The simian virus 40 (SV40) large T antigen is a 708 amino-acid protein possessing multiple biochemical activities that play distinct roles in productive infection or virus-induced cell transformation. The carboxy-terminal portion of T antigen includes a domain that carries the nucleotide binding and ATPase activities of the protein, as well as sequences required for T antigen to associate with the cellular tumor suppressor p53. Consequently this domain functions both in viral DNA replication and cellular transformation. We have generated a collection of SV40 mutants with amino-acid deletions, insertions or substitutions in specific domains of the protein. Here we report the properties of nine mutants with single or multiple substitutions between amino acids 402 and 430, a region thought to be important for both the p53 binding and ATPase functions. The mutants were examined for the ability to produce infectious progeny virions, replicate viral DNA in vivo, perform in trans complementation tests, and transform established cell lines. Two of the mutants exhibited a wild-type phenotype in all these tests. The remaining seven mutants were defective for plaque formation and viral DNA replication, but in each case these defects could be complemented by a wild-type T antigen supplied in trans. One of these replication-defective mutants efficiently transformed the REF52 and C3H10T1/2 cell lines as assessed by the dense-focus assay. The remaining six mutants were defective for transforming REF52 cells and transformed the C3H10T1/2 line with a reduced efficiency. The ability of mutant T antigen to transform REF52 cells correlated with their ability to induce increased levels of p53.

Applying Frequency-Domain Equalization to Code-Division Multiple Access and Transform-Domain Communications Systems

DTIC Science & Technology

2008-03-01

terms the last time we spoke, I can say without a doubt that he was my favorite cousin. You are both missed, always.... I want to thank my wife for her...IEEE Communications Magazine, 50:S11–S15, September 2005. 3. Haker , M. E. Hardware Realization of a Transform Domain Communication Sys- tem. Master’s

The evolving clinical picture of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS): A look at 1310 patients over 16 years.

PubMed

Doiron, R Christopher; Tripp, Dean A; Tolls, Victoria; Nickel, J Curtis

2018-06-01

Two decades of increasing understanding of etiopathogenesis and clinical phenotyping produces an impression the clinical face of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is changing. We sought to retrospectively analyze trends in CP/CPPS patients presenting to our clinic for evaluation over a 16-year period. Patients with CP/CPPS presenting to a tertiary clinic were evaluated prospectively from 1998-2014 with Chronic Prostatitis Symptom Index (CPSI) and UPOINT (urinary, psychosocial, organ-specific, infection, neurogenic, and tenderness) categorization. Patients were stratified in four cohorts, based on year of presentation, and we retrospectively analyzed variations in symptom scores and patterns, UPOINT categorization, and treatment modalities amongst cohorts. Mean age of the 1310 CP/CPPS patients was 44.7 years, while mean CPSI pain, urination, and total scores were 10.6, 4.8, and 23.3, respectively. The most prevalent UPOINT domain, urinary (U) (71.8%) was associated with a higher CPSI urination score (6.3), more frequent penile tip pain (37%), dysuria (48%), and more treatment with alpha-blockers (70%). Increase in UPOINT domains was associated with higher CPSI pain, quality of life (QoL), and total scores. Trends over time included increased prevalence of psychosocial (P), organ (O), and tenderness (T) domains, as well as increased use of alpha-blockers, neuromodulation, and phytotherapy as treatment modalities. There was little variation in age, CPSI scores, and pain locations over time. The changing clinical face of CP/CPPS reflects the increased recognition of psychosocial (P domain) and pelvic floor pain (T domain), along with the concomitant use of associated therapies. There was little variation of pain/urinary symptom patterns and QoL.

Ft. Drum, New York. Limited Surface Observations Climatic Summary (LISOCS). Parts A-F.

DTIC Science & Technology

1987-09-01

putO r. , j FEDERAL BUILDING DI 5 trf - ,:;, lIril t 1 ,d."ASHEVILLE, N.C. 28801- 2723 04 88 88 1 29 008 REVIEW AND APPROVAL STATEMENT USAFETAC/DS-87...IlTitle: (LISOCS) Ft Drum NY. 12Personal Autor(s): 1 3aType of Reprt: Da ti Summa ry l3bTime Covered: May 44-Aug 46, May 70-Aug; 74 , Sep 48-Apr 87...l4Date of Reprt. Sep 87 l5t~p__Count: 312 17C0SATI Codes: Field-04, Group-02 l8Subjet Terms: *cl~mtoog~y *weat’ 1 .r -)rerj~t’loinditions winds prec

Studies of Coherent Synchrotron Radiation with the Discontinuous Galerkin Method

NASA Astrophysics Data System (ADS)

Bizzozero, David A.

In this thesis, we present methods for integrating Maxwell's equations in Frenet-Serret coordinates in several settings using discontinuous Galerkin (DG) finite element method codes in 1D, 2D, and 3D. We apply these routines to the study of coherent synchrotron radiation, an important topic in accelerator physics. We build upon the published computational work of T. Agoh and D. Zhou in solving Maxwell's equations in the frequency-domain using a paraxial approximation which reduces Maxwell's equations to a Schrodinger-like system. We also evolve Maxwell's equations in the time-domain using a Fourier series decomposition with 2D DG motivated by an experiment performed at the Canadian Light Source. A comparison between theory and experiment has been published (Phys. Rev. Lett. 114, 204801 (2015)). Lastly, we devise a novel approach to integrating Maxwell's equations with 3D DG using a Galilean transformation and demonstrate proof-of-concept. In the above studies, we examine the accuracy, efficiency, and convergence of DG.

RNA Binding of T-cell Intracellular Antigen-1 (TIA-1) C-terminal RNA Recognition Motif Is Modified by pH Conditions*

PubMed Central

Cruz-Gallardo, Isabel; Aroca, Ángeles; Persson, Cecilia; Karlsson, B. Göran; Díaz-Moreno, Irene

2013-01-01

T-cell intracellular antigen-1 (TIA-1) is a DNA/RNA-binding protein that regulates critical events in cell physiology by the regulation of pre-mRNA splicing and mRNA translation. TIA-1 is composed of three RNA recognition motifs (RRMs) and a glutamine-rich domain and binds to uridine-rich RNA sequences through its C-terminal RRM2 and RRM3 domains. Here, we show that RNA binding mediated by either isolated RRM3 or the RRM23 construct is controlled by slight environmental pH changes due to the protonation/deprotonation of TIA-1 RRM3 histidine residues. The auxiliary role of the C-terminal RRM3 domain in TIA-1 RNA recognition is poorly understood, and this work provides insight into its binding mechanisms. PMID:23902765

Expression of simian virus 40 T antigen in Escherichia coli: localization of T-antigen origin DNA-binding domain to within 129 amino acids.

PubMed Central

Arthur, A K; Höss, A; Fanning, E

1988-01-01

The genomic coding sequence of the large T antigen of simian virus 40 (SV40) was cloned into an Escherichia coli expression vector by joining new restriction sites, BglII and BamHI, introduced at the intron boundaries of the gene. Full-length large T antigen, as well as deletion and amino acid substitution mutants, were inducibly expressed from the lac promoter of pUC9, albeit with different efficiencies and protein stabilities. Specific interaction with SV40 origin DNA was detected for full-length T antigen and certain mutants. Deletion mutants lacking T-antigen residues 1 to 130 and 260 to 708 retained specific origin-binding activity, demonstrating that the region between residues 131 and 259 must carry the essential binding domain for DNA-binding sites I and II. A sequence between residues 302 and 320 homologous to a metal-binding "finger" motif is therefore not required for origin-specific binding. However, substitution of serine for either of two cysteine residues in this motif caused a dramatic decrease in origin DNA-binding activity. This region, as well as other regions of the full-length protein, may thus be involved in stabilizing the DNA-binding domain and altering its preference for binding to site I or site II DNA. Images PMID:2835505

Use of biphase-coded pulses for wideband data storage in time-domain optical memories.

PubMed

Shen, X A; Kachru, R

1993-06-10

We demonstrate that temporally long laser pulses with appropriate phase modulation can replace either temporally brief or frequency-chirped pulses in a time-domain optical memory to store and retrieve information. A 1.65-µs-long write pulse was biphase modulated according to the 13-bit Barker code for storing multiple bits of optical data into a Pr(3+):YAlO(3) crystal, and the stored information was later recalled faithfully by using a read pulse that was identical to the write pulse. Our results further show that the stored data cannot be retrieved faithfully if mismatched write and read pulses are used. This finding opens up the possibility of designing encrypted optical memories for secure data storage.

Mutation Screening of 1,237 Cancer Genes across Six Model Cell Lines of Basal-Like Breast Cancer.

PubMed

Olsson, Eleonor; Winter, Christof; George, Anthony; Chen, Yilun; Törngren, Therese; Bendahl, Pär-Ola; Borg, Åke; Gruvberger-Saal, Sofia K; Saal, Lao H

2015-01-01

Basal-like breast cancer is an aggressive subtype generally characterized as poor prognosis and lacking the expression of the three most important clinical biomarkers, estrogen receptor, progesterone receptor, and HER2. Cell lines serve as useful model systems to study cancer biology in vitro and in vivo. We performed mutational profiling of six basal-like breast cancer cell lines (HCC38, HCC1143, HCC1187, HCC1395, HCC1954, and HCC1937) and their matched normal lymphocyte DNA using targeted capture and next-generation sequencing of 1,237 cancer-associated genes, including all exons, UTRs and upstream flanking regions. In total, 658 somatic variants were identified, of which 378 were non-silent (average 63 per cell line, range 37-146) and 315 were novel (not present in the Catalogue of Somatic Mutations in Cancer database; COSMIC). 125 novel mutations were confirmed by Sanger sequencing (59 exonic, 48 3'UTR and 10 5'UTR, 1 splicing), with a validation rate of 94% of high confidence variants. Of 36 mutations previously reported for these cell lines but not detected in our exome data, 36% could not be detected by Sanger sequencing. The base replacements C/G>A/T, C/G>G/C, C/G>T/A and A/T>G/C were significantly more frequent in the coding regions compared to the non-coding regions (OR 3.2, 95% CI 2.0-5.3, P<0.0001; OR 4.3, 95% CI 2.9-6.6, P<0.0001; OR 2.4, 95% CI 1.8-3.1, P<0.0001; OR 1.8, 95% CI 1.2-2.7, P = 0.024, respectively). The single nucleotide variants within the context of T[C]T/A[G]A and T[C]A/T[G]A were more frequent in the coding than in the non-coding regions (OR 3.7, 95% CI 2.2-6.1, P<0.0001; OR 3.8, 95% CI 2.0-7.2, P = 0.001, respectively). Copy number estimations were derived from the targeted regions and correlated well to Affymetrix SNP array copy number data (Pearson correlation 0.82 to 0.96 for all compared cell lines; P<0.0001). These mutation calls across 1,237 cancer-associated genes and identification of novel variants will aid in the design and interpretation of biological experiments using these six basal-like breast cancer cell lines.

The complete mitochondrial genome of Lota lota (Gadiformes: Gadidae) from the Burqin River in China.

PubMed

Lu, Zhichuang; Zhang, Nan; Song, Na; Gao, Tianxiang

2016-05-01

In this study, the complete mitochondrial genome (mitogenome) sequence of Lota lota has been determined by long polymerase chain reaction and primer walking methods. The mitogenome is a circular molecule of 16,519 bp in length and contains 37 mitochondrial genes including 13 protein-coding genes, 2 ribosomal RNA (rRNA), 22 transfer RNA (tRNA) and a control region as other bony fishes. Within the control region, we identified the termination-associated sequence domain (TAS), the central conserved sequence block domains (CSB-F and CSB-D), and the conserved sequence block domains (CSB-1, CSB-2 and CSB-3).

Expression and characterization of truncated human heme oxygenase (hHO-1) and a fusion protein of hHO-1 with human cytochrome P450 reductase.

PubMed

Wilks, A; Black, S M; Miller, W L; Ortiz de Montellano, P R

1995-04-04

A human heme oxygenase (hHO-1) gene without the sequence coding for the last 23 amino acids has been expressed in Escherichia coli behind the pho A promoter. The truncated enzyme is obtained in high yields as a soluble, catalytically-active protein, making it available for the first time for detailed mechanistic studies. The purified, truncated hHO-1/heme complex is spectroscopically indistinguishable from that of the rat enzyme and converts heme to biliverdin when reconstituted with rat liver cytochrome P450 reductase. A self-sufficient heme oxygenase system has been obtained by fusing the truncated hHO-1 gene to the gene for human cytochrome P450 reductase without the sequence coding for the 20 amino acid membrane binding domain. Expression of the fusion protein in pCWori+ yields a protein that only requires NADPH for catalytic turnover. The failure of exogenous cytochrome P450 reductase to stimulate turnover and the insensitivity of the catalytic rate toward changes in ionic strength establish that electrons are transferred intramolecularly between the reductase and heme oxygenase domains of the fusion protein. The Vmax for the fusion protein is 2.5 times higher than that for the reconstituted system. Therefore, either the covalent tether does not interfere with normal docking and electron transfer between the flavin and heme domains or alternative but equally efficient electron transfer pathways are available that do not require specific docking.

A DAFT DL_POLY distributed memory adaptation of the Smoothed Particle Mesh Ewald method

NASA Astrophysics Data System (ADS)

Bush, I. J.; Todorov, I. T.; Smith, W.

2006-09-01

The Smoothed Particle Mesh Ewald method [U. Essmann, L. Perera, M.L. Berkowtz, T. Darden, H. Lee, L.G. Pedersen, J. Chem. Phys. 103 (1995) 8577] for calculating long ranged forces in molecular simulation has been adapted for the parallel molecular dynamics code DL_POLY_3 [I.T. Todorov, W. Smith, Philos. Trans. Roy. Soc. London 362 (2004) 1835], making use of a novel 3D Fast Fourier Transform (DAFT) [I.J. Bush, The Daresbury Advanced Fourier transform, Daresbury Laboratory, 1999] that perfectly matches the Domain Decomposition (DD) parallelisation strategy [W. Smith, Comput. Phys. Comm. 62 (1991) 229; M.R.S. Pinches, D. Tildesley, W. Smith, Mol. Sim. 6 (1991) 51; D. Rapaport, Comput. Phys. Comm. 62 (1991) 217] of the DL_POLY_3 code. In this article we describe software adaptations undertaken to import this functionality and provide a review of its performance.

IRS-1 activates phosphatidylinositol 3'-kinase by associating with src homology 2 domains of p85.

PubMed Central

Myers, M G; Backer, J M; Sun, X J; Shoelson, S; Hu, P; Schlessinger, J; Yoakim, M; Schaffhausen, B; White, M F

1992-01-01

IRS-1 is an insulin receptor substrate that undergoes tyrosine phosphorylation and associates with the phosphatidylinositol (PtdIns) 3'-kinase immediately after insulin stimulation. Recombinant IRS-1 protein was tyrosine phosphorylated by the insulin receptor in vitro and associated with the PtdIns 3'-kinase from lysates of quiescent 3T3 fibroblasts. Bacterial fusion proteins containing the src homology 2 domains (SH2 domains) of the 85-kDa subunit (p85) of the PtdIns 3'-kinase bound quantitatively to tyrosine phosphorylated, but not unphosphorylated, IRS-1, and this association was blocked by phosphotyrosine-containing synthetic peptides. Moreover, the phosphorylated peptides and the SH2 domains each inhibited binding of PtdIns 3'-kinase to IRS-1. Phosphorylated IRS-1 activated PtdIns 3'-kinase in anti-p85 immunoprecipitates in vitro, and this activation was blocked by SH2 domain fusion proteins. These data suggest that the interaction between PtdIns 3'-kinase and IRS-1 is mediated by tyrosine phosphorylated motifs on IRS-1 and the SH2 domains of p85, and IRS-1 activates PtdIns 3'-kinase by binding to the SH2 domains of p85. Thus, IRS-1 likely serves to transmit the insulin signal by binding and regulating intracellular enzymes containing SH2 domains. Images PMID:1332046

A polymorphism in a transporter of testosterone is a determinant of androgen independence in prostate cancer.

PubMed

Sharifi, Nima; Hamada, Akinobu; Sissung, Tristan; Danesi, Romano; Venzon, David; Baum, Caitlin; Gulley, James L; Price, Douglas K; Dahut, William L; Figg, William D

2008-08-05

To determine if patients with advanced prostate cancer carrying a polymorphism that codes for a more active testosterone transporter have less durable responses to androgen-deprivation therapy (ADT) than patients not carrying this polymorphism. We previously determined that a polymorphism in SLCO1B3 affects testosterone transport and that those men who have at least one wild-type T allele at the 334 T > G polymorphism in this gene have a shorter survival. We hypothesized that the T allele which increases testosterone transport would be associated with a shorter interval from ADT to androgen independence. We examined the association between this SLCO1B3 polymorphism and time from ADT to androgen independence, ADT to prostate-specific antigen (PSA) nadir and PSA nadir to androgen independence in 68 Caucasian patients with advanced prostate cancer who were treated with ADT with metastatic disease (D2) or biochemical failure with no metastatic disease (D0). When examined separately, patients in the individual stages tended to have a shorter time to androgen independence with the T allele in the D0 (P = 0.11) and D2 (P = 0.18) groups. Combining these groups and stratifying by stage yielded a statistically significant shorter time to androgen independence with the T allele (P = 0.048). A polymorphism in a transporter that increases testosterone import is associated with a shorter time to androgen independence in patients with prostate cancer who are treated with ADT.

User's manual for three dimensional FDTD version A code for scattering from frequency-independent dielectric materials

NASA Technical Reports Server (NTRS)

Beggs, John H.; Luebbers, Raymond J.; Kunz, Karl S.

1991-01-01

The Finite Difference Time Domain Electromagnetic Scattering Code Version A is a three dimensional numerical electromagnetic scattering code based upon the Finite Difference Time Domain Technique (FDTD). This manual provides a description of the code and corresponding results for the default scattering problem. In addition to the description, the operation, resource requirements, version A code capabilities, a description of each subroutine, a brief discussion of the radar cross section computations, and a discussion of the scattering results.

Activation of phosphatidylinositol-3 kinase by nerve growth factor involves indirect coupling of the trk proto-oncogene with src homology 2 domains.

PubMed

Ohmichi, M; Decker, S J; Saltiel, A R

1992-10-01

Growth factor receptor tyrosine kinases can form stable associations with intracellular proteins that contain src homology (SH) 2 domains, including the p85 regulatory subunit of phosphatidylinositol (PI)-3 kinase. The activation of this enzyme by growth factors is evaluated in PC12 pheochromocytoma cells and NIH 3T3 fibroblasts expressing the pp140c-trk nerve growth factor (NGF) receptor (3T3-c-trk). NGF causes the rapid stimulation of PI-3 kinase activity detected in anti-phosphotyrosine, but not in anti-trk, immunoprecipitates. This effect coincides with the tyrosine phosphorylation of two proteins, with molecular masses of of 100 kd and 110 kd, that coimmunoprecipitate with p85. Similar phosphorylation patterns are induced when an immobilized fusion protein containing the amino-terminal SH2 domain of p85 is used to precipitate tyrosine-phosphorylated proteins. Thus, although NGF produces the rapid activation of PI-3 kinase through a mechanism that involves tyrosine phosphorylation, there is no evidence for tyrosine phosphorylation of p85, or for its ligand-dependent association with the NGF receptor. Perhaps another phosphoprotein may link the NGF receptor to this enzyme.

Phase-separation mechanism for C-terminal hyperphosphorylation of RNA polymerase II.

PubMed

Lu, Huasong; Yu, Dan; Hansen, Anders S; Ganguly, Sourav; Liu, Rongdiao; Heckert, Alec; Darzacq, Xavier; Zhou, Qiang

2018-06-01

Hyperphosphorylation of the C-terminal domain (CTD) of the RPB1 subunit of human RNA polymerase (Pol) II is essential for transcriptional elongation and mRNA processing 1-3 . The CTD contains 52 heptapeptide repeats of the consensus sequence YSPTSPS. The highly repetitive nature and abundant possible phosphorylation sites of the CTD exert special constraints on the kinases that catalyse its hyperphosphorylation. Positive transcription elongation factor b (P-TEFb)-which consists of CDK9 and cyclin T1-is known to hyperphosphorylate the CTD and negative elongation factors to stimulate Pol II elongation 1,4,5 . The sequence determinant on P-TEFb that facilitates this action is currently unknown. Here we identify a histidine-rich domain in cyclin T1 that promotes the hyperphosphorylation of the CTD and stimulation of transcription by CDK9. The histidine-rich domain markedly enhances the binding of P-TEFb to the CTD and functional engagement with target genes in cells. In addition to cyclin T1, at least one other kinase-DYRK1A 6 -also uses a histidine-rich domain to target and hyperphosphorylate the CTD. As a low-complexity domain, the histidine-rich domain also promotes the formation of phase-separated liquid droplets in vitro, and the localization of P-TEFb to nuclear speckles that display dynamic liquid properties and are sensitive to the disruption of weak hydrophobic interactions. The CTD-which in isolation does not phase separate, despite being a low-complexity domain-is trapped within the cyclin T1 droplets, and this process is enhanced upon pre-phosphorylation by CDK7 of transcription initiation factor TFIIH 1-3 . By using multivalent interactions to create a phase-separated functional compartment, the histidine-rich domain in kinases targets the CTD into this environment to ensure hyperphosphorylation and efficient elongation of Pol II.

A Concept for Run-Time Support of the Chapel Language

NASA Technical Reports Server (NTRS)

James, Mark

2006-01-01

A document presents a concept for run-time implementation of other concepts embodied in the Chapel programming language. (Now undergoing development, Chapel is intended to become a standard language for parallel computing that would surpass older such languages in both computational performance in the efficiency with which pre-existing code can be reused and new code written.) The aforementioned other concepts are those of distributions, domains, allocations, and access, as defined in a separate document called "A Semantic Framework for Domains and Distributions in Chapel" and linked to a language specification defined in another separate document called "Chapel Specification 0.3." The concept presented in the instant report is recognition that a data domain that was invented for Chapel offers a novel approach to distributing and processing data in a massively parallel environment. The concept is offered as a starting point for development of working descriptions of functions and data structures that would be necessary to implement interfaces to a compiler for transforming the aforementioned other concepts from their representations in Chapel source code to their run-time implementations.

TEAMBLOCKS: HYBRID ABSTRACTIONS FOR PROVABLE MULTI-AGENT AUTONOMY

DTIC Science & Technology

2017-07-28

Raspberry Pi 23 can easily satisfy control loop periods on the order of 10−3s. Thus, we assume that the time to execute a piece of control code, ∆t...Release; Distribution Unlimited. 23 State Space The state space of the aircraft is X = R3 × SO(3) × R3 × R3; states consist of • pI ∈ R3, the...the tbdemo_ghaexecution script uses this operation to make feedback system out of the product of the linear system and PI controller. tbread

Domain Adaptation with Conditional Transferable Components

PubMed Central

Gong, Mingming; Zhang, Kun; Liu, Tongliang; Tao, Dacheng; Glymour, Clark; Schölkopf, Bernhard

2017-01-01

Domain adaptation arises in supervised learning when the training (source domain) and test (target domain) data have different distributions. Let X and Y denote the features and target, respectively, previous work on domain adaptation mainly considers the covariate shift situation where the distribution of the features P(X) changes across domains while the conditional distribution P(Y∣X) stays the same. To reduce domain discrepancy, recent methods try to find invariant components T(X) that have similar P(T(X)) on different domains by explicitly minimizing a distribution discrepancy measure. However, it is not clear if P(Y∣T(X)) in different domains is also similar when P(Y∣X) changes. Furthermore, transferable components do not necessarily have to be invariant. If the change in some components is identifiable, we can make use of such components for prediction in the target domain. In this paper, we focus on the case where P(X∣Y) and P(Y) both change in a causal system in which Y is the cause for X. Under appropriate assumptions, we aim to extract conditional transferable components whose conditional distribution P(T(X)∣Y) is invariant after proper location-scale (LS) transformations, and identify how P(Y) changes between domains simultaneously. We provide theoretical analysis and empirical evaluation on both synthetic and real-world data to show the effectiveness of our method. PMID:28239433

708 Common and 2010 rare DISC1 locus variants identified in 1542 subjects: analysis for association with psychiatric disorder and cognitive traits.

PubMed

Thomson, P A; Parla, J S; McRae, A F; Kramer, M; Ramakrishnan, K; Yao, J; Soares, D C; McCarthy, S; Morris, S W; Cardone, L; Cass, S; Ghiban, E; Hennah, W; Evans, K L; Rebolini, D; Millar, J K; Harris, S E; Starr, J M; MacIntyre, D J; McIntosh, A M; Watson, J D; Deary, I J; Visscher, P M; Blackwood, D H; McCombie, W R; Porteous, D J

2014-06-01

A balanced t(1;11) translocation that transects the Disrupted in schizophrenia 1 (DISC1) gene shows genome-wide significant linkage for schizophrenia and recurrent major depressive disorder (rMDD) in a single large Scottish family, but genome-wide and exome sequencing-based association studies have not supported a role for DISC1 in psychiatric illness. To explore DISC1 in more detail, we sequenced 528 kb of the DISC1 locus in 653 cases and 889 controls. We report 2718 validated single-nucleotide polymorphisms (SNPs) of which 2010 have a minor allele frequency of <1%. Only 38% of these variants are reported in the 1000 Genomes Project European subset. This suggests that many DISC1 SNPs remain undiscovered and are essentially private. Rare coding variants identified exclusively in patients were found in likely functional protein domains. Significant region-wide association was observed between rs16856199 and rMDD (P=0.026, unadjusted P=6.3 × 10(-5), OR=3.48). This was not replicated in additional recurrent major depression samples (replication P=0.11). Combined analysis of both the original and replication set supported the original association (P=0.0058, OR=1.46). Evidence for segregation of this variant with disease in families was limited to those of rMDD individuals referred from primary care. Burden analysis for coding and non-coding variants gave nominal associations with diagnosis and measures of mood and cognition. Together, these observations are likely to generalise to other candidate genes for major mental illness and may thus provide guidelines for the design of future studies.

Anchoring antibodies to membranes using a diphtheria toxin T domain-ZZ fusion protein as a pH sensitive membrane anchor.

PubMed

Nizard, P; Liger, D; Gaillard, C; Gillet, D

1998-08-14

We have constructed a fusion protein, T-ZZ, in which the IgG-Fc binding protein ZZ was fused to the C-terminus of the diphtheria toxin transmembrane domain (T domain). While soluble at neutral pH, T-ZZ retained the capacity of the T domain to bind to phospholipid membranes at acidic pH. Once anchored to the membrane, the ZZ part of the protein was capable of binding mouse monoclonal or rabbit polyclonal IgG. Our results show that the T-ZZ protein can function as a pH sensitive membrane anchor for the linkage of IgG to the membrane of lipid vesicles, adherent and non-adherent cells.

Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility

PubMed Central

Wessel, Jennifer; Chu, Audrey Y; Willems, Sara M; Wang, Shuai; Yaghootkar, Hanieh; Brody, Jennifer A; Dauriz, Marco; Hivert, Marie-France; Raghavan, Sridharan; Lipovich, Leonard; Hidalgo, Bertha; Fox, Keolu; Huffman, Jennifer E; An, Ping; Lu, Yingchang; Rasmussen-Torvik, Laura J; Grarup, Niels; Ehm, Margaret G; Li, Li; Baldridge, Abigail S; Stančáková, Alena; Abrol, Ravinder; Besse, Céline; Boland, Anne; Bork-Jensen, Jette; Fornage, Myriam; Freitag, Daniel F; Garcia, Melissa E; Guo, Xiuqing; Hara, Kazuo; Isaacs, Aaron; Jakobsdottir, Johanna; Lange, Leslie A; Layton, Jill C; Li, Man; Hua Zhao, Jing; Meidtner, Karina; Morrison, Alanna C; Nalls, Mike A; Peters, Marjolein J; Sabater-Lleal, Maria; Schurmann, Claudia; Silveira, Angela; Smith, Albert V; Southam, Lorraine; Stoiber, Marcus H; Strawbridge, Rona J; Taylor, Kent D; Varga, Tibor V; Allin, Kristine H; Amin, Najaf; Aponte, Jennifer L; Aung, Tin; Barbieri, Caterina; Bihlmeyer, Nathan A; Boehnke, Michael; Bombieri, Cristina; Bowden, Donald W; Burns, Sean M; Chen, Yuning; Chen, Yii-DerI; Cheng, Ching-Yu; Correa, Adolfo; Czajkowski, Jacek; Dehghan, Abbas; Ehret, Georg B; Eiriksdottir, Gudny; Escher, Stefan A; Farmaki, Aliki-Eleni; Frånberg, Mattias; Gambaro, Giovanni; Giulianini, Franco; Goddard, William A; Goel, Anuj; Gottesman, Omri; Grove, Megan L; Gustafsson, Stefan; Hai, Yang; Hallmans, Göran; Heo, Jiyoung; Hoffmann, Per; Ikram, Mohammad K; Jensen, Richard A; Jørgensen, Marit E; Jørgensen, Torben; Karaleftheri, Maria; Khor, Chiea C; Kirkpatrick, Andrea; Kraja, Aldi T; Kuusisto, Johanna; Lange, Ethan M; Lee, I T; Lee, Wen-Jane; Leong, Aaron; Liao, Jiemin; Liu, Chunyu; Liu, Yongmei; Lindgren, Cecilia M; Linneberg, Allan; Malerba, Giovanni; Mamakou, Vasiliki; Marouli, Eirini; Maruthur, Nisa M; Matchan, Angela; McKean-Cowdin, Roberta; McLeod, Olga; Metcalf, Ginger A; Mohlke, Karen L; Muzny, Donna M; Ntalla, Ioanna; Palmer, Nicholette D; Pasko, Dorota; Peter, Andreas; Rayner, Nigel W; Renström, Frida; Rice, Ken; Sala, Cinzia F; Sennblad, Bengt; Serafetinidis, Ioannis; Smith, Jennifer A; Soranzo, Nicole; Speliotes, Elizabeth K; Stahl, Eli A; Stirrups, Kathleen; Tentolouris, Nikos; Thanopoulou, Anastasia; Torres, Mina; Traglia, Michela; Tsafantakis, Emmanouil; Javad, Sundas; Yanek, Lisa R; Zengini, Eleni; Becker, Diane M; Bis, Joshua C; Brown, James B; Adrienne Cupples, L; Hansen, Torben; Ingelsson, Erik; Karter, Andrew J; Lorenzo, Carlos; Mathias, Rasika A; Norris, Jill M; Peloso, Gina M; Sheu, Wayne H.-H.; Toniolo, Daniela; Vaidya, Dhananjay; Varma, Rohit; Wagenknecht, Lynne E; Boeing, Heiner; Bottinger, Erwin P; Dedoussis, George; Deloukas, Panos; Ferrannini, Ele; Franco, Oscar H; Franks, Paul W; Gibbs, Richard A; Gudnason, Vilmundur; Hamsten, Anders; Harris, Tamara B; Hattersley, Andrew T; Hayward, Caroline; Hofman, Albert; Jansson, Jan-Håkan; Langenberg, Claudia; Launer, Lenore J; Levy, Daniel; Oostra, Ben A; O'Donnell, Christopher J; O'Rahilly, Stephen; Padmanabhan, Sandosh; Pankow, James S; Polasek, Ozren; Province, Michael A; Rich, Stephen S; Ridker, Paul M; Rudan, Igor; Schulze, Matthias B; Smith, Blair H; Uitterlinden, André G; Walker, Mark; Watkins, Hugh; Wong, Tien Y; Zeggini, Eleftheria; Sharp, Stephen J; Forouhi, Nita G; Kerrison, Nicola D; Lucarelli, Debora ME; Sims, Matt; Barroso, Inês; McCarthy, Mark I; Arriola, Larraitz; Balkau, Beverley; Barricarte, Aurelio; Gonzalez, Carlos; Grioni, Sara; Kaaks, Rudolf; Key, Timothy J; Navarro, Carmen; Nilsson, Peter M; Overvad, Kim; Palli, Domenico; Panico, Salvatore; Quirós, J. Ramón; Rolandsson, Olov; Sacerdote, Carlotta; Sánchez, María–José; Slimani, Nadia; Tjonneland, Anne; Tumino, Rosario; van der A, Daphne L; van der Schouw, Yvonne T; Riboli, Elio; Laakso, Markku; Borecki, Ingrid B; Chasman, Daniel I; Pedersen, Oluf; Psaty, Bruce M; Shyong Tai, E; van Duijn, Cornelia M; Wareham, Nicholas J; Waterworth, Dawn M; Boerwinkle, Eric; Linda Kao, W H; Florez, Jose C; Loos, Ruth J.F.; Wilson, James G; Frayling, Timothy M; Siscovick, David S; Dupuis, Josée; Rotter, Jerome I; Meigs, James B; Scott, Robert A; Goodarzi, Mark O

2015-01-01

Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF=1.4%) with lower FG (β=−0.09±0.01 mmol l−1, P=3.4 × 10−12), T2D risk (OR[95%CI]=0.86[0.76–0.96], P=0.010), early insulin secretion (β=−0.07±0.035 pmolinsulin mmolglucose−1, P=0.048), but higher 2-h glucose (β=0.16±0.05 mmol l−1, P=4.3 × 10−4). We identify a gene-based association with FG at G6PC2 (pSKAT=6.8 × 10−6) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF=20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (β=0.02±0.004 mmol l−1, P=1.3 × 10−8). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility. PMID:25631608

An insight into the sialome of the horse fly, Tabanus bromius

PubMed Central

Ribeiro, José M.C.; Kazimirova, Maria; Takac, Peter; Andersen, John F.; Francischetti, Ivo M.B.

2015-01-01

Blood feeding animals face their host's defenses against tissue injury and blood loss while attempting to feed. One adaptation to surmount these barriers involves the evolution of a salivary potion that disarms their host's inflammatory and anti-hemostatic processes. The composition of the peptide moiety of this potion, or sialome (from the Greek sialo=saliva), can be deducted in part by proper interpretation of the blood feeder' sialotranscriptome. In this work we disclose the sialome of the blood feeding adult female Tabanus bromius. Following assembly of over 75 million Illumina reads (101 nt long) 16,683 contigs were obtained from which 4,078 coding sequences were extracted. From these, 320 were assigned as coding for putative secreted proteins. These 320 contigs mapped 85% of the reads. The antigen-5 proteins family was studied in detail, indicating three Tabanus specific clades with and without disintegrin domains, as well as with and without leukotriene binding domains. Defensins were also detailed; a clade of salivary tabanid peptides was found lacking the propeptide domain ending in the KR dipeptide signaling furin cleavage. Novel protein families were also disclosed. Viral transcripts were identified closely matching the Kotonkan virus capsid proteins. Full length Mariner transposases were also identified. A total of 3,043 coding sequences and their protein products were deposited in Genbank. Hyperlinked excel spreadsheets containing the coding sequences and their annotation are available at http://exon.niaid.nih.gov/transcriptome/T_bromius/Tbromius-web.xlsx (hyperlinked excel spreadsheet, 11 MB) and http://exon.niaid.nih.gov/transcriptome/T_bromius/Tbromius-SA.zip (Standalone excel with all local links, 360 MB). These sequences provide for a platform from which further proteomic studies may be designed to identify salivary proteins from T. bromius that are of pharmacological interest or used as immunological markers of host exposure. PMID:26369729

Comparison study of the pT distributions of the charged particles in p-Pb interactions at LHC energies

NASA Astrophysics Data System (ADS)

Ali, Y.; Tabassam, U.; Suleymanov, M.; Bhatti, A. S.

2017-10-01

Transverse momentum (pT) distributions of primary charged particles were compared to simulations using the Ultra Relativistic Quantum Molecular Dynamics (UrQMD) transport model and the HIJING 1.0 model in minimum bias p-Pb collisions at sNN = 5.02TeV in the pseudorapidity (η) regions: η < 0.3, 0.3 < η < 0.8 and 0.8 < η < 1.3 and in the transverse momentum range 0.5 < pT < 20GeV/c. The simulated distributions were then compared with the ALICE data and it was observed that UrQMD predicts systematically higher yields than HIJING 1.0. Both codes cannot describe the experimental data in the range of 0.5 < pT < 20GeV/c, though in the region of pT > 5GeV/c the model predictions are very close to the experimental results for particles with |η| < 0.3, 0.3 < η < 0.8. The ratio of the yield at forward pseudorapidity to that at |η| < 0.3 was also studied. It was observed that the predictions of the models depend on η. In the experiment there is no essential difference of yields for particles from the intervals of |η| < 0.3, 0.3 < η < 0.8 and 0.8 < η < 1.3. The differences are significant for the models where the ratios are systematically less than 1. This means that the results are not connected to a medium effect but reflect the Cronin effect. We are led to conclude that the codes cannot take into account satisfactorily the leading effect due to the asymmetric p-Pb fragmentation.

Arc1p is required for cytoplasmic confinement of synthetases and tRNA.

PubMed

Golinelli-Cohen, Marie-Pierre; Mirande, Marc

2007-06-01

In yeast, Arc1p interacts with ScMetRS and ScGluRS and operates as a tRNA-Interacting Factor (tIF) in trans of these two synthetases. Its N-terminal domain (N-Arc1p) binds the two synthetases and its C-terminal domain is an EMAPII-like domain organized around an OB-fold-based tIF. ARC1 is not an essential gene but its deletion (arc1- cells) is accompanied by a growth retardation phenotype. Here, we show that expression of N-Arc1p or of C-Arc1p alone palliates the growth defect of arc1- cells, and that bacterial Trbp111 or human p43, two proteins containing EMAPII-like domains, also improve the growth of an arc1- strain. The synthetic lethality of an arc1-los1- strain can be complemented with either ARC1 or LOS1. Expression of N-Arc1p or C-Arc1p alone does not complement an arc1-los1- phenotype, but coexpression of the two domains does. Our data demonstrate that Trbp111 or p43 may replace C-Arc1p to complement an arc1-los1- strain. The two functional domains of Arc1p (N-Arc1p and C-Arc1p) are required to get rid of the synthetic lethal phenotype but do not need to be physically linked. To get some clues to the discrete functions of N-Arc1p and C-Arc1p, we targeted ScMetRS or tIF domains to the nuclear compartment and analyzed their cellular localization by using GFP fusions, and their ability to sustain growth. Our results are consistent with a model according to which Arc1p is a bifunctional protein involved in the subcellular localization of ScMetRS and ScGluRS via its N-terminal domain and of tRNA via its C-terminal domain.

p56Lck and p59Fyn Regulate CD28 Binding to Phosphatidylinositol 3-Kinase, Growth Factor Receptor-Bound Protein GRB-2, and T Cell-Specific Protein-Tyrosine Kinase ITK: Implications for T-Cell Costimulation

NASA Astrophysics Data System (ADS)

Raab, Monika; Cai, Yun-Cai; Bunnell, Stephen C.; Heyeck, Stephanie D.; Berg, Leslie J.; Rudd, Christopher E.

1995-09-01

T-cell activation requires cooperative signals generated by the T-cell antigen receptor ξ-chain complex (TCRξ-CD3) and the costimulatory antigen CD28. CD28 interacts with three intracellular proteins-phosphatidylinositol 3-kinase (PI 3-kinase), T cell-specific protein-tyrosine kinase ITK (formerly TSK or EMT), and the complex between growth factor receptor-bound protein 2 and son of sevenless guanine nucleotide exchange protein (GRB-2-SOS). PI 3-kinase and GRB-2 bind to the CD28 phosphotyrosine-based Tyr-Met-Asn-Met motif by means of intrinsic Src-homology 2 (SH2) domains. The requirement for tyrosine phosphorylation of the Tyr-Met-Asn-Met motif for SH2 domain binding implicates an intervening protein-tyrosine kinase in the recruitment of PI 3-kinase and GRB-2 by CD28. Candidate kinases include p56Lck, p59Fyn, ξ-chain-associated 70-kDa protein (ZAP-70), and ITK. In this study, we demonstrate in coexpression studies that p56Lck and p59Fyn phosphorylate CD28 primarily at Tyr-191 of the Tyr-Met-Asn-Met motif, inducing a 3- to 8-fold increase in p85 (subunit of PI 3-kinase) and GRB-2 SH2 binding to CD28. Phosphatase digestion of CD28 eliminated binding. In contrast to Src kinases, ZAP-70 and ITK failed to induce these events. Further, ITK binding to CD28 was dependent on the presence of p56Lck and is thus likely to act downstream of p56Lck/p59Fyn in a signaling cascade. p56Lck is therefore likely to be a central switch in T-cell activation, with the dual function of regulating CD28-mediated costimulation as well as TCR-CD3-CD4 signaling.

k-t SENSE-accelerated Myocardial Perfusion MR Imaging at 3.0 Tesla - comparison with 1.5 Tesla

PubMed Central

Plein, Sven; Schwitter, Juerg; Suerder, Daniel; Greenwood, John P.; Boesiger, Peter; Kozerke, Sebastian

2008-01-01

Purpose To determine the feasibility and diagnostic accuracy of high spatial resolution myocardial perfusion MR at 3.0 Tesla using k-space and time domain undersampling with sensitivity encoding (k-t SENSE). Materials and Methods The study was reviewed and approved by the local ethic review board. k-t SENSE perfusion MR was performed at 1.5 Tesla and 3.0 Tesla (saturation recovery gradient echo pulse sequence, repetition time/echo time 3.0ms/1.0ms, flip angle 15°, 5x k-t SENSE acceleration, spatial resolution 1.3×1.3×10mm3). Fourteen volunteers were studied at rest and 37 patients during adenosine stress. In volunteers, comparison was also made with standard-resolution (2.5×2.5×10mm3) 2x SENSE perfusion MR at 3.0 Tesla. Image quality, artifact scores, signal-to-noise ratios (SNR) and contrast-enhancement ratios (CER) were derived. In patients, diagnostic accuracy of visual analysis to detect >50% diameter stenosis on quantitative coronary angiography was determined by receiver-operator-characteristics (ROC). Results In volunteers, image quality and artifact scores were similar for 3.0 Tesla and 1.5 Tesla, while SNR was higher (11.6 vs. 5.6) and CER lower (1.1 vs. 1.5, p=0.012) at 3.0 Tesla. Compared with standard-resolution perfusion MR, image quality was higher for k-t SENSE (3.6 vs. 3.1, p=0.04), endocardial dark rim artifacts were reduced (artifact thickness 1.6mm vs. 2.4mm, p<0.001) and CER similar. In patients, area under the ROC curve for detection of coronary stenosis was 0.89 and 0.80, p=0.21 for 3.0 Tesla and 1.5 Tesla, respectively. Conclusions k-t SENSE accelerated high-resolution perfusion MR at 3.0 Tesla is feasible with similar artifacts and diagnostic accuracy as at 1.5 Tesla. Compared with standard-resolution perfusion MR, image quality is improved and artifacts are reduced. PMID:18936311

KSOS Secure Unix Verification Plan (Kernelized Secure Operating System).

DTIC Science & Technology

1980-12-01

shall be handled as proprietary information untii 5 Apri 1978. After that time, the Government m-. distribute the document as it sees fit. UNIX and PWB...Accession For P-’(’ T.’i3 :- NTI G.;:’... &I : " \\ " Y: Codes mdlc/or 71!O lii WDL-TR7809 KSOS VERIFICATION PLAN SECTION I INTRODUCTION "’The purpose...funding, additional tools may be available by the time they are needed for FSOS verification. We intend to use the best available technology in

Mechanisms of splicing-dependent trans-synaptic adhesion by PTPδ-IL1RAPL1/IL-1RAcP for synaptic differentiation

NASA Astrophysics Data System (ADS)

Yamagata, Atsushi; Yoshida, Tomoyuki; Sato, Yusuke; Goto-Ito, Sakurako; Uemura, Takeshi; Maeda, Asami; Shiroshima, Tomoko; Iwasawa-Okamoto, Shiho; Mori, Hisashi; Mishina, Masayoshi; Fukai, Shuya

2015-04-01

Synapse formation is triggered through trans-synaptic interaction between pairs of pre- and postsynaptic adhesion molecules, the specificity of which depends on splice inserts known as `splice-insert signaling codes'. Receptor protein tyrosine phosphatase δ (PTPδ) can bidirectionally induce pre- and postsynaptic differentiation of neurons by trans-synaptically binding to interleukin-1 receptor accessory protein (IL-1RAcP) and IL-1RAcP-like-1 (IL1RAPL1) in a splicing-dependent manner. Here, we report crystal structures of PTPδ in complex with IL1RAPL1 and IL-1RAcP. The first immunoglobulin-like (Ig) domain of IL1RAPL1 directly recognizes the first splice insert, which is critical for binding to IL1RAPL1. The second splice insert functions as an adjustable linker that positions the Ig2 and Ig3 domains of PTPδ for simultaneously interacting with the Ig1 domain of IL1RAPL1 or IL-1RAcP. We further identified the IL1RAPL1-specific interaction, which appears coupled to the first-splice-insert-mediated interaction. Our results thus reveal the decoding mechanism of splice-insert signaling codes for synaptic differentiation induced by trans-synaptic adhesion between PTPδ and IL1RAPL1/IL-1RAcP.

Co-simulation coupling spectral/finite elements for 3D soil/structure interaction problems

NASA Astrophysics Data System (ADS)

Zuchowski, Loïc; Brun, Michael; De Martin, Florent

2018-05-01

The coupling between an implicit finite elements (FE) code and an explicit spectral elements (SE) code has been explored for solving the elastic wave propagation in the case of soil/structure interaction problem. The coupling approach is based on domain decomposition methods in transient dynamics. The spatial coupling at the interface is managed by a standard coupling mortar approach, whereas the time integration is dealt with an hybrid asynchronous time integrator. An external coupling software, handling the interface problem, has been set up in order to couple the FE software Code_Aster with the SE software EFISPEC3D.

High resolution crystal structure of the Grb2 SH2 domain with a phosphopeptide derived from CD28.

PubMed

Higo, Kunitake; Ikura, Teikichi; Oda, Masayuki; Morii, Hisayuki; Takahashi, Jun; Abe, Ryo; Ito, Nobutoshi

2013-01-01

Src homology 2 (SH2) domains play a critical role in cellular signal transduction. They bind to peptides containing phosphotyrosine (pY) with various specificities that depend on the flanking amino-acid residues. The SH2 domain of growth-factor receptor-bound protein 2 (Grb2) specifically recognizes pY-X-N-X, whereas the SH2 domains in phosphatidylinositol 3-kinase (PI3K) recognize pY-X-X-M. Binding of the pY site in CD28 (pY-M-N-M) by PI3K and Grb2 through their SH2 domains is a key step that triggers the CD28 signal transduction for T cell activation and differentiation. In this study, we determined the crystal structure of the Grb2 SH2 domain in complex with a pY-containing peptide derived from CD28 at 1.35 Å resolution. The peptide was found to adopt a twisted U-type conformation, similar to, but distinct from type-I β-turn. In all previously reported crystal structures, the peptide bound to the Grb2 SH2 domains adopts a type-I β-turn conformation, except those with a proline residue at the pY+3 position. Molecular modeling also suggests that the same peptide bound to PI3K might adopt a very different conformation.

Domain organization of p130, PLC-related catalytically inactive protein, and structural basis for the lack of enzyme activity.

PubMed

Kanematsu, T; Yoshimura, K; Hidaka, K; Takeuchi, H; Katan, M; Hirata, M

2000-05-01

The 130-kDa protein (p130) was isolated as a novel inositol 1,4, 5-trisphosphate [Ins(1,4,5)P3]-binding protein similar to phospholipase C-delta1 (PLC-delta1), but lacking catalytic activity [Kanematsu, T., Takeya, H., Watanabe, Y., Ozaki, S., Yoshida, M., Koga, T., Iwanaga, S. & Hirata, M. (1992) J. Biol. Chem. 267, 6518-6525; Kanematsu, T., Misumi, Y., Watanabe, Y., Ozaki, S., Koga, T., Iwanaga, S., Ikehara, Y. & Hirata, M. (1996) Biochem. J. 313, 319-325]. To test experimentally the domain organization of p130 and structural basis for lack of PLC activity, we subjected p130 to limited proteolysis and also constructed a number of chimeras with PLC-delta1. Trypsin treatment of p130 produced four major polypeptides with molecular masses of 86 kDa, 55 kDa, 33 kDa and 25 kDa. Two polypeptides of 86 kDa and 55 kDa started at Lys93 and were calculated to end at Arg851 and Arg568, respectively. Using the same approach, it has been found that the polypeptides of 33 kDa and 25 kDa are likely to correspond to regions between Val569 and Arg851 and Lys869 and Leu1096, respectively. All the proteolytic sites were in interconnecting regions between the predicted domains, therefore supporting domain organization based on sequence similarity to PLC-delta1 and demonstrating that all domains of p130, including the unique region at the C-terminus, are stable, tightly folded structures. p130 truncated at either or both the N-terminus (94 amino acids) and C-terminus (851-1096 amino acids) expressed in COS-1 cells showed no catalytic activity, indicating that p130 has intrinsically no PLC activity. A number of chimeric molecules between p130 and PLC-delta1 were constructed and assayed for PLC activity. It was shown that structural differences in interdomain interactions exist between the two proteins, as only some domains of p130 could replace the corresponding structures in PLC-delta1 to form a functional enzyme. These results suggest that p130 and the related proteins could represent a new protein family that may play some distinct role in cells due to the capability of binding Ins(1,4,5)P3 but the lack of catalytic activity.

The Paraoxonase 1 Gene c.-108C>T SNP in the Promoter Is Associated with Risk for Glioma in Mexican Patients, but Not the p.L55M or p.Q192R Polymorphisms in the Coding Region.

PubMed

González-Herrera, Lizbeth; Gamas-Trujillo, Pablo Alejandro; Medina-Escobedo, Gilberto; Oaxaca-Castillo, David; Pérez-Mendoza, Gerardo; Williams-Jacquez, Dayana; Canto-Cetina, Thelma; Vargas-García, Rubén Darío

2015-09-01

To evaluate the association of the paraoxonase 1 (PON1) gene polymorphisms c.-108C>T, p.L55M, and p.Q192R with the risk of glioma in Southeast Mexico. Decreased PON1 activity caused by polymorphisms has been observed in gliomas, thus supporting the theory that PON1 is involved in tumorigenesis in the brain. Sixty-seven glioma patients and 58 control individuals were included. Three PON1 polymorphisms were genotyped by real-time PCR allelic discrimination using TaqMan probes: c.-108C>T in the promoter region, p.Q192R and p.L55M, both of which were in the coding region. Allele, genotype, and haplotype frequencies were assessed in cases and controls to test for statistical associations (STATA 10.2 package). Significant differences were found for the PON1 c.-108C>T polymorphism between the cases and controls. Compared to the controls the cases were more likely to be CT heterozygous (p =  0.002) or TT homozygous (p = 0.036); similarly cases were more likely to possess a T allele (p = 0.032). In contrast, the p.L55M and p.Q192R polymorphisms did not show significant differences between the glioma cases and controls (p > 0.05). The PON1 c.-108C>T polymorphism in the promoter region is associated with genetic risk for glioma. Conversely, p.L55M and p.Q192R polymorphisms in the coding region do not seem to have an influence in this population.

Norovirus P particle efficiently elicits innate, humoral and cellular immunity.

PubMed

Fang, Hao; Tan, Ming; Xia, Ming; Wang, Leyi; Jiang, Xi

2013-01-01

Norovirus (NoV) P domain complexes, the 24 mer P particles and the P dimers, induced effective humoral immunity, but their role in the cellular immune responses remained unclear. We reported here a study on cellular immune responses of the two P domain complexes in comparison with the virus-like particle (VLP) of a GII.4 NoV (VA387) in mice. The P domain complexes induced significant central memory CD4(+) T cell phenotypes (CD4(+) CD44(+) CD62L(+) CCR7(+)) and activated polyclonal CD4(+) T cells as shown by production of Interleukin (IL)-2, Interferon (IFN)-γ, and Tumor Necrosis Factor (TNF)-α. Most importantly, VA387-specific CD4(+) T cell epitope induced a production of IFN-γ, indicating an antigen-specific CD4(+) T cell response in P domain complex-immunized mice. Furthermore, P domain complexes efficiently induced bone marrow-derived dendritic cell (BMDC) maturation, evidenced by up-regulation of co-stimulatory and MHC class II molecules, as well as production of IL-12 and IL-1β. Finally, P domain complex-induced mature dendritic cells (DCs) elicited proliferation of specific CD4(+) T cells targeting VA387 P domain. Overall, we conclude that the NoV P domain complexes are efficiently presented by DCs to elicit not only humoral but also cellular immune responses against NoVs. Since the P particle is highly effective for both humoral and cellular immune responses and easily produced in Escherichia coli (E. coli), it is a good choice of vaccine against NoVs and a vaccine platform against other diseases.

A 3D spectral anelastic hydrodynamic code for shearing, stratified flows

NASA Astrophysics Data System (ADS)

Barranco, Joseph A.; Marcus, Philip S.

2006-11-01

We have developed a three-dimensional (3D) spectral hydrodynamic code to study vortex dynamics in rotating, shearing, stratified systems (e.g., the atmosphere of gas giant planets, protoplanetary disks around newly forming protostars). The time-independent background state is stably stratified in the vertical direction and has a unidirectional linear shear flow aligned with one horizontal axis. Superposed on this background state is an unsteady, subsonic flow that is evolved with the Euler equations subject to the anelastic approximation to filter acoustic phenomena. A Fourier Fourier basis in a set of quasi-Lagrangian coordinates that advect with the background shear is used for spectral expansions in the two horizontal directions. For the vertical direction, two different sets of basis functions have been implemented: (1) Chebyshev polynomials on a truncated, finite domain, and (2) rational Chebyshev functions on an infinite domain. Use of this latter set is equivalent to transforming the infinite domain to a finite one with a cotangent mapping, and using cosine and sine expansions in the mapped coordinate. The nonlinear advection terms are time-integrated explicitly, the pressure/enthalpy terms are integrated semi-implicitly, and the Coriolis force and buoyancy terms are treated semi-analytically. We show that internal gravity waves can be damped by adding new terms to the Euler equations. The code exhibits excellent parallel performance with the message passing interface (MPI). As a demonstration of the code, we simulate the merger of two 3D vortices in the midplane of a protoplanetary disk.

SNL/JAEA Collaborations on Sodium Fire Benchmarking.

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

Clark, Andrew Jordan; Denman, Matthew R; Takata, Takashi

Two sodium spray fire experiments performed by Sandia National Laboratories (SNL) were used for a code - to - code comparison between CONTAIN - LMR and SPHINCS. Both computer codes are used for modeling sodium accidents in sodium fast reactors. The comparison between the two codes provides insights into the ability of both codes to model sodium spray fires. The SNL T3 and T4 experiments are 20 kg sodium spray fires with sodium spray temperature s of 200 deg C and 500 deg C, respe ctively. Given the relatively low sodium temperature in the SNL T3 experiment, the sodium spraymore » experienced a period of non - combustion. The vessel in the SNL T4 experiment experienced a rapid pressurization that caused of the instrumentation ports to fail during the sodium spray. Despite these unforeseen difficulties, both codes were shown in good agreement with the experiment s . The subsequent pool fire that develops from the unburned sodium spray is a significant characteristic of the T3 experiment. SPHIN CS showed better long - term agreement with the SNL T3 experiment than CONTAIN - LMR. The unexpected port failure during the SNL T4 experiment presented modelling challenges. The time at which the port failure occurred is unknown, but is believed to have occur red at about 11 seconds into the sodium spray fire. The sensitivity analysis for the SNL T4 experiment shows that with a port failure, the sodium spray fire can still maintain elevated pressures during the spray.« less

Variability of the caprine whey protein genes and their association with milk yield, composition and renneting properties in the Sarda breed. 1. The LALBA gene.

PubMed

Dettori, Maria Luisa; Pazzola, Michele; Paschino, Pietro; Pira, Maria Giovanna; Vacca, Giuseppe Massimo

2015-11-01

The 5' flanking region and 3' UTR of the caprine LALBA gene were analysed by SSCP and sequencing. A total of nine SNPs were detected: three in the promoter region, two were synonymous coding SNPs at exon-1, and four SNPs were in exon-4, within the 3'UTR. The nucleotide changes located in the promoter region (c.-358T>C, c.-163G>A, c.-121T>G) were genotyped by SSCP in 263 Sarda goats to evaluate their possible effect on milk yield, composition and renneting properties. We observed an effect of the three SNPs on milk yield and lactose content. Genotypes TT and CT at c.-358T>C (P A (P C and c.-121T>G were part of transcription factors binding sites, potentially involved in modulating the LALBA gene expression. The LALBA genotype affected renneting properties (P < 0.001), as heterozygotes c.-358CT and c.-163GA were characterised by delayed rennet coagulation time and curd firming time and the lowest value of curd firmness. The present investigation increases the panel of SNPs and adds new information about the effects of the caprine LALBA gene polymorphism.

Characterization of the complete mitochondrial genome of Acanthoscelides obtectus (Coleoptera: Chrysomelidae: Bruchinae) with phylogenetic analysis.

PubMed

Yao, Jie; Yang, Hong; Dai, Renhuai

2017-10-01

Acanthoscelides obtectus is a common species of the subfamily Bruchinae and a worldwide-distributed seed-feeding beetle. The complete mitochondrial genome of A. obtectus is 16,130 bp in length with an A + T content of 76.4%. It contains a positive AT skew and a negative GC skew. The mitogenome of A. obtectus contains 13 protein-coding genes (PCGs), 22 tRNA genes, two rRNA genes and a non-coding region (D-loop). All PCGs start with an ATN codon, and seven (ND3, ATP6, COIII, ND3, ND4L, ND6, and Cytb) of them terminate with TAA, while the remaining five (COI, COII, ND1, ND4, and ND5) terminate with a single T, ATP8 terminates with TGA. Except tRNA Ser , the secondary structures of 21 tRNAs that can be folded into a typical clover-leaf structure were identified. The secondary structures of lrRNA and srRNA were also predicted in this study. There are six domains with 48 helices in lrRNA and three domains with 32 helices in srRNA. The control region of A. obtectus is 1354 bp in size with the highest A + T content (83.5%) in a mitochondrial gene. Thirteen PCGs in 19 species have been used to infer their phylogenetic relationships. Our results show that A. obtectus belongs to the family Chrysomelidae (subfamily-Bruchinae). This is the first study on phylogenetic analyses involving the mitochondrial genes of A. obtectus and could provide basic data for future studies of mitochondrial genome diversities and the evolution of related insect lineages.

Fast-Running Aeroelastic Code Based on Unsteady Linearized Aerodynamic Solver Developed

NASA Technical Reports Server (NTRS)

Reddy, T. S. R.; Bakhle, Milind A.; Keith, T., Jr.

2003-01-01

The NASA Glenn Research Center has been developing aeroelastic analyses for turbomachines for use by NASA and industry. An aeroelastic analysis consists of a structural dynamic model, an unsteady aerodynamic model, and a procedure to couple the two models. The structural models are well developed. Hence, most of the development for the aeroelastic analysis of turbomachines has involved adapting and using unsteady aerodynamic models. Two methods are used in developing unsteady aerodynamic analysis procedures for the flutter and forced response of turbomachines: (1) the time domain method and (2) the frequency domain method. Codes based on time domain methods require considerable computational time and, hence, cannot be used during the design process. Frequency domain methods eliminate the time dependence by assuming harmonic motion and, hence, require less computational time. Early frequency domain analyses methods neglected the important physics of steady loading on the analyses for simplicity. A fast-running unsteady aerodynamic code, LINFLUX, which includes steady loading and is based on the frequency domain method, has been modified for flutter and response calculations. LINFLUX, solves unsteady linearized Euler equations for calculating the unsteady aerodynamic forces on the blades, starting from a steady nonlinear aerodynamic solution. First, we obtained a steady aerodynamic solution for a given flow condition using the nonlinear unsteady aerodynamic code TURBO. A blade vibration analysis was done to determine the frequencies and mode shapes of the vibrating blades, and an interface code was used to convert the steady aerodynamic solution to a form required by LINFLUX. A preprocessor was used to interpolate the mode shapes from the structural dynamic mesh onto the computational dynamics mesh. Then, we used LINFLUX to calculate the unsteady aerodynamic forces for a given mode, frequency, and phase angle. A postprocessor read these unsteady pressures and calculated the generalized aerodynamic forces, eigenvalues, and response amplitudes. The eigenvalues determine the flutter frequency and damping. As a test case, the flutter of a helical fan was calculated with LINFLUX and compared with calculations from TURBO-AE, a nonlinear time domain code, and from ASTROP2, a code based on linear unsteady aerodynamics.

Refraction of the principal stress trajectories and the stress jumps on faults and contact surfaces: Part 1. Non-constrained regular trajectories

NASA Astrophysics Data System (ADS)

Mukhamediev, Sh. A.

2014-09-01

Rock masses contain ubiquitous multiscale heterogeneities, which (or whose boundaries) serve as the surfaces of discontinuity for some characteristics of the stress state, e.g., for the orientation of principal stress axes. Revealing the regularities that control these discontinuities is a key to understanding the processes taking place at the boundaries of the heterogeneities and for designing the correct procedures for reconstructing and theoretical modeling of tectonic stresses. In the present study, the local laws describing the refraction of the axes of extreme principal stresses T 1 (maximal tension in the deviatoric sense) and T 3 (maximal compression) of the Cauchy stress tensor at the transition over the elementary area n of discontinuity whose orientation is specified by the unit normal n are derived. It is assumed that on the area n of discontinuity, frictional contact takes place. No hypotheses are made on the constitutive equations, and a priori constraints are not posed on the orientation on the stress axes. Two domains, which adjoin area n on the opposite sides and are conventionally marked + and -, are distinguished. In the case of the two-dimensional (2D) stress state, any principal stress axis on passing from domain - to domain + remains in the same quadrant of the plane as the continuation of this axis in domain +. The sign and size of the refraction angle depend on the sign and amplitude of the jump of the normal stress, which is tangential to the surface of discontinuity. In the three-dimensional (3D) case, the refraction of axes T 1 and T 3 should be analyzed simultaneously. For each side, + and -, the projections of the T 1 and T 3 axes on the generally oriented plane n form the shear sectors S + and S -, which are determined unambiguously and to whose angular domains the possible directions p + and p - of the shear stress vectors belong. In order for the extreme stress axes T {1/+}, T {3/+} and T {1/-}, T {3/-} to be statically compatible on the generally oriented plane n, it is required that sectors S + and S - had a nonempty intersection. The direction vectors p + and p - are determined uniquely if, besides axes T {1/-}, T {3/-} and T {1/+}, T {3/+}, also the ratios of differential stresses R + and R - (0 ≤ R ± ≤ 1) are known. This is equivalent to specifying the reduced stress tensors T {/R +} and T {/R -} The necessary condition for tensors T {/R +} and T {/R -} being statically compatible on plane n is the equality p + = p -. In this paper, simple methods are suggested for solving the inverse problem of constructing the set of the orientations of the extreme stress axes from the known direction p of the shear stress vector on plane n and from the data on the shear sector. Based on these methods and using the necessary conditions of local equilibrium on plane n formulated above, all the possible orientations of axes T {1/+}, T {3/+} are determined if the projections of axes T {1/-}, T {3/-} axes on side — are given. The angle between the projections of axes T {1/+}, T {1/-} and/or T {3/+}, T {3/-} on the plane can attain 90°. Besides the general case, also the particular cases of the contact between the degenerate stress states and the special position of plane n relative to the principal stress axes are thoroughly examined. Generalization of the obtained results makes it possible to plot the local diagram of the orientations of axes T {1/+}, T {3/+} for a given sector S -. This diagram is a so-called stress orientation sphere, which is subdivided into three pairs of areas (compression, tension, and compression-extension). The tension and compression zones cannot contain the poles of T {3/+} and T {1/+} axes, respectively. The compression-extension zones can contain the poles of either T {1/+} or T {3/+} axis but not both poles simultaneously. In the particular case when the shear stress vector has a unique direction p - on side -, the areas of compression-extension disappear and the diagram is reduced to a beach-ball plot, which visualizes the focal mechanism solution of an earthquake. If area n is a generally oriented plane and if the orientation of the pairs of the statically compatible axes T {1/-}, T {3/-} and T {1/+}, T {3/+} is specified, then, the stress values on side + are uniquely determined from the known stress values on side -. From the value of differential stress ratio R -, one can calculate the value of R +, and using the values of the principal stresses on side -, determine the total stress tensor T + on side +. The obtained results are supported by the laboratory experiments and drilling data. In particular, these results disclose the drawbacks of some established notions and methods in which the possible refraction of the stress axes is unreasonably ignored or taken into account improperly. For example, it is generally misleading to associate the slip on the preexisting fault with the orientation of any particular trihedron of the principal stress axes. The reconstruction should address the potentially statically compatible principal stress axes, which are differently oriented on opposite sides of the fault plane. The fact that, based on the orientation of the intraplate principal stresses at the base of the lithosphere, one cannot make a conclusion on the active or passive influence of the mantle flows on the lithospheric plate motion is another example. The present relationships linking the stress values on the opposite sides of the fault plane on which the orientations of the principal stress axes are known demonstrate the incorrectness of the existing methods, in which the reduced stress tensors within the material domains are reconstructed without allowance for the dynamic interaction of these domains with their neighbors. In addition, using the obtained results, one can generalize the notion of the zone of dynamical control of a fault onto the case of the existence of discontinuities in this region and analyze the stress transfer across the system of the faults.

A Center for Advanced Electrical and Structural Polymers

DTIC Science & Technology

1988-10-31

REPORT I 3b. TIME COVERED 14. DATE OF REPORT (Year, Month, Oay) IS. PAGE COUNT Final j FROM TO 44 16. SUPPLEMENTARY NOTATION 17. COSATI CODES 18...Banhegyi Dr. N. Easwar Dr. Z. Chai Dr. K. Liang Dr. S. Choe Dr. G. Smyth Dr. P. Cifra Dr. J . Kim Dr. W. Huh Dr. Q. Bhatia Dr. J . Grobelny Dr. P... J . Chen (WSU) Dr. G. Quin Dr. M. Sinksy (WSU) Dr. N. Segudovic Dr. R. Miller (WSU) Dr. G. Shy Dr. Y. Gur Mr. L. Wu Dr. T. Bleha Dr. A. Sikora Dr. H

Cytochrome P450BM-3 reduces aldehydes to alcohols through a direct hydride transfer

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

Kaspera, Ruediger; Sahele, Tariku; Lakatos, Kyle

Highlights: Black-Right-Pointing-Pointer Cytochrome P450BM-3 reduced aldehydes to alcohols efficiently (k{sub cat} {approx} 25 min{sup -1}). Black-Right-Pointing-Pointer Reduction is a direct hydride transfer from R-NADP{sup 2}H to the carbonyl moiety. Black-Right-Pointing-Pointer P450 domain variants enhance reduction through potential allosteric/redox interactions. Black-Right-Pointing-Pointer Novel reaction will have implications for metabolism of xenobiotics. -- Abstract: Cytochrome P450BM-3 catalyzed the reduction of lipophilic aldehydes to alcohols efficiently. A k{sub cat} of {approx}25 min{sup -1} was obtained for the reduction of methoxy benzaldehyde with wild type P450BM-3 protein which was higher than in the isolated reductase domain (BMR) alone and increased in specific P450-domain variants. Themore » reduction was caused by a direct hydride transfer from preferentially R-NADP{sup 2}H to the carbonyl moiety of the substrate. Weak substrate-P450-binding of the aldehyde, turnover with the reductase domain alone, a deuterium incorporation in the product from NADP{sup 2}H but not D{sub 2}O, and no inhibition by imidazole suggests the reductase domain of P450BM-3 as the potential catalytic site. However, increased aldehyde reduction by P450 domain variants (P450BM-3 F87A T268A) may involve allosteric or redox mechanistic interactions between heme and reductase domains. This is a novel reduction of aldehydes by P450BM-3 involving a direct hydride transfer and could have implications for the metabolism of endogenous substrates or xenobiotics.« less

System and method for constructing filters for detecting signals whose frequency content varies with time

DOEpatents

Qian, Shie; Dunham, Mark E.

1996-01-01

A system and method for constructing a bank of filters which detect the presence of signals whose frequency content varies with time. The present invention includes a novel system and method for developing one or more time templates designed to match the received signals of interest and the bank of matched filters use the one or more time templates to detect the received signals. Each matched filter compares the received signal x(t) with a respective, unique time template that has been designed to approximate a form of the signals of interest. The robust time domain template is assumed to be of the order of w(t)=A(t)cos{2.pi..phi.(t)} and the present invention uses the trajectory of a joint time-frequency representation of x(t) as an approximation of the instantaneous frequency function {.phi.'(t). First, numerous data samples of the received signal x(t) are collected. A joint time frequency representation is then applied to represent the signal, preferably using the time frequency distribution series (also known as the Gabor spectrogram). The joint time-frequency transformation represents the analyzed signal energy at time t and frequency .function., P(t,f), which is a three-dimensional plot of time vs. frequency vs. signal energy. Then P(t,f) is reduced to a multivalued function f(t), a two dimensional plot of time vs. frequency, using a thresholding process. Curve fitting steps are then performed on the time/frequency plot, preferably using Levenberg-Marquardt curve fitting techniques, to derive a general instantaneous frequency function .phi.'(t) which best fits the multivalued function f(t), a trajectory of the joint time-frequency domain representation of x(t). Integrating .phi.'(t) along t yields .phi.(t), which is then inserted into the form of the time template equation. A suitable amplitude A(t) is also preferably determined. Once the time template has been determined, one or more filters are developed which each use a version or form of the time template.

Cell-penetrable mouse forkhead box protein 3 alleviates experimental arthritis in mice by up-regulating regulatory T cells.

PubMed

Liu, Xia; Ji, Baoju; Sun, Mengyi; Wu, Weijiang; Huang, Lili; Sun, Aihua; Zong, Yangyong; Xia, Sheng; Shi, Liyun; Qian, Hui; Xu, Wenrong; Shao, Qixiang

2015-07-01

Regulatory T cells (T(regs)) have potential applications in clinical disease therapy, such as autoimmune diseases and transplant rejection. However, their numbers are limited. Forkhead box protein 3 (FoxP3) is a key transcription factor that controls T(reg) development and function. Here, we generated a cell-permeable fusion protein, protein transduction domain (PTD)-conjugated mouse FoxP3 protein (PTD-mFoxP3), and evaluated whether PTD-mFoxp3 can alleviate rheumatoid arthritis (RA) in the collagen-induced arthritis (CIA) mouse model. As expected, PTD-mFoxP3 was transduced into cells effectively, and inhibited T cell activation and attenuated the cell proliferation. It decreased interleukin (IL) 2 and interferon (IFN)-γ expression, and increased IL-10 expression in activated CD4(+)CD25(-) T cells. PTD-mFoxP3-transduced CD4(+)CD25(-) T cells attenuated proliferation of activated CD4(+)CD25(-) T cells. In addition, PTD-mFoxP3 blocked the Th17 differentiation programme in vitro and down-regulated IL-17 production from T cells by modulating induction and levels of retinoid-related orphan receptor gamma t (RORγt). Intra-articular delivery of PTD-mFoxP3 delayed disease incidence remarkably and alleviated autoimmune symptoms of CIA mice. Moreover, protective effects of PTD-mFoxP3 were associated with regulating the balance of T helper type 17 (Th17) and T(regs). These results suggest that PTD-mFoxP3 may be a candidate for RA therapy. © 2015 British Society for Immunology.

Temperature and electric-field induced phase transitions, and full tensor properties of [011] C-poled domain-engineered tetragonal 0 .63 Pb (M g1 /3N b2 /3) -0 .37 PbTi O3 single crystals

NASA Astrophysics Data System (ADS)

Zheng, Limei; Jing, Yujia; Lu, Xiaoyan; Wang, Ruixue; Liu, Gang; Lü, Weiming; Zhang, Rui; Cao, Wenwu

2016-03-01

The phase-transition sequence of 0.67 Pb (M g1 /3N b2 /3)- 0.37 PbTi O3 (PMN-0.37PT) single crystals driven by the electric (E ) field and temperature is comprehensively studied. Based on the strain-E field loop, polarization-E field loop, and the evolution of domain configurations, the E field along the [011] C induced phase transitions have been confirmed to be as follows: tetragonal (T ) → monoclinic (MC)→ single domain orthorhombic (O ) phase. As the E field decreases, the induced O phase cannot be maintained and transformed to the MC phase, then to the coexistence state of MC and T phases. In addition, the complete sets of dielectric, piezoelectric, and elastic constants for the [011] C-poled domain-engineered PMN-0.37PT single crystal were measured at room temperature, which show high longitudinal dielectric, piezoelectric, and electromechanical properties (ɛ33T=10 661 ,d33=1052 pC /N , and k33= 0.766 ). Our results revealed that the MC phase plays an important role in the high electromechanical properties of this domain-engineered single crystal. The temperature dependence of the domain configuration revealed that the volume fraction of the MC phase decreases with temperature accompanied by the reduction of ɛ33T,d31, and k31 due to the substantially smaller intrinsic properties of the T phase.

Energy dynamics and current sheet structure in fluid and kinetic simulations of decaying magnetohydrodynamic turbulence

DOE PAGES

Makwana, K. D.; Zhdankin, V.; Li, H.; ...

2015-04-10

We performed simulations of decaying magnetohydrodynamic (MHD) turbulence with a fluid and a kinetic code. The initial condition is an ensemble of long-wavelength, counter-propagating, shear-Alfvén waves, which interact and rapidly generate strong MHD turbulence. The total energy is conserved and the rate of turbulent energy decay is very similar in both codes, although the fluid code has numerical dissipation, whereas the kinetic code has kinetic dissipation. The inertial range power spectrum index is similar in both the codes. The fluid code shows a perpendicular wavenumber spectral slope of k-1.3⊥k⊥-1.3. The kinetic code shows a spectral slope of k-1.5⊥k⊥-1.5 for smallermore » simulation domain, and k-1.3⊥k⊥-1.3 for larger domain. We then estimate that collisionless damping mechanisms in the kinetic code can account for the dissipation of the observed nonlinear energy cascade. Current sheets are geometrically characterized. Their lengths and widths are in good agreement between the two codes. The length scales linearly with the driving scale of the turbulence. In the fluid code, their thickness is determined by the grid resolution as there is no explicit diffusivity. In the kinetic code, their thickness is very close to the skin-depth, irrespective of the grid resolution. Finally, this work shows that kinetic codes can reproduce the MHD inertial range dynamics at large scales, while at the same time capturing important kinetic physics at small scales.« less

Energy dynamics and current sheet structure in fluid and kinetic simulations of decaying magnetohydrodynamic turbulence

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

Makwana, K. D.; Zhdankin, V.; Li, H.

We performed simulations of decaying magnetohydrodynamic (MHD) turbulence with a fluid and a kinetic code. The initial condition is an ensemble of long-wavelength, counter-propagating, shear-Alfvén waves, which interact and rapidly generate strong MHD turbulence. The total energy is conserved and the rate of turbulent energy decay is very similar in both codes, although the fluid code has numerical dissipation, whereas the kinetic code has kinetic dissipation. The inertial range power spectrum index is similar in both the codes. The fluid code shows a perpendicular wavenumber spectral slope of k-1.3⊥k⊥-1.3. The kinetic code shows a spectral slope of k-1.5⊥k⊥-1.5 for smallermore » simulation domain, and k-1.3⊥k⊥-1.3 for larger domain. We then estimate that collisionless damping mechanisms in the kinetic code can account for the dissipation of the observed nonlinear energy cascade. Current sheets are geometrically characterized. Their lengths and widths are in good agreement between the two codes. The length scales linearly with the driving scale of the turbulence. In the fluid code, their thickness is determined by the grid resolution as there is no explicit diffusivity. In the kinetic code, their thickness is very close to the skin-depth, irrespective of the grid resolution. Finally, this work shows that kinetic codes can reproduce the MHD inertial range dynamics at large scales, while at the same time capturing important kinetic physics at small scales.« less

Multivariate assessment of event-related potentials with the t-CWT method.

PubMed

Bostanov, Vladimir

2015-11-05

Event-related brain potentials (ERPs) are usually assessed with univariate statistical tests although they are essentially multivariate objects. Brain-computer interface applications are a notable exception to this practice, because they are based on multivariate classification of single-trial ERPs. Multivariate ERP assessment can be facilitated by feature extraction methods. One such method is t-CWT, a mathematical-statistical algorithm based on the continuous wavelet transform (CWT) and Student's t-test. This article begins with a geometric primer on some basic concepts of multivariate statistics as applied to ERP assessment in general and to the t-CWT method in particular. Further, it presents for the first time a detailed, step-by-step, formal mathematical description of the t-CWT algorithm. A new multivariate outlier rejection procedure based on principal component analysis in the frequency domain is presented as an important pre-processing step. The MATLAB and GNU Octave implementation of t-CWT is also made publicly available for the first time as free and open source code. The method is demonstrated on some example ERP data obtained in a passive oddball paradigm. Finally, some conceptually novel applications of the multivariate approach in general and of the t-CWT method in particular are suggested and discussed. Hopefully, the publication of both the t-CWT source code and its underlying mathematical algorithm along with a didactic geometric introduction to some basic concepts of multivariate statistics would make t-CWT more accessible to both users and developers in the field of neuroscience research.

Al 1s-2p absorption spectroscopy of shock-wave heating and compression in laser-driven planar foil

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

Sawada, H.; Regan, S. P.; Radha, P. B.

Time-resolved Al 1s-2p absorption spectroscopy is used to diagnose direct-drive, shock-wave heating and compression of planar targets having nearly Fermi-degenerate plasma conditions (T{sub e}{approx}10-40 eV, {rho}{approx}3-11 g/cm{sup 3}) on the OMEGA Laser System [T. R. Boehly et al., Opt. Commun. 133, 495 (1997)]. A planar plastic foil with a buried Al tracer layer was irradiated with peak intensities of 10{sup 14}-10{sup 15} W/cm{sup 2} and probed with the pseudocontinuum M-band emission from a point-source Sm backlighter in the range of 1.4-1.7 keV. The laser ablation process launches 10-70 Mbar shock waves into the CH/Al/CH target. The Al 1s-2p absorption spectramore » were analyzed using the atomic physic code PRISMSPECT to infer T{sub e} and {rho} in the Al layer, assuming uniform plasma conditions during shock-wave heating, and to determine when the heat front penetrated the Al layer. The drive foils were simulated with the one-dimensional hydrodynamics code LILAC using a flux-limited (f=0.06 and f=0.1) and nonlocal thermal-transport model [V. N. Goncharov et al., Phys. Plasmas 13, 012702 (2006)]. The predictions of simulated shock-wave heating and the timing of heat-front penetration are compared to the observations. The experimental results for a wide variety of laser-drive conditions and buried depths have shown that the LILAC predictions using f=0.06 and the nonlocal model accurately model the shock-wave heating and timing of the heat-front penetration while the shock is transiting the target. The observed discrepancy between the measured and simulated shock-wave heating at late times of the drive can be explained by the reduced radiative heating due to lateral heat flow in the corona.« less

The interplay between tissue plasminogen activator domains and fibrin structures in the regulation of fibrinolysis: kinetic and microscopic studies

PubMed Central

Thelwell, Craig; Williams, Stella C.; Silva, Marta M. C. G.; Szabó, László; Kolev, Krasimir

2011-01-01

Regulation of tissue-type plasminogen activator (tPA) depends on fibrin binding and fibrin structure. tPA structure/function relationships were investigated in fibrin formed by high or low thrombin concentrations to produce a fine mesh and small pores, or thick fibers and coarse structure, respectively. Kinetics studies were performed to investigate plasminogen activation and fibrinolysis in the 2 types of fibrin, using wild-type tPA (F-G-K1-K2-P, F and K2 binding), K1K1-tPA (F-G-K1-K1-P, F binding), and delF-tPA (G-K1-K2-P, K2 binding). There was a trend of enzyme potency of tPA > K1K1-tPA > delF-tPA, highlighting the importance of the finger domain in regulating activity, but the differences were less apparent in fine fibrin. Fine fibrin was a better surface for plasminogen activation but more resistant to lysis. Scanning electron and confocal microscopy using orange fluorescent fibrin with green fluorescent protein-labeled tPA variants showed that tPA was strongly associated with agglomerates in coarse but not in fine fibrin. In later lytic stages, delF-tPA-green fluorescent protein diffused more rapidly through fibrin in contrast to full-length tPA, highlighting the importance of finger domain-agglomerate interactions. Thus, the regulation of fibrinolysis depends on the starting nature of fibrin fibers and complex dynamic interaction between tPA and fibrin structures that vary over time. PMID:20966169

Fault Specific Seismic Hazard Maps as Input to Loss Reserves Calculation for Attica Buildings

NASA Astrophysics Data System (ADS)

Deligiannakis, Georgios; Papanikolaou, Ioannis; Zimbidis, Alexandros; Roberts, Gerald

2014-05-01

Greece is prone to various natural disasters, such as wildfires, floods, landslides and earthquakes, due to the special environmental and geological conditions dominating in tectonic plate boundaries. Seismic is the predominant risk, in terms of damages and casualties in the Greek territory. The historical record of earthquakes in Greece has been published from various researchers, providing useful data in seismic hazard assessment of Greece. However, the completeness of the historical record in Greece, despite being one of the longest worldwide, reaches only 500 years for M ≥ 7.3 and less than 200 years for M ≥ 6.5. Considering that active faults in the area have recurrence intervals of a few hundred to several thousands of years, it is clear that many active faults have not been activated during the completeness period covered by the historical records. New Seismic Hazard Assessment methodologies tend to follow fault specific approaches where seismic sources are geologically constrained active faults, in order to address problems related to the historical records incompleteness, obtain higher spatial resolution and calculate realistic source locality distances, since seismic sources are very accurately located. Fault specific approaches provide quantitative assessments as they measure fault slip rates from geological data, providing a more reliable estimate of seismic hazard. We used a fault specific seismic hazard assessment approach for the region of Attica. The method of seismic hazard mapping from geological fault throw-rate data combined three major factors: Empirical data which combine fault rupture lengths, earthquake magnitudes and coseismic slip relationships. The radiuses of VI, VII, VIII and IX isoseismals on the Modified Mercalli (MM) intensity scale. Attenuation - amplification functions for seismic shaking on bedrock compared to basin filling sediments. We explicitly modeled 22 active faults that could affect the region of Attica, including Athens, using detailed data derived from published papers, neotectonic maps and fieldwork observations. Moreover, we incorporated background seismicity models from the historic record and also the subduction zone earthquakes distribution, for the integration of strong deep earthquakes that could also affect Attica region. We created 4 high spatial resolution seismic hazard maps for the region of Attica, one for each of the intensities VII - X (MM). These maps offer a locality specific shaking recurrence record, which represents the long-term shaking record in a more complete way, since they incorporate several seismic cycles of the active faults that could affect Attica. Each one of these high resolution seismic hazard maps displays both the spatial distribution and the recurrence, over a specific time period, of the relevant intensity. Time - independent probabilities were extracted based on these average recurrence intervals, using the stationary Poisson model P = 1 -e-Λt. The 'Λ' value was provided by the intensities recurrence, as displayed in the seismic hazard maps. However, the insurance contracts usually lack of detailed spatial information and they refer to Postal Codes level, akin to CRESTA zones. To this end, a time-independent probability of shaking at intensities VII - X was calculated for every Postal Code, for a given time period, using the Poisson model. The reserves calculation on buildings portfolio combines the probability of events of specific intensities within the Postal Codes, with the buildings characteristics, such as the building construction type and the insured value. We propose a standard approach for the reserves calculation K(t) for a specific time period: K (t) = x2 ·[x1 ·y1 ·P1(t) + x1 ·y2 ·P2(t) + x1 ·y3 ·P3(t) + x1 ·y4 ·P4(t)] x1 which is a function of the probabilities of occurrence for the seismic intensities VII - X (P1(t) -P4(t)) for the same period, the value of the building x1, the insured value x2 and the characteristics of the building, such as the construction type, age, height and use of property (y1 - y4). Furthermore a stochastic approach is also adopted in order to obtain the relevant reserve value K(t) for the specific time period. This calculation considers a set of simulations from the Poisson random variable and then taking the respective expectations.

The Detection and Discrimination of Small Munitions using Giant Magnetoresistive (OMR) Sensors

DTIC Science & Technology

2010-09-01

Suffield, Canada. McGlone, D.T., 1998, Magnetometer Comparison Smoke Creek Instruments’ GMR SCIMAG- 01 & Bartington Fluxgate MAG-03MC70, A...a magnetometer and frequency domain or time domain electromagnetic induction sensor. Both the Honeywell and NVE GlvlR sensors studied have si.m ilar...field sensor. In p0ssive mode, the GMR sensor, which has a resolution of Jess than l 0 nT, perfom1ed similarly to a cesium vapor magnetometer . When

Computational Electronics and Electromagnetics

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

DeFord, J.F.

The Computational Electronics and Electromagnetics thrust area is a focal point for computer modeling activities in electronics and electromagnetics in the Electronics Engineering Department of Lawrence Livermore National Laboratory (LLNL). Traditionally, they have focused their efforts in technical areas of importance to existing and developing LLNL programs, and this continues to form the basis for much of their research. A relatively new and increasingly important emphasis for the thrust area is the formation of partnerships with industry and the application of their simulation technology and expertise to the solution of problems faced by industry. The activities of the thrust areamore » fall into three broad categories: (1) the development of theoretical and computational models of electronic and electromagnetic phenomena, (2) the development of useful and robust software tools based on these models, and (3) the application of these tools to programmatic and industrial problems. In FY-92, they worked on projects in all of the areas outlined above. The object of their work on numerical electromagnetic algorithms continues to be the improvement of time-domain algorithms for electromagnetic simulation on unstructured conforming grids. The thrust area is also investigating various technologies for conforming-grid mesh generation to simplify the application of their advanced field solvers to design problems involving complicated geometries. They are developing a major code suite based on the three-dimensional (3-D), conforming-grid, time-domain code DSI3D. They continue to maintain and distribute the 3-D, finite-difference time-domain (FDTD) code TSAR, which is installed at several dozen university, government, and industry sites.« less

Implementation and Characterization of Three-Dimensional Particle-in-Cell Codes on Multiple-Instruction-Multiple-Data Massively Parallel Supercomputers

NASA Technical Reports Server (NTRS)

Lyster, P. M.; Liewer, P. C.; Decyk, V. K.; Ferraro, R. D.

1995-01-01

A three-dimensional electrostatic particle-in-cell (PIC) plasma simulation code has been developed on coarse-grain distributed-memory massively parallel computers with message passing communications. Our implementation is the generalization to three-dimensions of the general concurrent particle-in-cell (GCPIC) algorithm. In the GCPIC algorithm, the particle computation is divided among the processors using a domain decomposition of the simulation domain. In a three-dimensional simulation, the domain can be partitioned into one-, two-, or three-dimensional subdomains ("slabs," "rods," or "cubes") and we investigate the efficiency of the parallel implementation of the push for all three choices. The present implementation runs on the Intel Touchstone Delta machine at Caltech; a multiple-instruction-multiple-data (MIMD) parallel computer with 512 nodes. We find that the parallel efficiency of the push is very high, with the ratio of communication to computation time in the range 0.3%-10.0%. The highest efficiency (> 99%) occurs for a large, scaled problem with 64(sup 3) particles per processing node (approximately 134 million particles of 512 nodes) which has a push time of about 250 ns per particle per time step. We have also developed expressions for the timing of the code which are a function of both code parameters (number of grid points, particles, etc.) and machine-dependent parameters (effective FLOP rate, and the effective interprocessor bandwidths for the communication of particles and grid points). These expressions can be used to estimate the performance of scaled problems--including those with inhomogeneous plasmas--to other parallel machines once the machine-dependent parameters are known.

Architecture for time or transform domain decoding of reed-solomon codes

NASA Technical Reports Server (NTRS)

Hsu, In-Shek (Inventor); Truong, Trieu-Kie (Inventor); Deutsch, Leslie J. (Inventor); Shao, Howard M. (Inventor)

1989-01-01

Two pipeline (255,233) RS decoders, one a time domain decoder and the other a transform domain decoder, use the same first part to develop an errata locator polynomial .tau.(x), and an errata evaluator polynominal A(x). Both the time domain decoder and transform domain decoder have a modified GCD that uses an input multiplexer and an output demultiplexer to reduce the number of GCD cells required. The time domain decoder uses a Chien search and polynomial evaluator on the GCD outputs .tau.(x) and A(x), for the final decoding steps, while the transform domain decoder uses a transform error pattern algorithm operating on .tau.(x) and the initial syndrome computation S(x), followed by an inverse transform algorithm in sequence for the final decoding steps prior to adding the received RS coded message to produce a decoded output message.

The Purification of the Chlamydomonas reinhardtii chloroplast ClpP complex: additional subunits and structural features

PubMed Central

Derrien, Benoît; Majeran, Wojciech; Effantin, Grégory; Ebenezer, Joseph; Friso, Giulia; van Wijk, Klaas J.; Steven, Alasdair C.; Maurizi, Michael R.; Vallon, Olivier

2012-01-01

The ClpP peptidase is a major constituent of the proteolytic machinery of bacteria and organelles. The chloroplast ClpP complex is unusual, in that it associates a large number of subunits, one of which (ClpP1) is encoded in the chloroplast, the others in the nucleus. The complexity of these large hetero-oligomeric complexes has been a major difficulty in their overproduction and biochemical characterization. In this paper, we describe the purification of native chloroplast ClpP complex from the green alga Chlamydomonas reinhardtii, using a strain that carries the Strep-tag II at the C-terminus of the ClpP1 subunit. Similar to land plants, the algal complex comprises active and inactive subunits (3 ClpP and 5 ClpR, respectively). Evidence is presented that a sub-complex can be produced by dissociation, comprising ClpP1 and ClpR1, 2, 3 and 4, similar to the ClpR-ring described in land plants. Our Chlamydomonas ClpP preparation also contains two ClpT subunits, ClpT3 and ClpT4, which like the land plant ClpT1 and ClpT2 show 2 Clp-N domains. ClpTs are believed to function in substrate binding and/or assembly of the two heptameric rings. Phylogenetic analysis indicates that ClpT subunits have appeared independently in Chlorophycean algae, in land plants and in dispersed cyanobacterial genomes. Negative staining electron microscopy shows that the Chlamydomonas complex retains the barrel-like shape of homo-oligomeric ClpPs, with 4 additional peripheral masses that we speculate represent either the additional IS1 domain of ClpP1 (a feature unique to algae) or ClpTs or extensions of ClpR subunits PMID:22772861

Understanding of Materials State and its Degradation using Non-Linear Ultrasound (NLU) Approaches - Phase 3

DTIC Science & Technology

2013-05-31

j] (11) A MATLAB code was written for finding the displacement at each node for all time steps. Material selected for the study was steel with 1 m...some of the dislocations are annihilated or rearranged. Various stages in the recovery are, entanglement of dislocations, cell formation, annihilation...frequency domain using an in-house pro- gram written in MATLAB . A time-domain signal obtained from nonlinear measurement and its corresponding fast

Compressive Strength Estimation of Marble Specimens using Acoustic Emission Hits in Time and Natural Time Domains: Preliminary Results

NASA Astrophysics Data System (ADS)

Hloupis, George; Stavrakas, Ilias; Vallianatos, Filippos; Triantis, Dimos

2013-04-01

The current study deals with preliminary results of characteristic patterns derived from acoustic emissions during compressional stress. Two loading cycles were applied to a specimen of 4cm x 4cm x 10 cm Dionysos marble while acoustic emissions (AE) were recorded using one acoustic sensor coupled at the expected direction of the main crack (at the center of the specimen). The produced time series comprised from the number of counts per AE hit under increasing and constant load. Processing took place in two domains: in conventional time domain (t), using multiresolution wavelet analysis for the study of temporal variation of the wavelet-coefficients' standard deviation (SDEV) [1] and in natural time domain (χ), using the variance (κ1) of natural-time transformed time-series [2,3]. Results in both cases, dictate that identification of the region where the increasing stress (σ), exceeds 40% of the ultimate compressional strength (σ*), is possible. More specific, in conventional time domain, the temporal evolution of SDEV presents a sharp change around σ* during first loading cycle and less than σ* during second loading cycle. In natural time domain, the κ1 value clearly oscillate around 0.07 at natural time indexes corresponding to σ* during first loading cycle. Merging both results leads to a preliminary observation that we have an identification of the time when the compressional stress exceeds σ*. References [1] Telesca, L., Hloupis, G., Nikolintaga, I., Vallianatos, F.,."Temporal patterns in southern Aegean seismicity revealed by the multiresolution wavelet analysis", Communications in Nonlinear Science and Numerical Simulation, vol. 12, issue 8, pp 1418-1426, 2007 [2] P. A. Varotsos, N. V. Sarlis, and E. S. Skordas, "Natural Time Analysis: The New View of Time. Precursory Seismic Electric Signals, Earthquakes and other Complex Time-Series", Springer-Verlag, Berlin, Heidelberg, 2011. [3] N. V. Sarlis, P. A. Varotsos, and E. S. Skordas, "Flux Avalances in YBa2Cu307-x films and rice piles: natural time domain analysis", Physical Review B, 73, 054504, 2006. Acknowledgements This work was supported by the THALES Program of the Ministry of Education of Greece and the European Union in the framework of the project entitled "Integrated understanding of Seismicity, using innovative Methodologies of Fracture mechanics along with Earthquake and non extensive statistical physics - Application to the geodynamic system of the Hellenic Arc. SEISMO FEAR HELLARC".

Capacity for cooperative binding of thyroid hormone (T3) receptor dimers defines wild type T3 response elements.

PubMed

Brent, G A; Williams, G R; Harney, J W; Forman, B M; Samuels, H H; Moore, D D; Larsen, P R

1992-04-01

Thyroid hormone response elements (T3REs) have been identified in a variety of promoters including those directing expression of rat GH (rGH), alpha-myosin heavy chain (rMHC), and malic enzyme (rME). A detailed biochemical and genetic analysis of the rGH element has shown that it consists of three hexamers related to the consensus [(A/G)GGT(C/A)A]. We have extended this analysis to the rMHC and rME elements. Binding of highly purified thyroid hormone receptor (T3R) to T3REs was determined using the gel shift assay, and thyroid hormone (T3) induction was measured in transient tranfections. We show that the wild type version of each of the three elements binds T3R dimers cooperatively. Mutational analysis of the rMHC and rME elements identified domains important for binding T3R dimers and allowed a direct determination of the relationship between T3R binding and function. In each element two hexamers are required for dimer binding, and mutations that interfere with dimer formation significantly reduce T3 induction. Similar to the rGH element, the rMHC T3RE contains three hexameric domains arranged as a direct repeat followed by an inverted copy, although the third domain is weaker than in rGH. All three are required for full function and T3R binding. The rME T3RE is a two-hexamer direct repeat T3RE, which also binds T3R monomer and dimer. Across a series of mutant elements, there was a strong correlation between dimer binding in vitro and function in vivo for rMHC (r = 0.99, P less than 0.01) and rME (r = 0.67, P less than 0.05) T3REs. Our results demonstrate a similar pattern of T3R dimer binding to a diverse array of hexameric sequences and arrangements in three wild type T3REs. Addition of nuclear protein enhanced T3R binding but did not alter the specificity of binding to wild type or mutant elements. Binding of purified T3R to T3REs was highly correlated with function, both with and without the addition of nuclear protein. T3R dimer formation is the common feature which defines the capacity of these elements to confer T3 induction.

Data and code for the exploratory data analysis of the electrical energy demand in the time domain in Greece.

PubMed

Tyralis, Hristos; Karakatsanis, Georgios; Tzouka, Katerina; Mamassis, Nikos

2017-08-01

We present data and code for visualizing the electrical energy data and weather-, climate-related and socioeconomic variables in the time domain in Greece. The electrical energy data include hourly demand, weekly-ahead forecasted values of the demand provided by the Greek Independent Power Transmission Operator and pricing values in Greece. We also present the daily temperature in Athens and the Gross Domestic Product of Greece. The code combines the data to a single report, which includes all visualizations with combinations of all variables in multiple time scales. The data and code were used in Tyralis et al. (2017) [1].

AN OVERVIEW OF EPANET VERSION 3.0

EPA Science Inventory

EPANET is a widely used public domain software package for modeling the hydraulic and water quality behavior of water distribution systems over an extended period of time. The last major update to the code was version 2.0 released in 2000 (Rossman, 2000). Since that time there ha...

CD6 and Linker of Activated T Cells are Potential Interaction Partners for T Cell-Specific Adaptor Protein.

PubMed

Hem, C D; Ekornhol, M; Granum, S; Sundvold-Gjerstad, V; Spurkland, A

2017-02-01

The T cell-specific adaptor protein (TSAd) contains several protein interaction domains, and is merging as a modulator of T cell activation. Several interaction partners for the TSAd proline-rich region and phosphotyrosines have been identified, including the Src and Tec family kinases lymphocyte-specific protein tyrosine kinase and interleukin 2-inducible T cell kinase. Via its Src homology 2 (SH2) domain, TSAd may thus function as a link between these enzymes and other signalling molecules. However, few binding partners to the TSAd SH2 domain in T cells are hitherto known. Through the use of in silico ligand prediction, peptide spot arrays, pull-down and immunoprecipitation experiments, we here report novel interactions between the TSAd SH2 domain and CD6 phosphotyrosine (pTyr) 629 and linker of activated T cells (LAT) pTyr 171 , pTyr 191 and pTyr 226 . © 2016 The Foundation for the Scandinavian Journal of Immunology.

Characterization of the Ruler Protein Interaction Interface on the Substrate Specificity Switch Protein in the Yersinia Type III Secretion System*

PubMed Central

Ho, Oanh; Rogne, Per; Edgren, Tomas; Wolf-Watz, Hans; Login, Frédéric H.; Wolf-Watz, Magnus

2017-01-01

Many pathogenic Gram-negative bacteria use the type III secretion system (T3SS) to deliver effector proteins into eukaryotic host cells. In Yersinia, the switch to secretion of effector proteins is induced first after intimate contact between the bacterium and its eukaryotic target cell has been established, and the T3SS proteins YscP and YscU play a central role in this process. Here we identify the molecular details of the YscP binding site on YscU by means of nuclear magnetic resonance (NMR) spectroscopy. The binding interface is centered on the C-terminal domain of YscU. Disrupting the YscU-YscP interaction by introducing point mutations at the interaction interface significantly reduced the secretion of effector proteins and HeLa cell cytotoxicity. Interestingly, the binding of YscP to the slowly self-cleaving YscU variant P264A conferred significant protection against autoproteolysis. The YscP-mediated inhibition of YscU autoproteolysis suggests that the cleavage event may act as a timing switch in the regulation of early versus late T3SS substrates. We also show that YscUC binds to the inner rod protein YscI with a dissociation constant (Kd) of 3.8 μm and with 1:1 stoichiometry. The significant similarity among different members of the YscU, YscP, and YscI families suggests that the protein-protein interactions discussed in this study are also relevant for other T3SS-containing Gram-negative bacteria. PMID:28039361

Modeling and inversion Matlab algorithms for resistivity, induced polarization and seismic data

NASA Astrophysics Data System (ADS)

Karaoulis, M.; Revil, A.; Minsley, B. J.; Werkema, D. D.

2011-12-01

M. Karaoulis (1), D.D. Werkema (3), A. Revil (1,2), A., B. Minsley (4), (1) Colorado School of Mines, Dept. of Geophysics, Golden, CO, USA. (2) ISTerre, CNRS, UMR 5559, Université de Savoie, Equipe Volcan, Le Bourget du Lac, France. (3) U.S. EPA, ORD, NERL, ESD, CMB, Las Vegas, Nevada, USA . (4) USGS, Federal Center, Lakewood, 10, 80225-0046, CO. Abstract We propose 2D and 3D forward modeling and inversion package for DC resistivity, time domain induced polarization (IP), frequency-domain IP, and seismic refraction data. For the resistivity and IP case, discretization is based on rectangular cells, where each cell has as unknown resistivity in the case of DC modelling, resistivity and chargeability in the time domain IP modelling, and complex resistivity in the spectral IP modelling. The governing partial-differential equations are solved with the finite element method, which can be applied to both real and complex variables that are solved for. For the seismic case, forward modeling is based on solving the eikonal equation using a second-order fast marching method. The wavepaths are materialized by Fresnel volumes rather than by conventional rays. This approach accounts for complicated velocity models and is advantageous because it considers frequency effects on the velocity resolution. The inversion can accommodate data at a single time step, or as a time-lapse dataset if the geophysical data are gathered for monitoring purposes. The aim of time-lapse inversion is to find the change in the velocities or resistivities of each model cell as a function of time. Different time-lapse algorithms can be applied such as independent inversion, difference inversion, 4D inversion, and 4D active time constraint inversion. The forward algorithms are benchmarked against analytical solutions and inversion results are compared with existing ones. The algorithms are packaged as Matlab codes with a simple Graphical User Interface. Although the code is parallelized for multi-core cpus, it is not as fast as machine code. In the case of large datasets, someone should consider transferring parts of the code to C or Fortran through mex files. This code is available through EPA's website on the following link http://www.epa.gov/esd/cmb/GeophysicsWebsite/index.html Although this work was reviewed by EPA and approved for publication, it may not necessarily reflect official Agency policy.

Energy balance in TM-1-MH Tokamak (ohmical heating)

NASA Astrophysics Data System (ADS)

Stoeckel, J.; Koerbel, S.; Kryska, L.; Kopecky, V.; Dadalec, V.; Datlov, J.; Jakubka, K.; Magula, P.; Zacek, F.; Pereverzev, G. V.

1981-10-01

Plasma in the TM-1-MH Tokamak was experimentally studied in the parameter range: tor. mg. field B = 1,3 T, plasma current I sub p = 14 kA, electron density N sub E 3.10 to the 19th power cubic meters. The two numerical codes are available for the comparison with experimental data. TOKATA-code solves simplified energy balance equations for electron and ion components. TOKSAS-code solves the detailed energy balance of the ion component.

Implementation of a handheld electronic point-of-care billing system improved efficiency in the critical care unit.

PubMed

Fahy, Brenda G; Ketzler, Jonathan T

2007-01-01

Coding and billing are time consuming and important considerations for critical care practitioners. A 1-year prospective, observational study incorporated the use of a personal digital assistant and MDeverywhere software (Hauppauge, New York) for patient coding and billing. Twelve months of data were examined before electronic implementation (pre-elec) and compared with a 12-month period after implementation (post-elec) by using an unpaired t test or z test with P < .05 considered significant. The total number of charges was 2479 pre-elec and 2243 post-elec. The days from date of service to billing for services significantly decreased from 37.8 pre-elec to 12.4 post-elec (P < .001); days in accounts receivable significantly decreased from 92.0 to 73.0 (P < .001). The net collection rate increased from 44.7% pre-elec to 49.3% post-elec (P < .001). Duplicate charges significantly decreased from 5.0% pre-elec to 1.4% post-elec ( P < .001). The return on investment was 1.97-fold (197%). The initiation of personal digital assistant technology to facilitate billing and coding resulted in significant improvements.

An Evolution Operator Solution for a Nonlinear Beam Equation

DTIC Science & Technology

1990-12-01

Press, Orlando, FL , 1975. 2. H. Beirio Da Veiga . Kato’s perturbation theory and well-posedness for the Euler equa- tions in bounded domains. Archive...2)vIIx < E. (90) From the definitions IIA5(tl)v - As(t 2)vIIx = 0 00 (h(t) - P(t2 ))D 4 V2 = 0)( (f(tl) - f3(t2))D4 V2 ) =I P~h) - fl (i 2) I (j1(D4...P(t + h) - fl (t))D~v2 0) h-.O i+- t D4v2 0= (93) Since 1P’ is continuous and D 4v 2 does not depend on t it is now clear that As(t)v is contin

The two single nucleotide polymorphisms in the H37/RBM5 tumour suppressor gene at 3p21.3 correlated with different subtypes of non-small cell lung cancers

PubMed Central

Oh, Juliana J.; Koegel, Ashley; Phan, Diana T.; Razfar, Ali; Slamon, Dennis J.

2007-01-01

Summary Allele loss and genetic alteration in chromosome 3p, particularly in 3p21.3 region, are the most frequent and the earliest genomic abnormalities found in lung cancer. Multiple 3p21.3 genes exhibit various degrees of tumour suppression activity suggesting that 3p21.3 genes may function as an integrated tumour suppressor region through their diverse biological activities. We have previously demonstrated growth inhibitory effects and tumour suppression mechanism of the H37/RBM5 gene which is one of the 19 genes residing in the 370kb minimal overlap region at 3p21.3. In the current study, in an attempt to find, if any, mutations in the H37 coding region in lung cancer cells, we compared nucleotide sequences of the entire H37 gene in tumour vs. adjacent normal tissues from 17 non-small cell lung cancer (NSCLC) patients. No mutations were detected, instead, we found the two silent single nucleotide polymorphisms (SNPs), C1138T and C2185T, within the coding region of the H37 gene. In addition, we found that specific allele types at these SNP positions are correlated with different histological subtypes of NSCLC; tumours containing heterozygous alleles (C+T) at these SNP positions are more likely to be associated with adenocarcinoma (AC) whereas homozygous alleles (either C or T) are associated with squamous cell carcinoma (SCC) (p=0.0098). We postulate that, these two silent polymorphisms may be in linkage disequilibrium (LD) with a disease causative allele in the 3p21.3 tumour suppressor region which is packed with a large number of important genes affecting lung cancer development. In addition, because of prevalent loss of heterozygosity (LOH) detected at 3p21.3 which precedes lung cancer initiation, these SNPs may be developed into a marker screening for the high risk individuals. PMID:17606309

Defect-phase-dynamics approach to statistical domain-growth problem of clock models

NASA Technical Reports Server (NTRS)

Kawasaki, K.

1985-01-01

The growth of statistical domains in quenched Ising-like p-state clock models with p = 3 or more is investigated theoretically, reformulating the analysis of Ohta et al. (1982) in terms of a phase variable and studying the dynamics of defects introduced into the phase field when the phase variable becomes multivalued. The resulting defect/phase domain-growth equation is applied to the interpretation of Monte Carlo simulations in two dimensions (Kaski and Gunton, 1983; Grest and Srolovitz, 1984), and problems encountered in the analysis of related Potts models are discussed. In the two-dimensional case, the problem is essentially that of a purely dissipative Coulomb gas, with a sq rt t growth law complicated by vertex-pinning effects at small t.

Characterization of activating mutations of NOTCH3 in T-cell acute lymphoblastic leukemia and anti-leukemic activity of NOTCH3 inhibitory antibodies.

PubMed

Bernasconi-Elias, P; Hu, T; Jenkins, D; Firestone, B; Gans, S; Kurth, E; Capodieci, P; Deplazes-Lauber, J; Petropoulos, K; Thiel, P; Ponsel, D; Hee Choi, S; LeMotte, P; London, A; Goetcshkes, M; Nolin, E; Jones, M D; Slocum, K; Kluk, M J; Weinstock, D M; Christodoulou, A; Weinberg, O; Jaehrling, J; Ettenberg, S A; Buckler, A; Blacklow, S C; Aster, J C; Fryer, C J

2016-11-24

Notch receptors have been implicated as oncogenic drivers in several cancers, the most notable example being NOTCH1 in T-cell acute lymphoblastic leukemia (T-ALL). To characterize the role of activated NOTCH3 in cancer, we generated an antibody that detects the neo-epitope created upon gamma-secretase cleavage of NOTCH3 to release its intracellular domain (ICD3), and sequenced the negative regulatory region (NRR) and PEST (proline, glutamate, serine, threonine) domain coding regions of NOTCH3 in a panel of cell lines. We also characterize NOTCH3 tumor-associated mutations that result in activation of signaling and report new inhibitory antibodies. We determined the structural basis for receptor inhibition by obtaining the first co-crystal structure of a NOTCH3 antibody with the NRR protein and defined two distinct epitopes for NRR antibodies. The antibodies exhibit potent anti-leukemic activity in cell lines and tumor xenografts harboring NOTCH3 activating mutations. Screening of primary T-ALL samples reveals that 2 of 40 tumors examined show active NOTCH3 signaling. We also identified evidence of NOTCH3 activation in 12 of 24 patient-derived orthotopic xenograft models, 2 of which exhibit activation of NOTCH3 without activation of NOTCH1. Our studies provide additional insights into NOTCH3 activation and offer a path forward for identification of cancers that are likely to respond to therapy with NOTCH3 selective inhibitory antibodies.

Characterization of activating mutations of NOTCH3 in T cell acute lymphoblastic leukemia and anti-leukemic activity of NOTCH3 inhibitory antibodies

PubMed Central

Bernasconi-Elias, Paula; Hu, Tiancen; Jenkins, David; Firestone, Brant; Gans, Sara; Kurth, Esther; Capodieci, Paola; Deplazes-Lauber, Joelle; Petropoulos, Konstantin; Thiel, Phillip; Ponsel, Dirk; Choi, Sung Hee; LeMotte, Peter; London, Anne; Goetcshkes, Margaret; Nolin, Erin; Jones, Michael D.; Slocum, Kelly; Kluk, Michael J.; Weinstock, David M.; Christodoulou, Alexandra; Weinberg, Olga; Jaehrling, Jan; Ettenberg, Seth A.; Buckler, Alan; Blacklow, Stephen C.; Aster, Jon C.; Fryer, Christy J.

2016-01-01

Notch receptors have been implicated as oncogenic drivers in several cancers, the most notable example being NOTCH1 in T-cell acute lymphoblastic leukemia (T-ALL). To characterize the role of activated NOTCH3 in cancer, we generated an antibody that detects the neo-epitope created upon gamma-secretase cleavage of NOTCH3 to release its intracellular domain (ICD3), and sequenced the negative regulatory region (NRR) and PEST domain coding regions of NOTCH3 in a panel of cell lines. We also characterize NOTCH3 tumor-associated mutations that result in activation of signaling and report new inhibitory antibodies. We determined the structural basis for receptor inhibition by obtaining the first co-crystal structure of a NOTCH3 antibody with the NRR protein and defined two distinct epitopes for NRR antibodies. The antibodies exhibit potent anti-leukemic activity in cell lines and tumor xenografts harboring NOTCH3 activating mutations. Screening of primary T-ALL samples reveals that two of 40 tumors examined show active NOTCH3 signaling. We also identified evidence of NOTCH3 activation in 12 of 24 patient-derived orthotopic xenograft models, two of which exhibit activation of NOTCH3 without activation of NOTCH1. Our studies provide additional insights into NOTCH3 activation and offer a path forward for identification of cancers that are likely to respond to therapy with NOTCH3 selective inhibitory antibodies. PMID:27157619

DCOMP Award Lecture (Metropolis): A 3D Spectral Anelastic Hydrodynamic Code for Shearing, Stratified Flows

NASA Astrophysics Data System (ADS)

Barranco, Joseph

2006-03-01

We have developed a three-dimensional (3D) spectral hydrodynamic code to study vortex dynamics in rotating, shearing, stratified systems (eg, the atmosphere of gas giant planets, protoplanetary disks around newly forming protostars). The time-independent background state is stably stratified in the vertical direction and has a unidirectional linear shear flow aligned with one horizontal axis. Superposed on this background state is an unsteady, subsonic flow that is evolved with the Euler equations subject to the anelastic approximation to filter acoustic phenomena. A Fourier-Fourier basis in a set of quasi-Lagrangian coordinates that advect with the background shear is used for spectral expansions in the two horizontal directions. For the vertical direction, two different sets of basis functions have been implemented: (1) Chebyshev polynomials on a truncated, finite domain, and (2) rational Chebyshev functions on an infinite domain. Use of this latter set is equivalent to transforming the infinite domain to a finite one with a cotangent mapping, and using cosine and sine expansions in the mapped coordinate. The nonlinear advection terms are time integrated explicitly, whereas the Coriolis force, buoyancy terms, and pressure/enthalpy gradient are integrated semi- implicitly. We show that internal gravity waves can be damped by adding new terms to the Euler equations. The code exhibits excellent parallel performance with the Message Passing Interface (MPI). As a demonstration of the code, we simulate vortex dynamics in protoplanetary disks and the Kelvin-Helmholtz instability in the dusty midplanes of protoplanetary disks.

Determining mode excitations of vacuum electronics devices via three-dimensional simulations using the SOS code

NASA Technical Reports Server (NTRS)

Warren, Gary

1988-01-01

The SOS code is used to compute the resonance modes (frequency-domain information) of sample devices and separately to compute the transient behavior of the same devices. A code, DOT, is created to compute appropriate dot products of the time-domain and frequency-domain results. The transient behavior of individual modes in the device is then plotted. Modes in a coupled-cavity traveling-wave tube (CCTWT) section excited beam in separate simulations are analyzed. Mode energy vs. time and mode phase vs. time are computed and it is determined whether the transient waves are forward or backward waves for each case. Finally, the hot-test mode frequencies of the CCTWT section are computed.

Exome sequencing identifies variants in two genes encoding the LIM-proteins NRAP and FHL1 in an Italian patient with BAG3 myofibrillar myopathy.

PubMed

D'Avila, Francesca; Meregalli, Mirella; Lupoli, Sara; Barcella, Matteo; Orro, Alessandro; De Santis, Francesca; Sitzia, Clementina; Farini, Andrea; D'Ursi, Pasqualina; Erratico, Silvia; Cristofani, Riccardo; Milanesi, Luciano; Braga, Daniele; Cusi, Daniele; Poletti, Angelo; Barlassina, Cristina; Torrente, Yvan

2016-06-01

Myofibrillar myopathies (MFMs) are genetically heterogeneous dystrophies characterized by the disintegration of Z-disks and myofibrils and are associated with mutations in genes encoding Z-disk or Z-disk-related proteins. The c.626 C > T (p.P209L) mutation in the BAG3 gene has been described as causative of a subtype of MFM. We report a sporadic case of a 26-year-old Italian woman, affected by MFM with axonal neuropathy, cardiomyopathy, rigid spine, who carries the c.626 C > T mutation in the BAG3 gene. The patient and her non-consanguineous healthy parents and brother were studied with whole exome sequencing (WES) to further investigate the genetic basis of this complex phenotype. In the patient, we found that the BAG3 mutation is associated with variants in the NRAP and FHL1 genes that encode muscle-specific, LIM domain containing proteins. Quantitative real time PCR, immunohistochemistry and Western blot analysis of the patient's muscular biopsy showed the absence of NRAP expression and FHL1 accumulation in aggregates in the affected skeletal muscle tissue. Molecular dynamic analysis of the mutated FHL1 domain showed a modification in its surface charge, which could affect its capability to bind its target proteins. To our knowledge this is the first study reporting, in a BAG3 MFM, the simultaneous presence of genetic variants in the BAG3 and FHL1 genes (previously described as independently associated with MFMs) and linking the NRAP gene to MFM for the first time.

Structure and Function of the Splice Variants of TMPRSS2-ERG, a Prevalent Genomic Alteration in Prostate Cancer

DTIC Science & Technology

2009-09-01

binding ETS domain) and five type II (without ETS domain). Fusion-positive type I– and type II–containing phages were amplified with T3 and T7 primers...will be performed to identify the authentic 3’ UTRs from the mRNA pool from CaP patient specimens. Using phage excision strategy, we will use to... phage DNA sequences plasmids (cDNA) clones were generated by using phage excision strategy. Figure 1. ERG splice variants in prostate cancer

Complete mitochondrial genome sequence from an endangered Indian snake, Python molurus molurus (Serpentes, Pythonidae).

PubMed

Dubey, Bhawna; Meganathan, P R; Haque, Ikramul

2012-07-01

This paper reports the complete mitochondrial genome sequence of an endangered Indian snake, Python molurus molurus (Indian Rock Python). A typical snake mitochondrial (mt) genome of 17258 bp length comprising of 37 genes including the 13 protein coding genes, 22 tRNA genes, and 2 ribosomal RNA genes along with duplicate control regions is described herein. The P. molurus molurus mt. genome is relatively similar to other snake mt. genomes with respect to gene arrangement, composition, tRNA structures and skews of AT/GC bases. The nucleotide composition of the genome shows that there are more A-C % than T-G% on the positive strand as revealed by positive AT and CG skews. Comparison of individual protein coding genes, with other snake genomes suggests that ATP8 and NADH3 genes have high divergence rates. Codon usage analysis reveals a preference of NNC codons over NNG codons in the mt. genome of P. molurus. Also, the synonymous and non-synonymous substitution rates (ka/ks) suggest that most of the protein coding genes are under purifying selection pressure. The phylogenetic analyses involving the concatenated 13 protein coding genes of P. molurus molurus conformed to the previously established snake phylogeny.

49 CFR 565.25 - Content requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... for VIN Year Code 1980 A 1981 B 1982 C 1983 D 1984 E 1985 F 1986 G 1987 H 1988 J 1989 K 1990 L 1991 M 1992 N 1993 P 1994 R 1995 S 1996 T 1997 V 1998 W 1999 X 2000 Y 2001 1 2002 2 2003 3 2004 4 2005 5 2006... J = 1 K = 2 L = 3 M = 4 N = 5 P = 7 R = 9 S = 2 T = 3 U = 4 V = 5 W = 6 X = 7 Y = 8 Z = 9 (2...

Specific phosphopeptide binding regulates a conformational change in the PI 3-kinase SH2 domain associated with enzyme activation.

PubMed Central

Shoelson, S E; Sivaraja, M; Williams, K P; Hu, P; Schlessinger, J; Weiss, M A

1993-01-01

SH2 (src-homology 2) domains define a newly recognized binding motif that mediates the physical association of target phosphotyrosyl proteins with downstream effector enzymes. An example of such phosphoprotein-effector coupling is provided by the association of phosphatidylinositol 3-kinase (PI 3-kinase) with specific phosphorylation sites within the PDGF receptor, the c-Src/polyoma virus middle T antigen complex and the insulin receptor substrate IRS-1. Notably, phosphoprotein association with the SH2 domains of p85 also stimulates an increase in catalytic activity of the PI 3-kinase p110 subunit, which can be mimicked by phosphopeptides corresponding to targeted phosphoprotein phosphorylation sites. To investigate how phosphoprotein binding to the p85 SH2 domain stimulates p110 catalytic activation, we have examined the differential effects of phosphotyrosine and PDGF receptor-, IRS-1- and c-Src-derived phosphopeptides on the conformation of an isolated SH2 domain of PI 3-kinase. Although phosphotyrosine and both activating and non-activating phosphopeptides bind to the SH2 domain, activating phosphopeptides bind with higher affinity and induce a qualitatively distinct conformational change as monitored by CD and NMR spectroscopy. Amide proton exchange and protease protection assays further show that high affinity, specific phosphopeptide binding induces non-local dynamic SH2 domain stabilization. Based on these findings we propose that specific phosphoprotein binding to the p85 subunit induces a change in SH2 domain structure which is transmitted to the p110 subunit and regulates enzymatic activity by an allosteric mechanism. Images PMID:8382612

[Effect of extracts from Dendrobii ifficinalis flos on hyperthyroidism Yin deficiency mice].

PubMed

Lei, Shan-shan; Lv, Gui-yuan; Jin, Ze-wu; Li, Bo; Yang, Zheng-biao; Chen, Su-hong

2015-05-01

Some unhealthy life habits, such as long-term smoking, heavy drinking, sexual overstrain and frequent stay-up could induce the Yin deficiency symptoms of zygomatic red and dysphoria. Stems of Dendrobii officinalis flos (DOF) showed the efficacy of nourishing Yin. In this study, the hyperthyroidism Yin deficiency model was set up to study the yin nourishing effect and action mechanism of DOF, in order to provide the pharmacological basis for developing DOF resources and decreasing resource wastes. ICR mice were divided into five groups: the normal control group, the model control group, the positive control group and DOF extract groups (6.4 g · kg(-1)). Except for the normal group, the other groups were administrated with thyroxine for 30 d to set up the hyperthyroidism yin deficiency model. At the same time, the other groups were administrated with the corresponding drugs for 30 d. After administration for 4 weeks, the signs (facial temperature, pain domain, heart rate and autonomic activity) in mice were measured, and the facial and ear micro-circulation blood flow were detected by laser Doppler technology. After the last administration, all mice were fasted for 12 hours, blood were collected from their orbits, and serum were separated to detect AST, ALT, TG and TP by the automatic biochemistry analyzer and test T3, T4 and TSH levels by ELISA. (1) Compared with the normal control group, the model control group showed significant increases in facial and ear micro-circulation blood flow, facial temperature and heart rate (P < 0.05, P < 0.01), serum AST, ALT (P < 0.01), T3 level (P < 0.05), TSH level (P < 0.05) and notable deceases in pain domain (P < 0.01), TG level (P < 0.01). (2) Compared with the model control group, extracts from DOF (6 g · kg(-1)) could notably reduce facial and ear micro-circulation blood flow, facial temperature and heart rate (P < 0.05, P < 0.01) and AST (P < 0.05) and enhance pain domain (P < 0.01) and TG (P < 0.01). Extracts from DOF (4 g · kg(-1)) could remarkably reduce AST and ALT levels (P < 0.01, 0.05). Extracts from DOF (6 g · kg(-1) 4 g · kg(-1)) could significantly reduce T3 and increase serum TSH level (P < 0.05). DOF could improve Yin deficiency symptoms of zygomatic red and dysphoria in mice as well as liver function injury caused by overactive thyroid axis. According to its action mechanism, DOF may show yin nourishing and hepatic protective effects by impacting thyroxin substance metabolism, improving micro-circulation and reducing heart rate.

Low pH-Induced Pore Formation by the T Domain of Botulinum Toxin Type A is Dependent upon NaCl Concentration

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

Lai, B.; Swaminathan, S.; Agarwal, R.

2010-07-19

Botulinum neurotoxins (BoNTs) undergo low pH-triggered membrane insertion, resulting in the translocation of their light (catalytic) chains into the cytoplasm. The T (translocation) domain of the BoNT heavy chain is believed to carry out translocation. Here, the behavior of isolated T domain from BoNT type A has been characterized, both in solution and when associated with model membranes. When BoNT T domain prepared in the detergent dodecylmaltoside was diluted into aqueous solution, it exhibited a low pH-dependent conformational change below pH 6. At low pH the T domain associated with, and formed pores within, model membrane vesicles composed of 30more » mol% dioleoylphosphatidylglycerol/70 mol% dioleoylphosphatidylcholine. Although T domain interacted with vesicles at low (50 mM) and high (400 mM) NaCl concentrations, the interaction required much less lipid at low salt. However, even at high lipid concentrations pore formation was much more pronounced at low NaCl concentrations than at high NaCl concentration. Increasing salt concentration after insertion in the presence of 50 mM NaCl did not decrease pore formation. A similar effect of NaCl concentration upon pore formation was observed in vesicles composed solely of dioleoylphosphatidylcholine, showing that the effect of NaCl did not solely involve modulation of electrostatic interactions between protein and anionic lipids. These results indicate that some feature of membrane-bound T domain tertiary structure critical for pore formation is highly dependent upon salt concentration.« less

The C-terminal fragment of parathyroid hormone-related peptide promotes bone formation in diabetic mice with low-turnover osteopaenia

PubMed Central

Lozano, D; Fernández-de-Castro, L; Portal-Núñez, S; López-Herradón, A; Dapía, S; Gómez-Barrena, E; Esbrit, P

2011-01-01

BACKGROUND AND PURPOSE Current data suggest that parathyroid hormone (PTH)-related peptide (PTHrP) domains other than the N-terminal PTH-like domain contribute to its role as an endogenous bone anabolic factor. PTHrP-107-139 inhibits bone resorption, a fact which has precluded an unequivocal demonstration of its possible anabolic action in vivo. We thus sought to characterize the osteogenic effects of this peptide using a mouse model of diabetic low-turnover osteopaenia. EXPERIMENTAL APPROACH PTHrP-107-139 was administered to streptozotocin-induced diabetic mice, with or without bone marrow ablation, for 13 days. Osteopaenia was confirmed by dual-energy X-ray absorptiometry and microcomputed tomography analysis. Histological analysis was performed on paraffin-embedded bone tissue sections by haematoxylin/eosin and Masson's staining, and tartrate-resistent acid phosphatase immunohistochemistry. Mouse bone marrow stromal cells and osteoblastic MC3T3-E1 cells were cultured in normal and/or high glucose (HG) medium. Osteogenic and adipogenic markers were assessed by real-time PCR, and PTHrP and the PTH1 receptor protein expression by Western blot analysis. KEY RESULTS PTHrP-107-139 reversed the alterations in bone structure and osteoblast function, and also promoted bone healing after marrow ablation without affecting the number of osteoclast-like cells in diabetic mice. This peptide also reversed the high-glucose-induced changes in osteogenic differentiation in both bone marrow stromal cells and the more differentiated MC3T3-E1 cells. CONCLUSIONS AND IMPLICATIONS These findings demonstrate that PTHrP-107-139 promotes bone formation in diabetic mice. This mouse model and in vitro cell cultures allowed us to identify various anabolic effects of this peptide in this scenario. PMID:21175568

X-ray crystal structure of the passenger domain of plasmid encoded toxin(Pet), an autotransporter enterotoxin from enteroaggregative Escherichia coli (EAEC)

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

Domingo Meza-Aguilar, J.; Laboratorio de Patogenicidad Bacteriana, Unidad de Hemato Oncología e Investigación, Hospital Infantil de México Federico Gómez 06720, D.F.; Fromme, Petra

Highlights: • X-ray crystal structure of the passenger domain of Plasmid encoded toxin at 2.3 Å. • Structural differences between Pet passenger domain and EspP protein are described. • High flexibility of the C-terminal beta helix is structurally assigned. - Abstract: Autotransporters (ATs) represent a superfamily of proteins produced by a variety of pathogenic bacteria, which include the pathogenic groups of Escherichia coli (E. coli) associated with gastrointestinal and urinary tract infections. We present the first X-ray structure of the passenger domain from the Plasmid-encoded toxin (Pet) a 100 kDa protein at 2.3 Å resolution which is a cause ofmore » acute diarrhea in both developing and industrialized countries. Pet is a cytoskeleton-altering toxin that induces loss of actin stress fibers. While Pet (pdb code: 4OM9) shows only a sequence identity of 50% compared to the closest related protein sequence, extracellular serine protease plasmid (EspP) the structural features of both proteins are conserved. A closer structural look reveals that Pet contains a β-pleaded sheet at the sequence region of residues 181–190, the corresponding structural domain in EspP consists of a coiled loop. Secondary, the Pet passenger domain features a more pronounced beta sheet between residues 135 and 143 compared to the structure of EspP.« less

xRRM

PubMed Central

Singh, Mahavir; Choi, Charles P.; Feigon, Juli

2013-01-01

Genuine La and La-related proteins group 7 (LARP7) bind to the non-coding RNAs transcribed by RNA polymerase III (RNAPIII), which end in UUU-3′OH. The La motif and RRM1 of these proteins (the La module) cooperate to bind the UUU-3′OH, protecting the RNA from degradation, while other domains may be important for RNA folding or other functions. Among the RNAPIII transcripts is ciliate telomerase RNA (TER). p65, a member of the LARP7 family, is an integral Tetrahymena thermophila telomerase holoenzyme protein required for TER biogenesis and telomerase RNP assembly. p65, together with TER and telomerase reverse transcriptase (TERT), form the Tetrahymena telomerase RNP catalytic core. p65 has an N-terminal domain followed by a La module and a C-terminal domain, which binds to the TER stem 4. We recently showed that the p65 C-terminal domain harbors a cryptic, atypical RRM, which uses a unique mode of single- and double-strand RNA binding and is required for telomerase RNP catalytic core assembly. This domain, which we named xRRM, appears to be present in and unique to genuine La and LARP7 proteins. Here we review the structure of the xRRM, discuss how this domain could recognize diverse substrates of La and LARP7 proteins and discuss the functional implications of the xRRM as an RNP chaperone. PMID:23328630

Early Consequences of Pectus Excavatum Surgery on Self-Esteem and General Quality of Life.

PubMed

Zuidema, W P; Oosterhuis, J W A; Zijp, G W; van der Heide, S M; van der Steeg, A F W; van Heurn, L W E

2018-02-06

An early observation after chest wall correction is direct inspection from the PE patient of their "new" thorax. Changes in self-perception may give raise to other psychological adaptations. The aim of this study was to evaluate the early changes in the fields of self-esteem, body image and QoL. Prospective observational longitudinal multicenter cohort study. Self-esteem, emotional limitations and general health were assessed using the Child Health Questionnaire (CHQ) in patients under 18 and the World Health Organization Quality of Life Questionnaire-bref (WHOQOL-bref) was used for body image, psychological domain and overall QoL in patients over 16 years of age. Measurements were taken before surgery (T1) and 6 weeks (T2), and 6 months thereafter (T3). Scores on post-operative self-esteem were significantly higher compared with scores pre-operatively (p < 0.007). Also body image, psychological domain and emotional limitations showed significant improvement, respectively p < 0.001, p < 0.001, and p < 0.016. Significant improvement in the first three components was mainly achieved in the first 6 weeks post-operative. In emotional limitation, however, the largest change was between 6 weeks and 6 months. Overall quality of life in the WHOQOL-bref and general health domain in the CHQ showed no significant improvement in relation to the pre-operative scores. Post-operative PE patients after Nuss procedure showed an improved body image, increased self-esteem and increased psychological resilience in the first 6 months, with the most marked change in the first 6 weeks. Also emotional limitations changed significantly over time. The changes were not large enough to influence general QoL or general health significantly.

Design and isolation of ribozyme-substrate pairs using RNase P-based ribozymes containing altered substrate binding sites.

PubMed Central

Mobley, E M; Pan, T

1999-01-01

Substrate recognition and cleavage by the bacterial RNase P RNA requires two domains, a specificity domain, or S-domain, and a catalytic domain, or C-domain. The S-domain binds the T stem-loop region in a pre-tRNA substrate to confer specificity for tRNA substrates. In this work, the entire S-domain of the Bacillus subtilis RNase P RNA is replaced with an artificial substrate binding module. New RNA substrates are isolated by in vitro selection using two libraries containing random regions of 60 nt. At the end of the selection, the cleavage rates of the substrate library are approximately 0.7 min(-1)in 10 mM MgCl(2)at 37 degrees C, approximately 4-fold better than the cleavage of a pre-tRNA substrate by the wild-type RNase P RNA under the same conditions. The contribution of the S-domain replacement to the catalytic efficiency is from 6- to 22 000-fold. Chemical and nuclease mapping of two ribozyme-product complexes shows that this contribution correlates with direct interactions between the S-domain replacement and the selected substrate. These results demonstrate the feasibility of design and isolation of RNase P-based, matching ribozyme-substrate pairs without prior knowledge of the sequence or structure of the interactive modules in the ribozyme or substrate. PMID:10518624

Increased production of soluble CTLA-4 in patients with spondylarthropathies correlates with disease activity

PubMed Central

Toussirot, Éric; Saas, Philippe; Deschamps, Marina; Pouthier, Fabienne; Perrot, Lucille; Perruche, Sylvain; Chabod, Jacqueline; Tiberghien, Pierre; Wendling, Daniel

2009-01-01

Introduction Spondylarthropathies (SpA) are characterized by abnormal immune responses including T cell activation. Cytotoxic T lymphocyte associated molecule-4 (CTLA-4) is involved in down-regulating immune responses. A soluble form of CTLA-4 (sCTLA-4), resulting from an alternative splicing, has been identified and was found increased in several autoimmune diseases. Here, we evaluated circulating levels of sCTLA-4 as a marker of immune dysregulation in SpA. Intracellular CTLA-4 and levels of CTLA-4 transcript expression in peripheral blood lymphocytes (PBL) were also studied. Methods Sera from 165 patients with SpA were evaluated for sCTLA-4 measurements. Results were compared with those from 71 patients with rheumatoid arthritis (RA) and 88 healthy subjects. In 32 patients with SpA, 22 patients with RA and 15 healthy controls, we analyzed the intracellular CTLA-4 expression in CD4+ T cells, CD8+ T cells, activated (HLA-DR+Foxp3-) CD4+ T cells, CD4+ regulatory (CD25+Foxp3+) T cells and in CD3 negative cells by flow cytometry. Expression of the full length (coding for membrane CTLA-4) and spliced form (coding for sCTLA-4) of CTLA-4 transcripts in PBL were analyzed by quantitative real-time polymerase chain reaction (QRT-PCR). Results High levels of sCTLA-4 were found in the SpA group compared to the RA group and healthy controls (P < 0.0001). Soluble CTLA-4 serum levels strongly correlated with clinical index of disease activity BASDAI (r = 0.42, P < 0.0001) and C-reactive protein (CRP) levels (r = 0.17, P = 0.037). In contrast to RA patients, SpA patients did not exhibit changes in intracellular CTLA-4 expression in the different PBL subsets tested. Finally, the SpA group showed a preferential expression of the spliced CTLA-4 mRNA (P = 0.0014) in PBL. Conclusions SpA patients exhibit high levels of circulating sCTLA-4 that may result from an alternative splicing of CTLA-4 transcripts. This may influence immune activation and regulation in SpA. PMID:19570209

Molecular dynamics simulation of the structure and dynamics of 5-HT3 serotonin receptor

NASA Astrophysics Data System (ADS)

Antonov, M. Yu.; Popinako, A. V.; Prokopiev, G. A.

2016-10-01

In this work, we investigated structure, dynamics and ion transportation in transmembrane domain of the 5-HT3 serotonin receptor. High-resolution (0.35 nm) structure of the 5-HT3 receptor in complex with stabilizing nanobodies was determined by protein crystallography in 2014 (Protein data bank (PDB) code 4PIR). Transmembrane domain of the structure was prepared in complex with explicit membrane environment (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC)) and solvent (TIP3P water model). Molecular dynamics protocols for simulation and stabilization of the transmembrane domain of the 5-HT3 receptor model were developed and 60 ns simulation of the structure was conducted in order to explore structural parameters of the system. We estimated the mean force profile for Na+ ions using umbrella sampling method.

OSIRIS - an object-oriented parallel 3D PIC code for modeling laser and particle beam-plasma interaction

NASA Astrophysics Data System (ADS)

Hemker, Roy

1999-11-01

The advances in computational speed make it now possible to do full 3D PIC simulations of laser plasma and beam plasma interactions, but at the same time the increased complexity of these problems makes it necessary to apply modern approaches like object oriented programming to the development of simulation codes. We report here on our progress in developing an object oriented parallel 3D PIC code using Fortran 90. In its current state the code contains algorithms for 1D, 2D, and 3D simulations in cartesian coordinates and for 2D cylindrically-symmetric geometry. For all of these algorithms the code allows for a moving simulation window and arbitrary domain decomposition for any number of dimensions. Recent 3D simulation results on the propagation of intense laser and electron beams through plasmas will be presented.

Energy dynamics and current sheet structure in fluid and kinetic simulations of decaying magnetohydrodynamic turbulence

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

Makwana, K. D., E-mail: kirit.makwana@gmx.com; Cattaneo, F.; Zhdankin, V.

Simulations of decaying magnetohydrodynamic (MHD) turbulence are performed with a fluid and a kinetic code. The initial condition is an ensemble of long-wavelength, counter-propagating, shear-Alfvén waves, which interact and rapidly generate strong MHD turbulence. The total energy is conserved and the rate of turbulent energy decay is very similar in both codes, although the fluid code has numerical dissipation, whereas the kinetic code has kinetic dissipation. The inertial range power spectrum index is similar in both the codes. The fluid code shows a perpendicular wavenumber spectral slope of k{sub ⊥}{sup −1.3}. The kinetic code shows a spectral slope of k{submore » ⊥}{sup −1.5} for smaller simulation domain, and k{sub ⊥}{sup −1.3} for larger domain. We estimate that collisionless damping mechanisms in the kinetic code can account for the dissipation of the observed nonlinear energy cascade. Current sheets are geometrically characterized. Their lengths and widths are in good agreement between the two codes. The length scales linearly with the driving scale of the turbulence. In the fluid code, their thickness is determined by the grid resolution as there is no explicit diffusivity. In the kinetic code, their thickness is very close to the skin-depth, irrespective of the grid resolution. This work shows that kinetic codes can reproduce the MHD inertial range dynamics at large scales, while at the same time capturing important kinetic physics at small scales.« less

Magneto-electric Coupling in Domain Engineered Multiferroic Thin Film Heterostructures

DTIC Science & Technology

2014-11-09

J.-G. Yoon, C. B. Eom, J.-S. Chung, T. W. Noh. Step bunching-induced vertical lattice mismatch and crystallographic tilt in vicinal BiFeO[sub 3... piezoelectricity of epitaxial BiFeO3 on SrTiO3 , Appl. Phys. Lett., (02 2012): 62906. doi: 15.00 14.00 13.00 12.00 11.00 10.00 25.00 19.00 20.00...M.V. Holt, S.H. Baek, S.K. Streiffer, P. Baldo, C.B. Eom, P.H. Fuoss. X-ray nanodiffraction of tilted domains in a poled epitaxial BiFeO3 thin film

Anger attacks in bipolar versus recurrent depression.

PubMed

Grover, Sandeep; Painuly, Nitesh; Gupta, Nitin; Mattoo, Surendra K

2011-01-01

Research on anger attacks has been mostly limited to unipolar depression, and only a few studies have focused on anger attacks in bipolar depression. In a cross-sectional study, 22 subjects with bipolar depression were compared to 22 subjects with recurrent unipolar depression using an anger attack questionnaire, irritability, depression and anxiety scale and quality of life scale. Anger attacks were present in 62.5% subjects with recurrent depression (RDD group) compared to 54.5% in subjects with bipolar depression (BD group), but the difference between the groups was not statistically significant. Also, there was no significant difference between the RDD and BD groups on the Irritability Depression and Anxiety Scale and WHOQOL-Bref except that the BD group had a poorer quality of life (QOL) compared to the RDD group in the social relationship domain (t=-2.30, p<0.05). In the BD group, the subjects with anger attacks were older (t=2.77, p<0.05), had significantly higher scores on the Irritability-Outwards component of IDA (t=3.90, p<0.01) and shorter duration of illness (Mann Whitney Signed ranked value 20.00, p<0.01) and duration of treatment (Mann Whitney Signed ranked value 28.00, p<0.05) compared to BD group members without anger attacks. In the RDD group, the subjects with anger attacks had poor QOL in the social domain (t= -2.12, p<0.05), environmental domain (t=2.99, p=.01) and total (t=2.56, p<0.05) QOL compared to those without anger attacks. Anger attacks are equally prevalent in unipolar and bipolar depression, are not influenced by sociodemographic and clinical variables, and lead to comparable impact on the subjective QOL in both groups.

Compressive Coded-Aperture Multimodal Imaging Systems

NASA Astrophysics Data System (ADS)

Rueda-Chacon, Hoover F.

Multimodal imaging refers to the framework of capturing images that span different physical domains such as space, spectrum, depth, time, polarization, and others. For instance, spectral images are modeled as 3D cubes with two spatial and one spectral coordinate. Three-dimensional cubes spanning just the space domain, are referred as depth volumes. Imaging cubes varying in time, spectra or depth, are referred as 4D-images. Nature itself spans different physical domains, thus imaging our real world demands capturing information in at least 6 different domains simultaneously, giving turn to 3D-spatial+spectral+polarized dynamic sequences. Conventional imaging devices, however, can capture dynamic sequences with up-to 3 spectral channels, in real-time, by the use of color sensors. Capturing multiple spectral channels require scanning methodologies, which demand long time. In general, to-date multimodal imaging requires a sequence of different imaging sensors, placed in tandem, to simultaneously capture the different physical properties of a scene. Then, different fusion techniques are employed to mix all the individual information into a single image. Therefore, new ways to efficiently capture more than 3 spectral channels of 3D time-varying spatial information, in a single or few sensors, are of high interest. Compressive spectral imaging (CSI) is an imaging framework that seeks to optimally capture spectral imagery (tens of spectral channels of 2D spatial information), using fewer measurements than that required by traditional sensing procedures which follows the Shannon-Nyquist sampling. Instead of capturing direct one-to-one representations of natural scenes, CSI systems acquire linear random projections of the scene and then solve an optimization algorithm to estimate the 3D spatio-spectral data cube by exploiting the theory of compressive sensing (CS). To date, the coding procedure in CSI has been realized through the use of ``block-unblock" coded apertures, commonly implemented as chrome-on-quartz photomasks. These apertures block or permit to pass the entire spectrum from the scene at given spatial locations, thus modulating the spatial characteristics of the scene. In the first part, this thesis aims to expand the framework of CSI by replacing the traditional block-unblock coded apertures by patterned optical filter arrays, referred as ``color" coded apertures. These apertures are formed by tiny pixelated optical filters, which in turn, allow the input image to be modulated not only spatially but spectrally as well, entailing more powerful coding strategies. The proposed colored coded apertures are either synthesized through linear combinations of low-pass, high-pass and band-pass filters, paired with binary pattern ensembles realized by a digital-micromirror-device (DMD), or experimentally realized through thin-film color-patterned filter arrays. The optical forward model of the proposed CSI architectures will be presented along with the design and proof-of-concept implementations, which achieve noticeable improvements in the quality of the reconstructions compared with conventional block-unblock coded aperture-based CSI architectures. On another front, due to the rich information contained in the infrared spectrum as well as the depth domain, this thesis aims to explore multimodal imaging by extending the range sensitivity of current CSI systems to a dual-band visible+near-infrared spectral domain, and also, it proposes, for the first time, a new imaging device that captures simultaneously 4D data cubes (2D spatial+1D spectral+depth imaging) with as few as a single snapshot. Due to the snapshot advantage of this camera, video sequences are possible, thus enabling the joint capture of 5D imagery. It aims to create super-human sensing that will enable the perception of our world in new and exciting ways. With this, we intend to advance in the state of the art in compressive sensing systems to extract depth while accurately capturing spatial and spectral material properties. The applications of such a sensor are self-evident in fields such as computer/robotic vision because they would allow an artificial intelligence to make informed decisions about not only the location of objects within a scene but also their material properties.

Structural control of caspase-generated glutamyl-tRNA synthetase by appended noncatalytic WHEP domains.

PubMed

Halawani, Dalia; Gogonea, Valentin; DiDonato, Joseph A; Pipich, Vitaliy; Yao, Peng; China, Arnab; Topbas, Celalettin; Vasu, Kommireddy; Arif, Abul; Hazen, Stanley L; Fox, Paul L

2018-06-08

Aminoacyl-tRNA synthetases are ubiquitous, evolutionarily conserved enzymes catalyzing the conjugation of amino acids onto cognate tRNAs. During eukaryotic evolution, tRNA synthetases have been the targets of persistent structural modifications. These modifications can be additive, as in the evolutionary acquisition of noncatalytic domains, or subtractive, as in the generation of truncated variants through regulated mechanisms such as proteolytic processing, alternative splicing, or coding region polyadenylation. A unique variant is the human glutamyl-prolyl-tRNA synthetase (EPRS) consisting of two fused synthetases joined by a linker containing three copies of the WHEP domain (termed by its presence in tryptophanyl-, histidyl-, and glutamyl-prolyl-tRNA synthetases). Here, we identify site-selective proteolysis as a mechanism that severs the linkage between the EPRS synthetases in vitro and in vivo Caspase action targeted Asp-929 in the third WHEP domain, thereby separating the two synthetases. Using a neoepitope antibody directed against the newly exposed C terminus, we demonstrate EPRS cleavage at Asp-929 in vitro and in vivo Biochemical and biophysical characterizations of the N-terminally generated EPRS proteoform containing the glutamyl-tRNA synthetase and most of the linker, including two WHEP domains, combined with structural analysis by small-angle neutron scattering, revealed a role for the WHEP domains in modulating conformations of the catalytic core and GSH- S -transferase-C-terminal-like (GST-C) domain. WHEP-driven conformational rearrangement altered GST-C domain interactions and conferred distinct oligomeric states in solution. Collectively, our results reveal long-range conformational changes imposed by the WHEP domains and illustrate how noncatalytic domains can modulate the global structure of tRNA synthetases in complex eukaryotic systems. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Genomic evidence for genes encoding leucine-rich repeat receptors linked to resistance against the eukaryotic extra- and intracellular Brassica napus pathogens Leptosphaeria maculans and Plasmodiophora brassicae.

PubMed

Stotz, Henrik U; Harvey, Pascoe J; Haddadi, Parham; Mashanova, Alla; Kukol, Andreas; Larkan, Nicholas J; Borhan, M Hossein; Fitt, Bruce D L

2018-01-01

Genes coding for nucleotide-binding leucine-rich repeat (LRR) receptors (NLRs) control resistance against intracellular (cell-penetrating) pathogens. However, evidence for a role of genes coding for proteins with LRR domains in resistance against extracellular (apoplastic) fungal pathogens is limited. Here, the distribution of genes coding for proteins with eLRR domains but lacking kinase domains was determined for the Brassica napus genome. Predictions of signal peptide and transmembrane regions divided these genes into 184 coding for receptor-like proteins (RLPs) and 121 coding for secreted proteins (SPs). Together with previously annotated NLRs, a total of 720 LRR genes were found. Leptosphaeria maculans-induced expression during a compatible interaction with cultivar Topas differed between RLP, SP and NLR gene families; NLR genes were induced relatively late, during the necrotrophic phase of pathogen colonization. Seven RLP, one SP and two NLR genes were found in Rlm1 and Rlm3/Rlm4/Rlm7/Rlm9 loci for resistance against L. maculans on chromosome A07 of B. napus. One NLR gene at the Rlm9 locus was positively selected, as was the RLP gene on chromosome A10 with LepR3 and Rlm2 alleles conferring resistance against L. maculans races with corresponding effectors AvrLm1 and AvrLm2, respectively. Known loci for resistance against L. maculans (extracellular hemi-biotrophic fungus), Sclerotinia sclerotiorum (necrotrophic fungus) and Plasmodiophora brassicae (intracellular, obligate biotrophic protist) were examined for presence of RLPs, SPs and NLRs in these regions. Whereas loci for resistance against P. brassicae were enriched for NLRs, no such signature was observed for the other pathogens. These findings demonstrate involvement of (i) NLR genes in resistance against the intracellular pathogen P. brassicae and a putative NLR gene in Rlm9-mediated resistance against the extracellular pathogen L. maculans.

User's manual for three dimensional FDTD version B code for scattering from frequency-dependent dielectric materials

NASA Technical Reports Server (NTRS)

Beggs, John H.; Luebbers, Raymond J.; Kunz, Karl S.

1992-01-01

The Penn State Finite Difference Time Domain Electromagnetic Code Version B is a three dimensional numerical electromagnetic scattering code based upon the Finite Difference Time Domain Technique (FDTD). The supplied version of the code is one version of our current three dimensional FDTD code set. This manual provides a description of the code and corresponding results for several scattering problems. The manual is organized into 14 sections: introduction, description of the FDTD method, operation, resource requirements, Version B code capabilities, a brief description of the default scattering geometry, a brief description of each subroutine, a description of the include file, a discussion of radar cross section computations, a discussion of some scattering results, a sample problem setup section, a new problem checklist, references and figure titles.

T cell specific adaptor protein (TSAd) promotes interaction of Nck with Lck and SLP-76 in T cells.

PubMed

Hem, Cecilie Dahl; Sundvold-Gjerstad, Vibeke; Granum, Stine; Koll, Lise; Abrahamsen, Greger; Buday, Laszlo; Spurkland, Anne

2015-07-11

The Lck and Src binding adaptor protein TSAd (T cell specific adaptor) regulates actin polymerization in T cells and endothelial cells. The molecular details as to how TSAd regulates this process remain to be elucidated. To identify novel interaction partners for TSAd, we used a scoring matrix-assisted ligand algorithm (SMALI), and found that the Src homology 2 (SH2) domain of the actin regulator Non-catalytic region of tyrosine kinase adaptor protein (Nck) potentially binds to TSAd phosphorylated on Tyr(280) (pTyr(280)) and pTyr(305). These predictions were confirmed by peptide array analysis, showing direct binding of recombinant Nck SH2 to both pTyr(280) and pTyr(305) on TSAd. In addition, the SH3 domains of Nck interacted with the proline rich region (PRR) of TSAd. Pull-down and immunoprecipitation experiments further confirmed the Nck-TSAd interactions through Nck SH2 and SH3 domains. In line with this Nck and TSAd co-localized in Jurkat cells as assessed by confocal microscopy and imaging flow cytometry. Co-immunoprecipitation experiments in Jurkat TAg cells lacking TSAd revealed that TSAd promotes interaction of Nck with Lck and SLP-76, but not Vav1. TSAd expressing Jurkat cells contained more polymerized actin, an effect dependent on TSAd exon 7, which includes interactions sites for both Nck and Lck. TSAd binds to and co-localizes with Nck. Expression of TSAd increases both Nck-Lck and Nck-SLP-76 interaction in T cells. Recruitment of Lck and SLP-76 to Nck by TSAd could be one mechanism by which TSAd promotes actin polymerization in activated T cells.

Group 12 Thiolates: Syntheses, Characterization and Decomposition Pathways

DTIC Science & Technology

1994-03-08

Stadard Form 298 (Rev 2-89) P ,e~cnwd by ANSI Std 1319. 1 94 3 1 1 180 92_1_ OFFICE OF NAVAL RESEARCH GRANT N00014-92-J-1820 R&T Code 4135035---01...Malik, M. Motevalli. P . O’Brian, Organometallics 10, 730 (1991). 3. M. Bochmann, K. J. Webb. M. Harman. M. B. Hursthouse, Angew. Chem. Int. Engl. Ed...29, 100 (1990). 4. M. Bochmann. K. J. Webb. M. B. Hursthouse, M. Mazid, J. Chem. Soc., Dalton Trans. 1991, 2317. 5. J. G. Brennan. T. Siegrist, P . J

Ligand-induced folding of the thiM TPP riboswitch investigated by a structure-based fluorescence spectroscopic approach

PubMed Central

Lang, Kathrin; Rieder, Renate; Micura, Ronald

2007-01-01

Riboswitches are genetic control elements within non-coding regions of mRNA. They consist of a metabolite-sensitive aptamer and an adjoining expression platform. Here, we describe ligand-induced folding of a thiamine pyrophosphate (TPP) responsive riboswitch from Escherichia coli thiM mRNA, using chemically labeled variants. Referring to a recent structure determination of the TPP/aptamer complex, each variant was synthesized with a single 2-aminopurine (AP) nucleobase replacement that was selected to monitor formation of tertiary interactions of a particular region during ligand binding in real time by fluorescence experiments. We have determined the rate constants for conformational adjustment of the individual AP sensors. From the 7-fold differentiation of these constants, it can be deduced that tertiary contacts between the two parallel helical domains (P2/J3-2/P3/L3 and P4/P5/L5) that grip the ligand's ends in two separate pockets, form significantly faster than the function-critical three-way junction with stem P1 fully developed. Based on these data, we characterize the process of ligand binding by an induced fit of the RNA and propose a folding model of the TPP riboswitch aptamer. For the full-length riboswitch domain and for shorter constructs that represent transcriptional intermediates, we have additionally evaluated ligand-induced folding via AP-modified variants and provide insights into the sequential folding pathway that involves a finely balanced equilibrium of secondary structures. PMID:17693433

Proceedings of the Portable Common Interface Set (PCIS) Workshop: Interface Technology Analyses (ITA2) (2nd) Held in Redondo Beach, California on 3-7 June 1991

DTIC Science & Technology

1991-10-01

Events (time) Constraints (conditions) States (context) Relationships among concepts Available requirements, design, code, and test Information 347 ...0fu 5) .2 75 - 04 P4 0 .)0 0 0 0 386 lima P38 r.0, t.. ~. Nowo C3 LUJ 0 6mBm L’J~ L..0)..... ’ LU I C070 N bau ~i389 ’I Ii uJJ I 390 0 0 z 0 z CLu SM...452-2117 EMAIL: Borowski, Bob NIST/PCISIIWCASE 2-a Protocol, A Division of Zycad 500 International Drive Mount Olive, NI 07828 PHONE: 201- 347 -7900

xRRM: a new class of RRM found in the telomerase La family protein p65.

PubMed

Singh, Mahavir; Choi, Charles P; Feigon, Juli

2013-03-01

Genuine La and La-related proteins group 7 (LARP7) bind to the non-coding RNAs transcribed by RNA polymerase III (RNAPIII), which end in UUU-3'OH. The La motif and RRM1 of these proteins (the La module) cooperate to bind the UUU-3'OH, protecting the RNA from degradation, while other domains may be important for RNA folding or other functions. Among the RNAPIII transcripts is ciliate telomerase RNA (TER). p65, a member of the LARP7 family, is an integral Tetrahymena thermophila telomerase holoenzyme protein required for TER biogenesis and telomerase RNP assembly. p65, together with TER and telomerase reverse transcriptase (TERT), form the Tetrahymena telomerase RNP catalytic core. p65 has an N-terminal domain followed by a La module and a C-terminal domain, which binds to the TER stem 4. We recently showed that the p65 C-terminal domain harbors a cryptic, atypical RRM, which uses a unique mode of single- and double-strand RNA binding and is required for telomerase RNP catalytic core assembly. This domain, which we named xRRM, appears to be present in and unique to genuine La and LARP7 proteins. Here we review the structure of the xRRM, discuss how this domain could recognize diverse substrates of La and LARP7 proteins and discuss the functional implications of the xRRM as an RNP chaperone.

Theoretical study of the gas-phase reactions of iodine atoms ((2)P(3/2)) with H(2), H(2)O, HI, and OH.

PubMed

Canneaux, Sébastien; Xerri, Bertrand; Louis, Florent; Cantrel, Laurent

2010-09-02

The rate constants of the reactions of iodine atoms with H(2), H(2)O, HI, and OH have been estimated using 39, 21, 13, and 39 different levels of theory, respectively, and have been compared to the available literature values over the temperature range of 250-2500 K. The aim of this methodological work is to demonstrate that standard theoretical methods are adequate to obtain quantitative rate constants for the reactions involving iodine-containing species. Geometry optimizations and vibrational frequency calculations are performed using three methods (MP2, MPW1K, and BHandHLYP) combined with three basis sets (cc-pVTZ, cc-pVQZ, and 6-311G(d,p)). Single-point energy calculations are performed with the highly correlated ab initio coupled cluster method in the space of single, double, and triple (pertubatively) electron excitations CCSD(T) using the cc-pVnZ (n = T, Q, and 5), aug-cc-pVnZ (n = T, Q, and 5), 6-311G(d,p), 6-311+G(3df,2p), and 6-311++G(3df,3pd) basis sets. Canonical transition state theory with a simple Wigner tunneling correction is used to predict the rate constants as a function of temperature. CCSD(T)/cc-pVnZ//MP2/cc-pVTZ (n = T and Q), CCSD(T)/6-311+G(3df,2p)//MP2/6-311G(d,p), and CCSD(T)/6-311++G(3df,3pd)//MP2/6-311G(d,p) levels of theory provide accurate kinetic rate constants when compared to available literature data. The use of the CCSD(T)/cc-pVQZ//MP2/cc-pVTZ and CCSD(T)/6-311++G(3df,3pd) levels of theory allows one to obtain a better agreement with the literature data for all reactions with the exception of the I + H(2) reaction R(1) . This computational procedure has been also used to predict rate constants for some reactions where no available experimental data exist. The use of quantum chemistry tools could be therefore extended to other elements and next applied to develop kinetic networks involving various fission products, steam, and hydrogen in the absence of literature data. The final objective is to implement the kinetics of gaseous reactions in the ASTEC (Accident Source Term Evaluation Code) code to improve speciation of fission transport, which can be transported along the Reactor Coolant System (RCS) of a Pressurized Water Reactor (PWR) in case of a severe accident.

New genetic variants of influenza A(H1N1)pdm09 detected in Cuba during 2011-2013.

PubMed

Arencibia, Amely; Acosta, Belsy; Muné, Mayra; Valdés, Odalys; Fernandez, Leandro; Medina, Isel; Savón, Clara; Oropesa, Suset; Gonzalez, Grehete; Roque, Rosmery; Gonzalez, Guelsys; Hernández, Bárbara; Goyenechea, Angel; Piñón, Alexander

2015-06-01

Influenza A(H1N1)pdm09 virus has evolved continually since its emergence in 2009. For influenza virus strains, genetic changes occurring in HA1 domain of the hemagglutinin cause the emergence of new variants. The aim of our study is to establish genetic associations between 35 A(H1N1)pdm09 viruses circulating in Cuba in 2011-2012 and 2012-2013 seasons, and A/California/07/2009 strain recommended by WHO as the H1N1 component of the influenza vaccine. The phylogenetic analysis revealed the circulation of clades 3, 6A, 6B, 6C and 7. Mutations were detected in the antigenic site or in the receptor-binding domains of HA1 segment, including S174P, S179N, K180Q, S202T, S220T and R222K. Substitutions S174P, S179N, K180Q and R222K were detected in Cuban strains for the first time. Copyright © 2015 Elsevier B.V. All rights reserved.

Numerical simulation of electromagnetic waves in Schwarzschild space-time by finite difference time domain method and Green function method

NASA Astrophysics Data System (ADS)

Jia, Shouqing; La, Dongsheng; Ma, Xuelian

2018-04-01

The finite difference time domain (FDTD) algorithm and Green function algorithm are implemented into the numerical simulation of electromagnetic waves in Schwarzschild space-time. FDTD method in curved space-time is developed by filling the flat space-time with an equivalent medium. Green function in curved space-time is obtained by solving transport equations. Simulation results validate both the FDTD code and Green function code. The methods developed in this paper offer a tool to solve electromagnetic scattering problems.

Novel domain-specific POU3F4 mutations are associated with X-linked deafness: examples from different populations.

PubMed

Bademci, Guney; Lasisi, Akeem; Yariz, Kemal O; Montenegro, Paola; Menendez, Ibis; Vinueza, Rodrigo; Paredes, Rosario; Moreta, Germania; Subasioglu, Asli; Blanton, Susan; Fitoz, Suat; Incesulu, Armagan; Sennaroglu, Levent; Tekin, Mustafa

2015-02-25

Mutations in the POU3F4 gene cause X-linked deafness type 3 (DFN3), which is characterized by inner ear anomalies. Three Turkish, one Ecuadorian, and one Nigerian families were included based on either inner ear anomalies detected in probands or X-linked family histories. Exome sequencing and/or Sanger sequencing were performed in order to identify the causative DNA variants in these families. Four novel, c.707A>C (p.(Glu236Ala)), c.772delG (p.(Glu258ArgfsX30)), c.902C>T (p.(Pro301Leu)), c.987T>C (p.(Ile308Thr)), and one previously reported mutation c.346delG (p.(Ala116ProfsX26)) in POU3F4, were identified. All mutations identified are predicted to affect the POU-specific or POU homeo domains of the protein and co-segregated with deafness in all families. Expanding the spectrum of POU3F4 mutations in different populations along with their associated phenotypes provides better understanding of their clinical importance and will be helpful in clinical evaluation and counseling of the affected individuals.

Toward rules relating zinc finger protein sequences and DNA binding site preferences.

PubMed

Desjarlais, J R; Berg, J M

1992-08-15

Zinc finger proteins of the Cys2-His2 type consist of tandem arrays of domains, where each domain appears to contact three adjacent base pairs of DNA through three key residues. We have designed and prepared a series of variants of the central zinc finger within the DNA binding domain of Sp1 by using information from an analysis of a large data base of zinc finger protein sequences. Through systematic variations at two of the three contact positions (underlined), relatively specific recognition of sequences of the form 5'-GGGGN(G or T)GGG-3' has been achieved. These results provide the basis for rules that may develop into a code that will allow the design of zinc finger proteins with preselected DNA site specificity.

VHSIC Hardware Description Language (VHDL) Benchmark Suite

DTIC Science & Technology

1990-10-01

T7 prit.iy label iTM Architecture label I flO inch Label I TIC ) P rae s Label I W Conkgurstion Spec. 1 21 Appendix B. Test Descriptions, Shell Code...Siensls R Accnss Operaist s Iov (soc 3 3 & 7 3 61 $ File I/0 S1 Reed S2 Write T Label Site TI Signal TIA Archi~ecture TIE Block TIC Port T2 VariableI...Access Operations I (sec 3 3 & 7.3 61 1 S FI I/0 1 Sl Read 52 Write T Label SreI TI Signal TIA Architeclt TIR Block TIC

Characterization of the Ruler Protein Interaction Interface on the Substrate Specificity Switch Protein in the Yersinia Type III Secretion System.

PubMed

Ho, Oanh; Rogne, Per; Edgren, Tomas; Wolf-Watz, Hans; Login, Frédéric H; Wolf-Watz, Magnus

2017-02-24

Many pathogenic Gram-negative bacteria use the type III secretion system (T3SS) to deliver effector proteins into eukaryotic host cells. In Yersinia , the switch to secretion of effector proteins is induced first after intimate contact between the bacterium and its eukaryotic target cell has been established, and the T3SS proteins YscP and YscU play a central role in this process. Here we identify the molecular details of the YscP binding site on YscU by means of nuclear magnetic resonance (NMR) spectroscopy. The binding interface is centered on the C-terminal domain of YscU. Disrupting the YscU-YscP interaction by introducing point mutations at the interaction interface significantly reduced the secretion of effector proteins and HeLa cell cytotoxicity. Interestingly, the binding of YscP to the slowly self-cleaving YscU variant P264A conferred significant protection against autoproteolysis. The YscP-mediated inhibition of YscU autoproteolysis suggests that the cleavage event may act as a timing switch in the regulation of early versus late T3SS substrates. We also show that YscU C binds to the inner rod protein YscI with a dissociation constant ( K d ) of 3.8 μm and with 1:1 stoichiometry. The significant similarity among different members of the YscU, YscP, and YscI families suggests that the protein-protein interactions discussed in this study are also relevant for other T3SS-containing Gram-negative bacteria. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Shock Spectrum Calculation from Acceleration Time Histories

DTIC Science & Technology

1980-09-01

CLASSIFICATIONe OF THIS PAGE (Uh-e DOg ~ 9--t)____________________ REPORT DOCUMENTATION PAGE BEFORE COMPLETING FORM I. REPRT NU9911ACCUIISIO6 NO .3ASCCSPICHT’S...SCE. Oakland CA NAVSCOLCECOFF C35 Port Hueneme. CA,. CO, Code C44A Porn Hueneme. CA NAVSEASYSCOM Code 05M13 (Newhouse) Wash DC; Code 6212, Wash DC

Reactive transport simulation via combination of a multiphase-capable transport code for unstructured meshes with a Gibbs energy minimization solver of geochemical equilibria

NASA Astrophysics Data System (ADS)

Fowler, S. J.; Driesner, T.; Hingerl, F. F.; Kulik, D. A.; Wagner, T.

2011-12-01

We apply a new, C++-based computational model for hydrothermal fluid-rock interaction and scale formation in geothermal reservoirs. The model couples the Complex System Modelling Platform (CSMP++) code for fluid flow in porous and fractured media (Matthai et al., 2007) with the Gibbs energy minimization numerical kernel GEMS3K of the GEM-Selektor (GEMS3) geochemical modelling package (Kulik et al., 2010) in a modular fashion. CSMP++ includes interfaces to commercial file formats, accommodating complex geometry construction using CAD (Rhinoceros) and meshing (ANSYS) software. The CSMP++ approach employs finite element-finite volume spatial discretization, implicit or explicit time discretization, and operator splitting. GEMS3K can calculate complex fluid-mineral equilibria based on a variety of equation of state and activity models. A selection of multi-electrolyte aqueous solution models, such as extended Debye-Huckel, Pitzer (Harvie et al., 1984), EUNIQUAC (Thomsen et al., 1996), and the new ELVIS model (Hingerl et al., this conference), makes it well-suited for application to a wide range of geothermal conditions. An advantage of the GEMS3K solver is simultaneous consideration of complex solid solutions (e.g., clay minerals), gases, fluids, and aqueous solutions. Each coupled simulation results in a thermodynamically-based description of the geochemical and physical state of a hydrothermal system evolving along a complex P-T-X path. The code design allows efficient, flexible incorporation of numerical and thermodynamic database improvements. We demonstrate the coupled code workflow and applicability to compositionally and physically complex natural systems relevant to enhanced geothermal systems, where temporally and spatially varying chemical interactions may take place within diverse lithologies of varying geometry. Engesgaard, P. & Kipp, K. L. (1992). Water Res. Res. 28: 2829-2843. Harvie, C. E.; Møller, N. & Weare, J. H. (1984). Geochim. Cosmochim. Acta 48: 723-751. Kulik, D. A., Wagner, T., Dmytrieva S. V, et al. (2010). GEM-Selektor home page, Paul Scherrer Institut. Available at http://gems.web.psi.ch. Matthäi, S. K., Geiger, S., Roberts, S. G., Paluszny, A., Belayneh, M., Burri, A., Mezentsev, A., Lu, H., Coumou, D., Driesner, T. & Heinrich C. A. (2007). Geol. Soc. London, Spec. Publ. 292: 405-429. Thomsen, K. Rasmussen, P. & Gani, R. (1996). Chem. Eng. Sci. 51: 3675-3683.

Colour cyclic code for Brillouin distributed sensors

NASA Astrophysics Data System (ADS)

Le Floch, Sébastien; Sauser, Florian; Llera, Miguel; Rochat, Etienne

2015-09-01

For the first time, a colour cyclic coding (CCC) is theoretically and experimentally demonstrated for Brillouin optical time-domain analysis (BOTDA) distributed sensors. Compared to traditional intensity-modulated cyclic codes, the code presents an additional gain of √2 while keeping the same number of sequences as for a colour coding. A comparison with a standard BOTDA sensor is realized and validates the theoretical coding gain.

p68 Sam is a substrate of the insulin receptor and associates with the SH2 domains of p85 PI3K.

PubMed

Sánchez-Margalet, V; Najib, S

1999-07-23

The 68 kDa Src substrate associated during mitosis is an RNA binding protein with Src homology 2 and 3 domain binding sites. A role for Src associated in mitosis 68 as an adaptor protein in signaling transduction has been proposed in different systems such as T-cell receptors. In the present work, we have sought to assess the possible role of Src associated in mitosis 68 in insulin receptor signaling. We performed in vivo studies in HTC-IR cells and in vitro studies using recombinant Src associated in mitosis 68, purified insulin receptor and fusion proteins containing either the N-terminal or the C-terminal Src homology 2 domain of p85 phosphatidylinositol-3-kinase. We have found that Src associated in mitosis 68 is a substrate of the insulin receptor both in vivo and in vitro. Moreover, tyrosine-phosphorylated Src associated in mitosis 68 was found to associate with p85 phosphatidylinositol-3-kinase in response to insulin, as assessed by co-immunoprecipitation studies. Therefore, Src associated in mitosis 68 may be part of the signaling complexes of insulin receptor along with p85. In vitro studies demonstrate that Src associated in mitosis 68 associates with the Src homology 2 domains of p85 after tyrosine phosphorylation by the activated insulin receptor. Moreover, tyr-phosphorylated Src associated in mitosis 68 binds with a higher affinity to the N-terminal Src homology 2 domain of p85 compared to the C-terminal Src homology 2 domain of p85, suggesting a preferential association of Src associated in mitosis 68 with the N-terminal Src homology 2 domain of p85. This association may be important for the link of the signaling with RNA metabolism.

Gene-Auto: Automatic Software Code Generation for Real-Time Embedded Systems

NASA Astrophysics Data System (ADS)

Rugina, A.-E.; Thomas, D.; Olive, X.; Veran, G.

2008-08-01

This paper gives an overview of the Gene-Auto ITEA European project, which aims at building a qualified C code generator from mathematical models under Matlab-Simulink and Scilab-Scicos. The project is driven by major European industry partners, active in the real-time embedded systems domains. The Gene- Auto code generator will significantly improve the current development processes in such domains by shortening the time to market and by guaranteeing the quality of the generated code through the use of formal methods. The first version of the Gene-Auto code generator has already been released and has gone thought a validation phase on real-life case studies defined by each project partner. The validation results are taken into account in the implementation of the second version of the code generator. The partners aim at introducing the Gene-Auto results into industrial development by 2010.

Finite difference time domain electromagnetic scattering from frequency-dependent lossy materials

NASA Technical Reports Server (NTRS)

Luebbers, Raymond J.; Beggs, John H.

1991-01-01

Four different FDTD computer codes and companion Radar Cross Section (RCS) conversion codes on magnetic media are submitted. A single three dimensional dispersive FDTD code for both dispersive dielectric and magnetic materials was developed, along with a user's manual. The extension of FDTD to more complicated materials was made. The code is efficient and is capable of modeling interesting radar targets using a modest computer workstation platform. RCS results for two different plate geometries are reported. The FDTD method was also extended to computing far zone time domain results in two dimensions. Also the capability to model nonlinear materials was incorporated into FDTD and validated.

Triton burnup in plasma focus plasmas

NASA Astrophysics Data System (ADS)

Brzosko, Jan S.; Brzosko, Jan R., Jr.; Robouch, Benjamin V.; Ingrosso, Luigi

1995-04-01

Pure deuterium plasma discharge from plasma focus breeds 1.01 MeV tritons via the D(d,p)T fusion branch, which has the same cross section as the D(d,n)3He (En=2.45 MeV) fusion branch. Tritons are trapped in and collide with the background deuterium plasma, producing 14.1 MeV neutrons via the D(t,n)4He reaction. The paper presents published in preliminary form as well as unpublished experimental data and theoretical studies of the neutron yield ratio R=Yn(14.1 MeV)/Yn(2.45 MeV). The experimental data were obtained from 1 MJ Frascati plasma focus operated at W=490 kJ with pure deuterium plasma (in the early 1980s). Neutrons were monitored using the nuclear activation method and nuclear emulsions. The present theoretical analysis of the experimental data is based on an exact adaptation of the binary encounter theory developed by Gryzinski. It is found that the experimentally defined value 1ṡ10-3

High rate of hypoglycemia in 6770 type 2 diabetes patients with comorbid dementia: A multicenter cohort study on 215,932 patients from the German/Austrian diabetes registry.

PubMed

Prinz, Nicole; Stingl, Julia; Dapp, Albrecht; Denkinger, Michael D; Fasching, Peter; Jehle, Peter M; Merger, Sigrun; Mühldorfer, Steffen; Pieper, Urte; Schuler, Andreas; Zeyfang, Andrej; Holl, Reinhard W

2016-02-01

Dementia and type 2 diabetes (T2D) are two major phenomena in older people. To compare anti-hyperglycemic therapy and diabetes-related comorbidities between elderly T2D patients with or without comorbid dementia. 215,932 type 2 diabetes patients aged ≥ 40 years (median [Q1;Q3]: 70.4 [61.2;77.7] years) from the standardized, multicenter German/Austrian diabetes patient registry, DPV, were studied. To identify patients with comorbid dementia, the registry was searched by ICD-10 codes, DSM-IV/-5 codes, respective search terms and/or disease-specific medication. For group comparisons, multiple hierarchic regression modeling with adjustments for age, sex, and duration of diabetes was applied. 3.1% (n=6770; 57% females) of the eligible T2D patients had clinically recognized comorbid dementia. After adjustment for demographics, severe hypoglycemia (insulin group: 14.8 ± 0.6 vs. 10.4 ± 0.2 events per 100 patient-years, p<0.001), hypoglycemia with coma (insulin group: 7.6 ± 0.4 vs. 3.9 ± 0.1 events per 100 patient-years, p<0.001), depression (9.9 vs. 4.7%, p<0.001), hypertension (74.7 vs. 72.2%, p<0.001), stroke (25.3 vs. 6.5%, p<0.001), diabetic foot syndrome (6.0 vs. 5.2%, p=0.004), and microalbuminuria (34.7 vs. 32.2%, p<0.001) were more common in dementia patients compared to T2D without dementia. Moreover, patients with dementia received insulin therapy more frequently (59.3 vs. 54.7%, p<0.001), but metabolic control (7.7 ± 0.1 vs. 7.7 ± 0.1%) was comparable to T2D without dementia. In T2D with dementia, higher rates of hypoglycemia and other diabetes-related comorbidities were observed. Hence, the risks of a glucocentric and intense diabetes management with insulin and a focus on tight glycemic control without considering other factors may outweigh the benefits in elderly T2D patients with comorbid dementia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Regulation of DNA replication timing on human chromosome by a cell-type specific DNA binding protein SATB1.

PubMed

Oda, Masako; Kanoh, Yutaka; Watanabe, Yoshihisa; Masai, Hisao

2012-01-01

Replication timing of metazoan DNA during S-phase may be determined by many factors including chromosome structures, nuclear positioning, patterns of histone modifications, and transcriptional activity. It may be determined by Mb-domain structures, termed as "replication domains", and recent findings indicate that replication timing is under developmental and cell type-specific regulation. We examined replication timing on the human 5q23/31 3.5-Mb segment in T cells and non-T cells. We used two independent methods to determine replication timing. One is quantification of nascent replicating DNA in cell cycle-fractionated stage-specific S phase populations. The other is FISH analyses of replication foci. Although the locations of early- and late-replicating domains were common between the two cell lines, the timing transition region (TTR) between early and late domains were offset by 200-kb. We show that Special AT-rich sequence Binding protein 1 (SATB1), specifically expressed in T-cells, binds to the early domain immediately adjacent to TTR and delays the replication timing of the TTR. Measurement of the chromosome copy number along the TTR during synchronized S phase suggests that the fork movement may be slowed down by SATB1. Our results reveal a novel role of SATB1 in cell type-specific regulation of replication timing along the chromosome.

What provides a better value for your time? The use of relative value units to compare posterior segmental instrumentation of vertebral segments.

PubMed

Orr, R Douglas; Sodhi, Nipun; Dalton, Sarah E; Khlopas, Anton; Sultan, Assem A; Chughtai, Morad; Newman, Jared M; Savage, Jason; Mroz, Thomas E; Mont, Michael A

2018-02-02

Relative value units (RVUs) are a compensation model based on the effort required to provide a procedure or service to a patient. Thus, procedures that are more complex and require greater technical skill and aftercare, such as multilevel spine surgery, should provide greater physician compensation. However, there are limited data comparing RVUs with operative time. Therefore, this study aims to compare mean (1) operative times; (2) RVUs; and (3) RVU/min between posterior segmental instrumentation of 3-6, 7-12, and ≥13 vertebral segments, and to perform annual cost difference analysis. A total of 437 patients who underwent instrumentation of 3-6 segments (Cohort 1, current procedural terminology [CPT] code: 22842), 67 patients who had instrumentation of 7-12 segments (Cohort 2, CPT code: 22843), and 16 patients who had instrumentation of ≥13 segments (Cohort 3, CPT code: 22844) were identified from the National Surgical Quality Improvement Program (NSQIP) database. Mean operative times, RVUs, and RVU/min, as well as an annualized cost difference analysis, were calculated and compared using Student t test. This study received no funding from any party or entity. Cohort 1 had shorter mean operative times than Cohorts 2 and 3 (217 minutes vs. 325 minutes vs. 426 minutes, p<.05). Cohort 1 had a lower mean RVU than Cohorts 2 and 3 (12.6 vs. 13.4 vs. 16.4). Cohort 1 had a greater RVU/min than Cohorts 2 and 3 (0.08 vs. 0.05, p<.05; vs. 0.08 vs. 0.05, p>.05). A $112,432.12 annualized cost difference between Cohorts 1 and 2, a $176,744.76 difference between Cohorts 1 and 3, and a $64,312.55 difference between Cohorts 2 and 3 were calculated. The RVU/min takes into account not just the value provided but also the operative times required for highly complex cases. The RVU/min for fewer vertebral level instrumentation being greater (0.08 vs. 0.05), as well as the $177,000 annualized cost difference, indicates that compensation is not proportional to the added time, effort, and skill for more complex cases. Copyright © 2018 Elsevier Inc. All rights reserved.

Evidence that the tandem-pleckstrin-homology-domain-containing protein TAPP1 interacts with Ptd(3,4)P2 and the multi-PDZ-domain-containing protein MUPP1 in vivo.

PubMed Central

Kimber, Wendy A; Trinkle-Mulcahy, Laura; Cheung, Peter C F; Deak, Maria; Marsden, Louisa J; Kieloch, Agnieszka; Watt, Stephen; Javier, Ronald T; Gray, Alex; Downes, C Peter; Lucocq, John M; Alessi, Dario R

2002-01-01

PtdIns(3,4,5)P3 is an established second messenger of growth-factor and insulin-induced signalling pathways. There is increasing evidence that one of the immediate breakdown products of PtdIns(3,4,5)P3, namely PtdIns(3,4)P2, whose levels are elevated by numerous extracellular agonists, might also function as a signalling molecule. Recently, we identified two related pleckstrin-homology (PH)-domain-containing proteins, termed 'tandem-PH-domain-containing protein-1' (TAPP1) and TAPP2, which interacted in vitro with high affinity with PtdIns(3,4)P2, but did not bind PtdIns(3,4,5)P3 or other phosphoinositides. In the present study we demonstrate that stimulation of Swiss 3T3 or 293 cells with agonists that stimulate PtdIns(3,4)P2 production results in the marked translocation of TAPP1 to the plasma membrane. This recruitment is dependent on a functional PtdIns(3,4)P2-binding PH domain and is inhibited by wortmannin, a phosphoinositide 3-kinase inhibitor that prevents PtdIns(3,4)P2 generation. A search for proteins that interact with TAPP1 identified the multi-PDZ-containing protein termed 'MUPP1', a protein possessing 13 PDZ domains and no other known modular or catalytic domains [PDZ is postsynaptic density protein (PSD-95)/Drosophila disc large tumour suppressor (dlg)/tight junction protein (ZO1)]. We demonstrate that immunoprecipitation of endogenously expressed TAPP1 from 293-cell lysates results in the co-immunoprecipitation of endogenous MUPP1, indicating that these proteins are likely to interact with each other physiologically. We show that TAPP1 and TAPP2 interact with the 10th and 13th PDZ domain of MUPP1 through their C-terminal amino acids. The results of the present study suggest that TAPP1 and TAPP2 could function in cells as adapter proteins to recruit MUPP1, or other proteins that they may interact with, to the plasma membrane in response to signals that elevate PtdIns(3,4)P2. PMID:11802782

User's manual for two dimensional FDTD version TEA and TMA codes for scattering from frequency-independent dielectic materials

NASA Technical Reports Server (NTRS)

Beggs, John H.; Luebbers, Raymond J.; Kunz, Karl S.

1991-01-01

The Penn State Finite Difference Time Domain Electromagnetic Scattering Code Versions TEA and TMA are two dimensional numerical electromagnetic scattering codes based upon the Finite Difference Time Domain Technique (FDTD) first proposed by Yee in 1966. The supplied version of the codes are two versions of our current two dimensional FDTD code set. This manual provides a description of the codes and corresponding results for the default scattering problem. The manual is organized into eleven sections: introduction, Version TEA and TMA code capabilities, a brief description of the default scattering geometry, a brief description of each subroutine, a description of the include files (TEACOM.FOR TMACOM.FOR), a section briefly discussing scattering width computations, a section discussing the scattering results, a sample problem set section, a new problem checklist, references and figure titles.

User's manual for two dimensional FDTD version TEA and TMA codes for scattering from frequency-independent dielectric materials

NASA Technical Reports Server (NTRS)

Beggs, John H.; Luebbers, Raymond J.; Kunz, Karl S.

1991-01-01

The Penn State Finite Difference Time Domain Electromagnetic Scattering Code Versions TEA and TMA are two dimensional electromagnetic scattering codes based on the Finite Difference Time Domain Technique (FDTD) first proposed by Yee in 1966. The supplied version of the codes are two versions of our current FDTD code set. This manual provides a description of the codes and corresponding results for the default scattering problem. The manual is organized into eleven sections: introduction, Version TEA and TMA code capabilities, a brief description of the default scattering geometry, a brief description of each subroutine, a description of the include files (TEACOM.FOR TMACOM.FOR), a section briefly discussing scattering width computations, a section discussing the scattering results, a sample problem setup section, a new problem checklist, references, and figure titles.

User's manual for three dimensional FDTD version C code for scattering from frequency-independent dielectric and magnetic materials

NASA Technical Reports Server (NTRS)

Beggs, John H.; Luebbers, Raymond J.; Kunz, Karl S.

1991-01-01

The Penn State Finite Difference Time Domain Electromagnetic Scattering Code Version C is a three dimensional numerical electromagnetic scattering code based upon the Finite Difference Time Domain Technique (FDTD). The supplied version of the code is one version of our current three dimensional FDTD code set. This manual provides a description of the code and corresponding results for several scattering problems. The manual is organized into fourteen sections: introduction, description of the FDTD method, operation, resource requirements, Version C code capabilities, a brief description of the default scattering geometry, a brief description of each subroutine, a description of the include file (COMMONC.FOR), a section briefly discussing Radar Cross Section (RCS) computations, a section discussing some scattering results, a sample problem setup section, a new problem checklist, references and figure titles.

User's manual for three dimensional FDTD version D code for scattering from frequency-dependent dielectric and magnetic materials

NASA Technical Reports Server (NTRS)

Beggs, John H.; Luebbers, Raymond J.; Kunz, Karl S.

1991-01-01

The Penn State Finite Difference Time Domain Electromagnetic Scattering Code Version D is a three dimensional numerical electromagnetic scattering code based upon the Finite Difference Time Domain Technique (FDTD). The supplied version of the code is one version of our current three dimensional FDTD code set. This manual provides a description of the code and corresponding results for several scattering problems. The manual is organized into fourteen sections: introduction, description of the FDTD method, operation, resource requirements, Version D code capabilities, a brief description of the default scattering geometry, a brief description of each subroutine, a description of the include file (COMMOND.FOR), a section briefly discussing Radar Cross Section (RCS) computations, a section discussing some scattering results, a sample problem setup section, a new problem checklist, references and figure titles.

User's manual for three dimensional FDTD version A code for scattering from frequency-independent dielectric materials

NASA Technical Reports Server (NTRS)

Beggs, John H.; Luebbers, Raymond J.; Kunz, Karl S.

1992-01-01

The Penn State Finite Difference Time Domain (FDTD) Electromagnetic Scattering Code Version A is a three dimensional numerical electromagnetic scattering code based on the Finite Difference Time Domain technique. The supplied version of the code is one version of our current three dimensional FDTD code set. The manual provides a description of the code and the corresponding results for the default scattering problem. The manual is organized into 14 sections: introduction, description of the FDTD method, operation, resource requirements, Version A code capabilities, a brief description of the default scattering geometry, a brief description of each subroutine, a description of the include file (COMMONA.FOR), a section briefly discussing radar cross section (RCS) computations, a section discussing the scattering results, a sample problem setup section, a new problem checklist, references, and figure titles.

User's manual for three dimensional FDTD version C code for scattering from frequency-independent dielectric and magnetic materials

NASA Technical Reports Server (NTRS)

Beggs, John H.; Luebbers, Raymond J.; Kunz, Karl S.

1992-01-01

The Penn State Finite Difference Time Domain Electromagnetic Scattering Code Version C is a three-dimensional numerical electromagnetic scattering code based on the Finite Difference Time Domain (FDTD) technique. The supplied version of the code is one version of our current three-dimensional FDTD code set. The manual given here provides a description of the code and corresponding results for several scattering problems. The manual is organized into 14 sections: introduction, description of the FDTD method, operation, resource requirements, Version C code capabilities, a brief description of the default scattering geometry, a brief description of each subroutine, a description of the include file (COMMONC.FOR), a section briefly discussing radar cross section computations, a section discussing some scattering results, a new problem checklist, references, and figure titles.

User's manual for three dimensional FDTD version B code for scattering from frequency-dependent dielectric materials

NASA Technical Reports Server (NTRS)

Beggs, John H.; Luebbers, Raymond J.; Kunz, Karl S.

1991-01-01

The Penn State Finite Difference Time Domain Electromagnetic Scattering Code Version B is a three dimensional numerical electromagnetic scattering code based upon the Finite Difference Time Domain Technique (FDTD). The supplied version of the code is one version of our current three dimensional FDTD code set. This manual provides a description of the code and corresponding results for several scattering problems. The manual is organized into fourteen sections: introduction, description of the FDTD method, operation, resource requirements, Version B code capabilities, a brief description of the default scattering geometry, a brief description of each subroutine, a description of the include file (COMMONB.FOR), a section briefly discussing Radar Cross Section (RCS) computations, a section discussing some scattering results, a sample problem setup section, a new problem checklist, references and figure titles.

Proceedings of the Spacecraft Charging Technology Conference Held in Monterey, California on 31 October - 3 November 1989. Volume 2

DTIC Science & Technology

1989-11-01

STATEMENT 12b. DISTRIBUTION CODE Approved for public release; distribution unlimited 13. ABSTRACT (Maximum 200 words) The Spacecraft Charging... Distribution I D Availability Codes ’ Avail and/orDist Special VIvt PREFACE The Spacecraft Charging Technology conference was held at the Naval... distribution , the spacecraft will charge negatively during this time according to dV/dt = 47ta 2 Jth ev/° / C whose solution is V/0= - ln(l + t/t) "t = C 0

Characterising the slope of the distance-time relationship in swimming.

PubMed

Dekerle, J; Brickley, G; Alberty, M; Pelayo, P

2010-05-01

The aim of the present study was to assess whether the critical speed calculated by the slope of the distance-time relationship (S(d-t)) represents the boundary between the heavy and severe intensity domains in swimming and would be sustainable during intermittent exercise. Nine competitive male swimmers (mean+/-SD: aged 21.2+/-2.6 yrs; peak (.)VO2 of 3866+/-529 mL min(-1)) performed, (a) four fixed-distance (100-200-400-800 m) all-out efforts to determine S(d-t) and peak (.)VO2; (b) three constant-speed efforts to exhaustion (TTE) at and 5% above and below S(d-t) (S(d-t)(+5%) and S(d-t)(-5%), respectively); (c) a set of 10 x 400 m at S(d-t) with 40-s recovery in between. Capillary blood lactate concentration ([La](B)), oxygen uptake ((.)VO2), and RPE remained stable at S(d-t)(-5%) (TTE=48.9+/-14.1 min) with end values of 3.8+/-1.9 mmol L(-1), 87+/-14% peak (.)VO2, and 4.7+/-1.3. TTE decreased at S(d-t)(+5%) (8.6+/-3.1 min), with end [La](B) of 10.2+/-1.9 mmol L(-1). Peak (.)VO2 was reached at exhaustion. Similarly, S(d-t) could only be maintained for 24.3+/-7.7 min with an increase in RPE and [La](B), (.)VO2 reaching its peak (95+/-5% peak VO2). RPE increased but [La](B) remained stable throughout the ten 400 m blocks performed at S(d-t) (overall time of 53.9+/-2.7 min). The physiological responses when swimming 5% below and 5% above S(d-t) are those characterising the heavy and severe intensity domain, respectively. While S(d-t) lies within the severe intensity domain, intermittent swims at this intensity induce [La](B) steady state alongside high rates of perceived exertion. 2009 Sports Medicine Australia. All rights reserved.

Los1p, involved in yeast pre-tRNA splicing, positively regulates members of the SOL gene family

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

Shen, W.C.; Stanford, D.R.; Hopper, A.K.

1996-06-01

To understand the role of Los1p in pre-tRNA splicing, we sought los1 multicopy suppressors. We found SOL1 that suppresses both point and null LOS1 mutations. Since, when fused to the Gal4p DNA-binding domain, Los1p activates transcription, we tested whether Los1p regulates SOL1. We found that los1 mutants have depleted levels of SOL1 mRNA and Sol1p. Thus, LOS1 appears to positively regulate SOL1. SOL1 belongs to a multigene family with at least two additional members, SOL2 and SOL3. Sol proteins have extensive similarity to an unusual group of glucose-6-phosphate dehydrogenases (G6PDs). As the similarities are restricted to areas separate from themore » catalytic domain, these G6PDs may have more than one function. The SOL gene disruptions negatively affect tRNA-mediated nonsense suppression and the severity increases with the number of mutant SOL genes. However, tRNA levels do not vary with either multicopy SOL genes or with SOL disruptions. Therefore, the Sol proteins affect tRNA expression/function at steps other than transcription or splicing. We propose that LOS1 regulates gene products involved in tRNA expression/function as well as pre-tRNA splicing. 64 refs., 6 figs., 6 tabs.« less

TIM-1 glycoprotein binds the adhesion receptor P-selectin and mediates T cell trafficking during inflammation and autoimmunity

PubMed Central

Angiari, Stefano; Donnarumma, Tiziano; Rossi, Barbara; Dusi, Silvia; Pietronigro, Enrica; Zenaro, Elena; Della Bianca, Vittorina; Toffali, Lara; Piacentino, Gennj; Budui, Simona; Rennert, Paul; Xiao, Sheng; Laudanna, Carlo; Casasnovas, Jose M.; Kuchroo, Vijay K.; Constantin, Gabriela

2014-01-01

SUMMARY Selectins play a central role in leukocyte trafficking by mediating tethering and rolling on vascular surfaces. Here we have reported that T cell immunoglobulin and mucin domain 1 (TIM-1) is a P-selectin ligand. We have shown that human and murine TIM-1 binds to P-selectin, and that TIM-1 mediates tethering and rolling of T helper-1 (Th1) and Th17, but not Th2 and regulatory T cells on P-selectin. Th1 and Th17 cells lacking the TIM-1 mucin domain showed reduced rolling in thrombin-activated mesenteric venules and inflamed brain microcirculation. Inhibition of TIM-1 had no effect on naive T cell homing, but reduced T cell recruitment in a skin hypersensitivity model and blocked experimental autoimmune encephalomyelitis. Uniquely, the TIM-1 IgV domain was also required for P-selectin binding. Our data demonstrate that TIM-1 is a major P-selectin ligand with a specialized role in T cell trafficking during inflammatory responses and the induction of autoimmune disease. PMID:24703780

Cooperative and selective roles of the WW domains of the yeast Nedd4-like ubiquitin ligase Rsp5 in the recognition of the arrestin-like adaptors Bul1 and Bul2.

PubMed

Watanabe, Daisuke; Murai, Hiroki; Tanahashi, Ryoya; Nakamura, Keishi; Sasaki, Toshiya; Takagi, Hiroshi

The ubiquitin ligase Rsp5, which is the only yeast Saccharomyces cerevisiae member of the Nedd4-family, recognizes and ubiquitinates various substrate proteins through the functions of three conserved WW domains. To elucidate the role of each WW domain in endocytosis of the general amino acid permease Gap1 via interaction with the arrestin-like adaptor proteins Bul1 and Bul2 (Bul1/2), we investigated the effects of the double mutations that abrogate the recognition of PY motifs on target proteins (rsp5(W257F/P260A), rsp5(W359F/P362A), and rsp5(W415F/P418A)) and the alanine substitutions of the conserved threonine residues that are regarded as putative phosphorylation sites (rsp5(T255A), RSP5(T357A), and rsp5(T413A)), both of which are located within each WW domain. The rsp5(W257F/P260A), rsp5(W359F/P362A), and rsp5(W415F/P418A) mutations increased sensitivity to the proline analog azetidine-2-carboxylate (AZC), defective endocytosis of Gap1, and impaired interactions with Bul1. These results demonstrate that molecular recognition by each WW domain is responsible for the cooperative interaction with Bul1. Intriguingly, the RSP5(T357A) mutation enhanced AZC tolerance and endocytosis of Gap1, although rsp5(T255A) and rsp5(T413A) decreased both of them. While rsp5(T255A), RSP5(T357A), and rsp5(T413A) impaired the interaction of Rsp5 with Bul1, the RSP5(T357A) mutation specifically augmented the interaction with Bul2. The AZC tolerance enhanced by RSP5(T357A) was fully abolished by combining with each of the rsp5(W257F/P260A), rsp5(W359F/P362A), or rsp5(W415F/P418A) mutations. It was thus suggested that Thr357 in the WW2 domain has a unique role in preventing from the constitutive activation of Bul1/2-mediated endocytosis of Gap1. Taken together, our results highlight the cooperative and specific roles of WW domains in the regulation of Bul1/2-mediated cellular events. Copyright © 2015 Elsevier Inc. All rights reserved.

Sequence and expression analyses of porcine ISG15 and ISG43 genes.

PubMed

Huang, Jiangnan; Zhao, Shuhong; Zhu, Mengjin; Wu, Zhenfang; Yu, Mei

2009-08-01

The coding sequences of porcine interferon-stimulated gene 15 (ISG15) and the interferon-stimulated gene (ISG43) were cloned from swine spleen mRNA. The amino acid sequences deduced from porcine ISG15 and ISG43 genes coding sequence shared 24-75% and 29-83% similarity with ISG15s and ISG43s from other vertebrates, respectively. Structural analyses revealed that porcine ISG15 comprises two ubiquitin homologues motifs (UBQ) domain and a conserved C-terminal LRLRGG conjugating motif. Porcine ISG43 contains an ubiquitin-processing proteases-like domain. Phylogenetic analyses showed that porcine ISG15 and ISG43 were mostly related to rat ISG15 and cattle ISG43, respectively. Using quantitative real-time PCR assay, significant increased expression levels of porcine ISG15 and ISG43 genes were detected in porcine kidney endothelial cells (PK15) cells treated with poly I:C. We also observed the enhanced mRNA expression of three members of dsRNA pattern-recognition receptors (PRR), TLR3, DDX58 and IFIH1, which have been reported to act as critical receptors in inducing the mRNA expression of ISG15 and ISG43 genes. However, we did not detect any induced mRNA expression of IFNalpha and IFNbeta, suggesting that transcriptional activations of ISG15 and ISG43 were mediated through IFN-independent signaling pathway in the poly I:C treated PK15 cells. Association analyses in a Landrace pig population revealed that ISG15 c.347T>C (BstUI) polymorphism and the ISG43 c.953T>G (BccI) polymorphism were significantly associated with hematological parameters and immune-related traits.

A New Supramolecular Route for Using Rod-Coil Block Copolymers in Photovoltaic Applications

NASA Astrophysics Data System (ADS)

Mezzenga, Raffaele; Sary, Nicolas; Richard, Fanny; Brochon, Cyril; Leclerc, Nicolas; Leveque, Patrick; Audinot, Jean Nicolas; Heiser, Thomas; Hadziioannou, Georges; Berson, Solenn

2010-03-01

We propose a new supramolecular strategy to blend together rod-coil poly(3-hexylthiophene)-poly(4-vinylpyridine) (P3HTP4VP) block copolymers and [6,6]-phenyl-C61-butyric acid methyl ester (PCBM). The P4VP and PCBM are mixed together by weak supramolecular interactions, and the resulting materials exhibit microphase separated morphologies of electron-donor and electron-acceptor rich domains. The microphase segregated P3HT-rod domains act as electron-donating species and the homogeneous P4VP block:PCBM blend acts as the electron-acceptor domain. We describe the photovoltaic performance of standard and inverted devices whose active layer is composed thereof and show the effect of finely engineering the interfacial properties of the active layer to obtain competitive photovoltaic performance with superior thermal stability. (1) N. Sary, F. Richard, C. Brochon, N. Leclerc, P. Leveque, JN Audinot, S. Berson, T. Heiser, G. Hadziioannou, R. Mezzenga, Adv. Mater. in Press (2010)

Validation of a Monte Carlo code system for grid evaluation with interference effect on Rayleigh scattering

NASA Astrophysics Data System (ADS)

Zhou, Abel; White, Graeme L.; Davidson, Rob

2018-02-01

Anti-scatter grids are commonly used in x-ray imaging systems to reduce scatter radiation reaching the image receptor. Anti-scatter grid performance and validation can be simulated through use of Monte Carlo (MC) methods. Our recently reported work has modified existing MC codes resulting in improved performance when simulating x-ray imaging. The aim of this work is to validate the transmission of x-ray photons in grids from the recently reported new MC codes against experimental results and results previously reported in other literature. The results of this work show that the scatter-to-primary ratio (SPR), the transmissions of primary (T p), scatter (T s), and total (T t) radiation determined using this new MC code system have strong agreement with the experimental results and the results reported in the literature. T p, T s, T t, and SPR determined in this new MC simulation code system are valid. These results also show that the interference effect on Rayleigh scattering should not be neglected in both mammographic and general grids’ evaluation. Our new MC simulation code system has been shown to be valid and can be used for analysing and evaluating the designs of grids.

Characterization of the DMAE-modified juvenile excretory-secretory protein Juv-p120 of Litomosoides sigmodontis.

PubMed

Wagner, Ulrike; Hirzmann, Jörg; Hintz, Martin; Beck, Ewald; Geyer, Rudolf; Hobom, Gerd; Taubert, Anja; Zahner, Horst

2011-04-01

Juv-p120 is an excretory-secretory 160 kDa glycoprotein of juvenile female Litomosoides sigmodontis and exhibits features typical for mucins. 50% of its molecular mass is attributed to posttranslational modifications with the unusual substituent dimethylaminoethanol (DMAE). By that Juv-p120 corresponds to the surface proteins of the microfilarial sheath, Shp3 and Shp3a. The secreted protein consists of 697 amino acids, organized in two different domains of repeat elements separated by a stretch of polar residues. The N-terminal domain shows fourteen P/S/T/F-rich repeat elements highly modified with phospho-DMAE substituted O-glycans confering a negative charge to the protein. The C-terminal domain is extremely rich in glutamine (35%) and leucine (25%) in less organized repeats and may play a role in oligomerization of Juv-p120 monomers. A protein family with a similar Q/L-rich region and conserved core promoter region was identified in Brugia malayi by homology screening and in Wuchereria bancrofti and Loa loa by database similarity search. One of the Q/L-rich proteins in each genus has an extended S/T-rich region and due to this feature is supposed to be a putative Juv-p120 ortholog. The corresponding modification of Juv-p120 and the microfilarial sheath surface antigens Shp3/3a explains the appearance of anti-sheath antibodies before the release of microfilariae. The function of Juv-p120 is unknown. Copyright © 2011 Elsevier B.V. All rights reserved.

3D-radiative transfer in terrestrial atmosphere: An efficient parallel numerical procedure

NASA Astrophysics Data System (ADS)

Bass, L. P.; Germogenova, T. A.; Nikolaeva, O. V.; Kokhanovsky, A. A.; Kuznetsov, V. S.

2003-04-01

Light propagation and scattering in terrestrial atmosphere is usually studied in the framework of the 1D radiative transfer theory [1]. However, in reality particles (e.g., ice crystals, solid and liquid aerosols, cloud droplets) are randomly distributed in 3D space. In particular, their concentrations vary both in vertical and horizontal directions. Therefore, 3D effects influence modern cloud and aerosol retrieval procedures, which are currently based on the 1D radiative transfer theory. It should be pointed out that the standard radiative transfer equation allows to study these more complex situations as well [2]. In recent year the parallel version of the 2D and 3D RADUGA code has been developed. This version is successfully used in gammas and neutrons transport problems [3]. Applications of this code to radiative transfer in atmosphere problems are contained in [4]. Possibilities of code RADUGA are presented in [5]. The RADUGA code system is an universal solver of radiative transfer problems for complicated models, including 2D and 3D aerosol and cloud fields with arbitrary scattering anisotropy, light absorption, inhomogeneous underlying surface and topography. Both delta type and distributed light sources can be accounted for in the framework of the algorithm developed. The accurate numerical procedure is based on the new discrete ordinate SWDD scheme [6]. The algorithm is specifically designed for parallel supercomputers. The version RADUGA 5.1(P) can run on MBC1000M [7] (768 processors with 10 Gb of hard disc memory for each processor). The peak productivity is equal 1 Tfl. Corresponding scalar version RADUGA 5.1 is working on PC. As a first example of application of the algorithm developed, we have studied the shadowing effects of clouds on neighboring cloudless atmosphere, depending on the cloud optical thickness, surface albedo, and illumination conditions. This is of importance for modern satellite aerosol retrieval algorithms development. [1] Sobolev, V. V., 1972: Light scattering in planetary atmosphere, M.:Nauka. [2] Evans, K. F., 1998: The spherical harmonic discrete ordinate method for three dimensional atmospheric radiative transfer, J. Atmos. Sci., 55, 429 446. [3] L.P. Bass, T.A. Germogenova, V.S. Kuznetsov, O.V. Nikolaeva. RADUGA 5.1 and RADUGA 5.1(P) codes for stationary transport equation solution in 2D and 3D geometries on one and multiprocessors computers. Report on seminar “Algorithms and Codes for neutron physical of nuclear reactor calculations” (Neutronica 2001), Obninsk, Russia, 30 October 2 November 2001. [4] T.A. Germogenova, L.P. Bass, V.S. Kuznetsov, O.V. Nikolaeva. Mathematical modeling on parallel computers solar and laser radiation transport in 3D atmosphere. Report on International Symposium CIS countries “Atmosphere radiation”, 18 21 June 2002, St. Peterburg, Russia, p. 15 16. [5] L.P. Bass, T.A. Germogenova, O.V. Nikolaeva, V.S. Kuznetsov. Radiative Transfer Universal 2D 3D Code RADUGA 5.1(P) for Multiprocessor Computer. Abstract. Poster report on this Meeting. [6] L.P. Bass, O.V. Nikolaeva. Correct calculation of Angular Flux Distribution in Strongly Heterogeneous Media and Voids. Proc. of Joint International Conference on Mathematical Methods and Supercomputing for Nuclear Applications, Saratoga Springs, New York, October 5 9, 1997, p. 995 1004. [7] http://www/jscc.ru

Simplified Two-Time Step Method for Calculating Combustion and Emission Rates of Jet-A and Methane Fuel With and Without Water Injection

NASA Technical Reports Server (NTRS)

Molnar, Melissa; Marek, C. John

2005-01-01

A simplified kinetic scheme for Jet-A, and methane fuels with water injection was developed to be used in numerical combustion codes, such as the National Combustor Code (NCC) or even simple FORTRAN codes. The two time step method is either an initial time averaged value (step one) or an instantaneous value (step two). The switch is based on the water concentration in moles/cc of 1x10(exp -20). The results presented here results in a correlation that gives the chemical kinetic time as two separate functions. This two time step method is used as opposed to a one step time averaged method previously developed to determine the chemical kinetic time with increased accuracy. The first time averaged step is used at the initial times for smaller water concentrations. This gives the average chemical kinetic time as a function of initial overall fuel air ratio, initial water to fuel mass ratio, temperature, and pressure. The second instantaneous step, to be used with higher water concentrations, gives the chemical kinetic time as a function of instantaneous fuel and water mole concentration, pressure and temperature (T4). The simple correlations would then be compared to the turbulent mixing times to determine the limiting rates of the reaction. The NASA Glenn GLSENS kinetics code calculates the reaction rates and rate constants for each species in a kinetic scheme for finite kinetic rates. These reaction rates are used to calculate the necessary chemical kinetic times. Chemical kinetic time equations for fuel, carbon monoxide and NOx are obtained for Jet-A fuel and methane with and without water injection to water mass loadings of 2/1 water to fuel. A similar correlation was also developed using data from NASA's Chemical Equilibrium Applications (CEA) code to determine the equilibrium concentrations of carbon monoxide and nitrogen oxide as functions of overall equivalence ratio, water to fuel mass ratio, pressure and temperature (T3). The temperature of the gas entering the turbine (T4) was also correlated as a function of the initial combustor temperature (T3), equivalence ratio, water to fuel mass ratio, and pressure.

Translocation of the Catalytic Domain of Diphtheria Toxin across Planar Phospholipid Bilayers by Its Own T Domain

NASA Astrophysics Data System (ADS)

Oh, Kyoung Joon; Senzel, Lisa; Collier, R. John; Finkelstein, Alan

1999-07-01

The T domain of diphtheria toxin is known to participate in the pH-dependent translocation of the catalytic C domain of the toxin across the endosomal membrane, but how it does so, and whether cellular proteins are also required for this process, remain unknown. Here, we report results showing that the T domain alone is capable of translocating the entire C domain across model, planar phospholipid bilayers in the absence of other proteins. The T domain therefore contains the entire molecular machinery for mediating transfer of the catalytic domain of diphtheria toxin across membranes.

Draft Genome Sequence of Pseudomonas oceani DSM 100277T, a Deep-Sea Bacterium

PubMed Central

2018-01-01

ABSTRACT Pseudomonas oceani DSM 100277T was isolated from deep seawater in the Okinawa Trough at 1390 m. P. oceani belongs to the Pseudomonas pertucinogena group. Here, we report the draft genome sequence of P. oceani, which has an estimated size of 4.1 Mb and exhibits 3,790 coding sequences, with a G+C content of 59.94 mol%. PMID:29650573

Species-Specific Elements in the Large T-Antigen J Domain Are Required for Cellular Transformation and DNA Replication by Simian Virus 40

PubMed Central

Sullivan, Christopher S.; Tremblay, James D.; Fewell, Sheara W.; Lewis, John A.; Brodsky, Jeffrey L.; Pipas, James M.

2000-01-01

The J domain of simian virus 40 (SV40) large T antigen is required for efficient DNA replication and transformation. Despite previous reports demonstrating the promiscuity of J domains in heterologous systems, results presented here show the requirement for specific J-domain sequences in SV40 large-T-antigen-mediated activities. In particular, chimeric-T-antigen constructs in which the SV40 T-antigen J domain was replaced with that from the yeast Ydj1p or Escherichia coli DnaJ proteins failed to replicate in BSC40 cells and did not transform REF52 cells. However, T antigen containing the JC virus J domain was functional in these assays, although it was less efficient than the wild type. The inability of some large-T-antigen chimeras to promote DNA replication and elicit cellular transformation was not due to a failure to interact with hsc70, since a nonfunctional chimera, containing the DnaJ J domain, bound hsc70. However, this nonfunctional chimeric T antigen was reduced in its ability to stimulate hsc70 ATPase activity and unable to liberate E2F from p130, indicating that transcriptional activation of factors required for cell growth and DNA replication may be compromised. Our data suggest that the T-antigen J domain harbors species-specific elements required for viral activities in vivo. PMID:10891510

Molecular Characterization and the Function of Argonaute3 in RNAi Pathway of Plutella xylostella

PubMed Central

Hameed, Muhammad Salman; Wang, Zhengbing; Yang, Guang

2018-01-01

Argonaute (Ago) protein family plays a key role in the RNA interference (RNAi) process in different insects including Lepidopteran. However, the role of Ago proteins in the RNAi pathway of Plutella xylostella is still unknown. We cloned an Argonaute3 gene in P. xylostella (PxAgo3) with the complete coding sequence of 2832 bp. The encoded protein had 935 amino acids with an expected molecular weight of 108.9 kDa and an isoelectric point of 9.29. It contained a PAZ (PIWI/Argonaute/Zwile) domain and PIWI (P-element-induced whimpy testes) domain. PxAgo3 was classified into the Piwi subfamily of Ago proteins with a high similarity of 93.0% with Bombyx mori Ago3 (BmAgo3). The suppression of PxAgo3 by dsPxAgo3 was observed 3 h after treatment and was maintained until 24 h. Knockdown of PxAgo3 decreased the suppression level of PxActin by dsPxActin in P. xylostella cells, while overexpression of PxAgo3 increased the RNAi efficiency. Our results suggest that PxAgo3 play a key role in the double stranded RNA (dsRNA)-regulated RNAi pathway in P. xylostella. PMID:29677157

Molecular Characterization and the Function of Argonaute3 in RNAi Pathway of Plutella xylostella.

PubMed

Hameed, Muhammad Salman; Wang, Zhengbing; Vasseur, Liette; Yang, Guang

2018-04-20

Argonaute (Ago) protein family plays a key role in the RNA interference (RNAi) process in different insects including Lepidopteran. However, the role of Ago proteins in the RNAi pathway of Plutella xylostella is still unknown. We cloned an Argonaute3 gene in P. xylostella ( PxAgo3 ) with the complete coding sequence of 2832 bp. The encoded protein had 935 amino acids with an expected molecular weight of 108.9 kDa and an isoelectric point of 9.29. It contained a PAZ (PIWI/Argonaute/Zwile) domain and PIWI (P-element-induced whimpy testes) domain. PxAgo3 was classified into the Piwi subfamily of Ago proteins with a high similarity of 93.0% with Bombyx mori Ago3 (BmAgo3). The suppression of PxAgo3 by dsPxAgo3 was observed 3 h after treatment and was maintained until 24 h. Knockdown of PxAgo3 decreased the suppression level of PxActin by dsPxActin in P. xylostella cells, while overexpression of PxAgo3 increased the RNAi efficiency. Our results suggest that PxAgo3 play a key role in the double stranded RNA (dsRNA)-regulated RNAi pathway in P. xylostella .

A Note on NCOM Temperature Forecast Error Calibration Using the Ensemble Transform

DTIC Science & Technology

2009-01-01

Division Head Ruth H. Preller, 7300 Security, Code 1226 Office of Counsel,Code 1008.3 ADOR/Director NCST E. R. Franchi , 7000 Public Affairs...problem, local unbiased (correlation) and persistent errors (bias) of the Navy Coastal Ocean Modeling (NCOM) System nested in global ocean domains, are...system were made available in real-time without performing local data assimilation, though remote sensing and global data was assimilated on the

An efficient linear-scaling CCSD(T) method based on local natural orbitals.

PubMed

Rolik, Zoltán; Szegedy, Lóránt; Ladjánszki, István; Ladóczki, Bence; Kállay, Mihály

2013-09-07

An improved version of our general-order local coupled-cluster (CC) approach [Z. Rolik and M. Kállay, J. Chem. Phys. 135, 104111 (2011)] and its efficient implementation at the CC singles and doubles with perturbative triples [CCSD(T)] level is presented. The method combines the cluster-in-molecule approach of Li and co-workers [J. Chem. Phys. 131, 114109 (2009)] with frozen natural orbital (NO) techniques. To break down the unfavorable fifth-power scaling of our original approach a two-level domain construction algorithm has been developed. First, an extended domain of localized molecular orbitals (LMOs) is assembled based on the spatial distance of the orbitals. The necessary integrals are evaluated and transformed in these domains invoking the density fitting approximation. In the second step, for each occupied LMO of the extended domain a local subspace of occupied and virtual orbitals is constructed including approximate second-order Mo̸ller-Plesset NOs. The CC equations are solved and the perturbative corrections are calculated in the local subspace for each occupied LMO using a highly-efficient CCSD(T) code, which was optimized for the typical sizes of the local subspaces. The total correlation energy is evaluated as the sum of the individual contributions. The computation time of our approach scales linearly with the system size, while its memory and disk space requirements are independent thereof. Test calculations demonstrate that currently our method is one of the most efficient local CCSD(T) approaches and can be routinely applied to molecules of up to 100 atoms with reasonable basis sets.

Sense of coherence--a determinant of quality of life over time in older female acute myocardial infarction survivors.

PubMed

Norekvål, Tone M; Fridlund, Bengt; Moons, Philip; Nordrehaug, Jan E; Saevareid, Hans I; Wentzel-Larsen, Tore; Hanestad, Berit R

2010-03-01

To determine the relationships between different sense of coherence levels and quality of life, and in older female myocardial infarction survivors; to investigate how socio-demographic, clinical characteristics, sense of coherence self-reported symptoms and function affect quality of life; and to determine whether sense of coherence and quality of life are stable during a six-month follow-up. Myocardial infraction confers new physical and mental challenges. However, research on sense of coherence and other factors involved in maintaining physical, psychosocial and environmental aspects of quality of life in older female myocardial infraction survivors is scant. Survey. A postal survey was conducted of 145 women, aged 62-80 years, three months to five years after myocardial infarction (T1), with a follow-up after six months (T2). Self-reported socio-demographic and clinical data and hospital medical records data were collected. The sense of coherence scale (SOC-29) and the World Health Organization Quality of Life Instrument Abbreviated (WHOQOL-BREF) were used. We found a significant difference in quality of life between weak, moderate, and strong sense of coherence groups (p<0.001). Sense of coherence contributed to the level of all quality of life domains (p<0.001). Several clinical characteristics contributed to quality of life: (1) physical domain: comorbidities (p<0.001), previous myocardial infarction (p = 0.013), ejection fraction (p<0.011), length of hospital stay (p = 0.005) symptoms and function (p<0.001); (2) psychological domain: previous myocardial infarction (p = 0.031) and symptoms and function (p<0.001); and (3) environmental domain: education (p = 0.033) and symptoms and function (p = 0.003). On group level, both sense of coherence and quality of life were stable. Experiencing specific health changes (p<0.001), not major life events, influenced quality of life during the six-month follow-up. Sense of coherence was an important stable determinant of quality of life domains in female myocardial infarction survivors. Although other factors were identified, further research is needed to elucidate additional determinants of quality of life. These specific factors could guide clinicians in making treatment decisions that optimize the quality of life of their patients. Applying a salutogenic perspective through patient education may be important.

Complete mitochondrial genome sequence of northeastern sika deer (Cervus nippon hortulorum).

PubMed

Shao, Yuanchen; Zha, Daiming; Xing, Xiumei; Su, Weilin; Liu, Huamiao; Zhang, Ranran

2016-01-01

The complete mitochondrial genome of the northeastern sika deer, Cervus nippon hortulorum, was determined by accurate polymerase chain reaction. The entire genome is 16,434 bp in length and contains 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and 1 control region, all of which are arranged in a typical vertebrate manner. The overall base composition of the northeastern sika deer's mitochondrial genome is 33.3% of A, 24.5% of C, 28.7% of T and 13.5% of G. A termination associated sequence and several conserved central sequence block domains were discovered within the control region.

Cognitive functioning in young children with type 1 diabetes.

PubMed

Cato, M Allison; Mauras, Nelly; Ambrosino, Jodie; Bondurant, Aiden; Conrad, Amy L; Kollman, Craig; Cheng, Peiyao; Beck, Roy W; Ruedy, Katrina J; Aye, Tandy; Reiss, Allan L; White, Neil H; Hershey, Tamara

2014-02-01

The aim of this study was to assess cognitive functioning in children with type 1 diabetes (T1D) and examine whether glycemic history influences cognitive function. Neuropsychological evaluation of 216 children (healthy controls, n = 72; T1D, n = 144) ages 4-10 years across five DirecNet sites. Cognitive domains included IQ, Executive Functions, Learning and Memory, and Processing Speed. Behavioral, mood, parental IQ data, and T1D glycemic history since diagnosis were collected. The cohorts did not differ in age, gender or parent IQ. Median T1D duration was 2.5 years and average onset age was 4 years. After covarying age, gender, and parental IQ, the IQ and the Executive Functions domain scores trended lower (both p = .02, not statistically significant adjusting for multiple comparisons) with T1D relative to controls. Children with T1D were rated by parents as having more depressive and somatic symptoms (p < .001). Learning and memory (p = .46) and processing speed (p = .25) were similar. Trends in the data supported that the degree of hyperglycemia was associated with Executive Functions, and to a lesser extent, Child IQ and Learning and Memory. Differences in cognition are subtle in young children with T1D within 2 years of onset. Longitudinal evaluations will help determine whether these findings change or become more pronounced with time.

Cognitive functioning in young children with type 1 diabetes

PubMed Central

Cato, M. Allison; Mauras, Nelly; Ambrosino, Jodie; Bondurant, Aiden; Conrad, Amy L.; Kollman, Craig; Cheng, Peiyao; Beck, Roy W.; Ruedy, Katrina J.; Aye, Tandy; Reiss, Allan L.; White, Neil H.; Hershey, Tamara

2014-01-01

Objective To assess cognitive functioning in children with type 1 diabetes (T1D) and examine whether glycemic history influences cognitive function. Research Design and Methods Neuropsychological evaluation of 216 children (healthy controls, n = 72; T1D, n = 144) ages 4-10yrs across five DirecNet sites. Cognitive domains included IQ, Executive Functions, Learning and Memory, and Processing Speed. Behavioral, mood, parental IQ data and T1D glycemic history since diagnosis were collected. Results The cohorts did not differ in age, gender or parent IQ. Median T1D duration was 2.5yrs and average onset age was 4yrs. After covarying age, gender, and parental IQ, the IQ and the Executive Functions domain scores trended lower (both p = .02, not statistically significant adjusting for multiple comparisons) with T1D relative to controls. Children with T1D were rated by parents as having more depressive and somatic symptoms (p < 0.001). Learning and memory (p = 0.46) and processing speed (p = 0.25) were similar. Trends in the data supported that the degree of hyperglycemia was associated with Executive Functions, and to a lesser extent, Child IQ and Learning and Memory. Conclusions Differences in cognition are subtle in young children with T1D within 2 years of onset. Longitudinal evaluations will help determine whether these findings change or become more pronounced with time. PMID:24512675

Parallel deterministic neutronics with AMR in 3D

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

Clouse, C.; Ferguson, J.; Hendrickson, C.

1997-12-31

AMTRAN, a three dimensional Sn neutronics code with adaptive mesh refinement (AMR) has been parallelized over spatial domains and energy groups and runs on the Meiko CS-2 with MPI message passing. Block refined AMR is used with linear finite element representations for the fluxes, which allows for a straight forward interpretation of fluxes at block interfaces with zoning differences. The load balancing algorithm assumes 8 spatial domains, which minimizes idle time among processors.

Bacterially produced human B7-1 protein encompassing its complete extracellular domain maintains its costimulatory activity in vitro.

PubMed

Shen, W; Wang, Y; Geng, Y; Si, L

2000-08-01

To investigate which of the two immunoglobulin (Ig)-like domains, immunoglobulin variable region homologous domain IgV (hB7-1 IgV), or immunoglobulin constant region homologous domain IgC (hB7-1 IgC) on human B7-1 molecule contain the receptor binding sites, and to evaluate if the B7-1 molecule expressed in bacteria has biological activity. PCR was used to amplify three fragments of hB7-1 IgV, hB7-1 IgC and complete extracellular region of human B7-1 containing both the IgV and IgC domains (hB7-1 IgV + IgC). Three recombinants, pQE9-hB7-1 IgV, pQE9-hB7-1 IgC and pQE9-Hb7-1 (IgV + IgC) were generated by cloning the PCR products into a prokaryote expression plasmid (pQE-9) and were introduced into the host stain M15. The relevant target hexahistidine-tagged proteins were identified by SDS-PAGE and Western blotting. With the presence of the first signal imitated by anti-CD3 antibody, T cell activation was observed by exposing purified T lymphocytes to each soluble form of the three bacterially-produced human B7-1 proteins and [3H]-TdR incorporation. Three recombinant proteins of human B7-1, hB7-1 IgV, hB7-1 IgC and hB7-1 (IgV + IgC) were produced and detected in both soluble and inclusive body forms from engineered bacterial cells. With the presence of anti-CD3 antibody, T lymphocytes proliferated when co-stimulated by bacterially produced hB7-1 (IgV + IgC), but not by either hB7-1 IgV or hB7-1 IgC. Functional glycoprotein human B7-1 could be produced in bacterial cells. Both extracellular immunoglobulin-like domains are necessary for B7-1 to react with its counter receptors.

Decrease in heart rate variability with overtraining: assessment by the Poincaré plot analysis.

PubMed

Mourot, Laurent; Bouhaddi, Malika; Perrey, Stéphane; Cappelle, Sylvie; Henriet, Marie-Thérèse; Wolf, Jean-Pierre; Rouillon, Jean-Denis; Regnard, Jacques

2004-01-01

Numerous symptoms have been associated with the overtraining syndrome (OT), including changes in autonomic function. Heart rate variability (HRV) provides non-invasive data about the autonomic regulation of heart rate in real-life conditions. The aims of the study were to: (i) characterize the HRV profile of seven athletes (OA) diagnosed as suffering of OT, compared with eight healthy sedentary (C) and eight trained (T) subjects during supine rest and 60 degrees upright, and (ii) compare the traditional time- and frequency-domain analysis assessment of HRV with the non-linear Poincaré plot analysis. In the latter each R-R interval is plotted as a function of the previous one, and the standard deviations of the instantaneous (SD1) and long-term R-R interval variability are calculated. Total power was higher in T than in C and OA both in supine (1158 +/- 1137, 6092 +/- 3554 and 2970 +/- 2947 ms2 for C, T and OA, respectively) and in upright (640 +/- 499, 1814 +/- 806 and 1092 +/- 712 ms2 for C, T and OA, respectively; P<0.05) positions. In supine position, indicators of parasympathetic activity to the sinus node were higher in T compared with C and OA (high-frequency power: 419.1 +/- 381.2, 1105.3 +/- 781.4 and 463.7 +/- 715.8 ms2 for C, T and OA, respectively; P<0.05; SD1: 29.5 +/- 18.5, 75.2 +/- 17.2 and 37.6 +/- 27.5 for C, T and OA, respectively; P<0.05). OA had a marked predominance of sympathetic activity regardless of the position (LF/HF were 0.47 +/- 0.35, 0.47 +/- 0.50 and 3.96 +/- 5.71 in supine position for C, T and OA, respectively, and 2.09 +/- 2.17, 7.22 +/- 6.82 and 12.04 +/- 10.36 in upright position for C, T and OA, respectively). The changes in HRV indexes induced by the upright posture were greater in T than in OA. The shape of the Poincaré plots allowed the distinction between the three groups, with wide and narrow shapes in T and OA, respectively, compared with C. As Poincaré plot parameters are easy to compute and associated with the 'width' of the scatter gram, they corroborate the traditional time- and frequency-domain analysis. We suggest that they could be used to indicate fatigue and/or prevent OT.

Transcriptome-wide discovery of circular RNAs in Archaea

PubMed Central

Danan, Miri; Schwartz, Schraga; Edelheit, Sarit; Sorek, Rotem

2012-01-01

Circular RNA forms had been described in all domains of life. Such RNAs were shown to have diverse biological functions, including roles in the life cycle of viral and viroid genomes, and in maturation of permuted tRNA genes. Despite their potentially important biological roles, discovery of circular RNAs has so far been mostly serendipitous. We have developed circRNA-seq, a combined experimental/computational approach that enriches for circular RNAs and allows profiling their prevalence in a whole-genome, unbiased manner. Application of this approach to the archaeon Sulfolobus solfataricus P2 revealed multiple circular transcripts, a subset of which was further validated independently. The identified circular RNAs included expected forms, such as excised tRNA introns and rRNA processing intermediates, but were also enriched with non-coding RNAs, including C/D box RNAs and RNase P, as well as circular RNAs of unknown function. Many of the identified circles were conserved in Sulfolobus acidocaldarius, further supporting their functional significance. Our results suggest that circular RNAs, and particularly circular non-coding RNAs, are more prevalent in archaea than previously recognized, and might have yet unidentified biological roles. Our study establishes a specific and sensitive approach for identification of circular RNAs using RNA-seq, and can readily be applied to other organisms. PMID:22140119

Experimental evidence for negative turgor pressure in small leaf cells of Robinia pseudoacacia L versus large cells of Metasequoia glyptostroboides Hu et W.C. Cheng. 2. Höfler diagrams below the volume of zero turgor and the theoretical implication for pressure-volume curves of living cells.

PubMed

Yang, Dongmei; Li, Junhui; Ding, Yiting; Tyree, Melvin T

2017-03-01

The physiological advantages of negative turgor pressure, P t , in leaf cells are water saving and homeostasis of reactants. This paper advances methods for detecting the occurrence of negative P t in leaves. Biomechanical models of pressure-volume (PV) curves predict that negative P t does not change the linearity of PV curve plots of inverse balance pressure, P B , versus relative water loss, but it does predict changes in either the y-intercept or the x-intercept of the plots depending on where cell collapse occurs in the P B domain because of negative P t . PV curve analysis of Robinia leaves revealed a shift in the x-intercept (x-axis is relative water loss) of PV curves, caused by negative P t of palisade cells. The low x-intercept of the PV curve was explained by the non-collapse of palisade cells in Robinia in the P B domain. Non-collapse means that P t smoothly falls from positive to negative values with decreasing cell volume without a dramatic change in slope. The magnitude of negative turgor in non-collapsing living cells was as low as -1.3 MPa and the relative volume of the non-collapsing cell equaled 58% of the total leaf cell volume. This study adds to the growing evidence for negative P t . © 2016 John Wiley & Sons Ltd.

Simulation Procedure for Lifelong Flight Behavior of Electrons Consistent in Three Domains of Time t, Position x, and Energy ɛ

NASA Astrophysics Data System (ADS)

Ikuta, Nobuaki; Takeda, Akihide

2017-12-01

Research on the flight behavior of electrons and ions in a gas under an electric field has recently moved in a direction of clarifying the mechanism of the spatiotemporal development of a swarm, but the symbolic unknown state function f(r,c,t) of the Boltzmann equation has not been obtained in an explicit form. However, a few papers on the spatiotemporal development of an electron swarm using the Monte Carlo simulation have been published. On the other hand, a new simulation procedure for obtaining the lifelong state function FfT(t,x,ɛ) and local transport quantities J(t,x,ɛ) of electrons in the three domains of time t, one-dimensional position x, and energy ɛ under arbitrary initial and boundary conditions has been developed by extending the flight-time-integral (FTI) methods previously reported and is named the 3D-FTI method. A preliminary calculation has shown that this method can extensively provide the flight behavior of individual electrons in a swarm and local transport quantities consistent in the three domains with reasonable accuracy and career dependences.

IQGAP Proteins Reveal an Atypical Phosphoinositide (aPI) Binding Domain with a Pseudo C2 Domain Fold*

PubMed Central

Dixon, Miles J.; Gray, Alexander; Schenning, Martijn; Agacan, Mark; Tempel, Wolfram; Tong, Yufeng; Nedyalkova, Lyudmila; Park, Hee-Won; Leslie, Nicholas R.; van Aalten, Daan M. F.; Downes, C. Peter; Batty, Ian H.

2012-01-01

Class I phosphoinositide (PI) 3-kinases act through effector proteins whose 3-PI selectivity is mediated by a limited repertoire of structurally defined, lipid recognition domains. We describe here the lipid preferences and crystal structure of a new class of PI binding modules exemplified by select IQGAPs (IQ motif containing GTPase-activating proteins) known to coordinate cellular signaling events and cytoskeletal dynamics. This module is defined by a C-terminal 105–107 amino acid region of which IQGAP1 and -2, but not IQGAP3, binds preferentially to phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3). The binding affinity for PtdInsP3, together with other, secondary target-recognition characteristics, are comparable with those of the pleckstrin homology domain of cytohesin-3 (general receptor for phosphoinositides 1), an established PtdInsP3 effector protein. Importantly, the IQGAP1 C-terminal domain and the cytohesin-3 pleckstrin homology domain, each tagged with enhanced green fluorescent protein, were both re-localized from the cytosol to the cell periphery following the activation of PI 3-kinase in Swiss 3T3 fibroblasts, consistent with their common, selective recognition of endogenous 3-PI(s). The crystal structure of the C-terminal IQGAP2 PI binding module reveals unexpected topological similarity to an integral fold of C2 domains, including a putative basic binding pocket. We propose that this module integrates select IQGAP proteins with PI 3-kinase signaling and constitutes a novel, atypical phosphoinositide binding domain that may represent the first of a larger group, each perhaps structurally unique but collectively dissimilar from the known PI recognition modules. PMID:22493426

IQGAP Proteins Reveal an Atypical Phosphoinositide (aPI) Binding Domain with a Pseudo C2 Domain Fold

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

Dixon, Miles J.; Gray, Alexander; Schenning, Martijn

2012-10-16

Class I phosphoinositide (PI) 3-kinases act through effector proteins whose 3-PI selectivity is mediated by a limited repertoire of structurally defined, lipid recognition domains. We describe here the lipid preferences and crystal structure of a new class of PI binding modules exemplified by select IQGAPs (IQ motif containing GTPase-activating proteins) known to coordinate cellular signaling events and cytoskeletal dynamics. This module is defined by a C-terminal 105-107 amino acid region of which IQGAP1 and -2, but not IQGAP3, binds preferentially to phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3). The binding affinity for PtdInsP3, together with other, secondary target-recognition characteristics, are comparable with those ofmore » the pleckstrin homology domain of cytohesin-3 (general receptor for phosphoinositides 1), an established PtdInsP3 effector protein. Importantly, the IQGAP1 C-terminal domain and the cytohesin-3 pleckstrin homology domain, each tagged with enhanced green fluorescent protein, were both re-localized from the cytosol to the cell periphery following the activation of PI 3-kinase in Swiss 3T3 fibroblasts, consistent with their common, selective recognition of endogenous 3-PI(s). The crystal structure of the C-terminal IQGAP2 PI binding module reveals unexpected topological similarity to an integral fold of C2 domains, including a putative basic binding pocket. We propose that this module integrates select IQGAP proteins with PI 3-kinase signaling and constitutes a novel, atypical phosphoinositide binding domain that may represent the first of a larger group, each perhaps structurally unique but collectively dissimilar from the known PI recognition modules.« less

Recognition of p63 by the E3 ligase ITCH: Effect of an ectodermal dysplasia mutant.

PubMed

Bellomaria, A; Barbato, Gaetano; Melino, G; Paci, M; Melino, Sonia

2010-09-15

The E3 ubiquitin ligase Itch mediates the degradation of the p63 protein. Itch contains four WW domains which are pivotal for the substrate recognition process. Indeed, this domain is implicated in several signalling complexes crucially involved in human diseases including Muscular Dystrophy, Alzheimer's Disease and Huntington Disease. WW domains are highly compact protein-protein binding modules that interact with short proline-rich sequences. The four WW domains present in Itch belong to the Group I type, which binds polypeptides with a PY motif characterized by a PP xY consensus sequence, where x can be any residue. Accordingly, the Itch-p63 interaction results from a direct binding of Itch-WW2 domain with the PY motif of p63. Here, we report a structural analysis of the Itch-p63 interaction by fluorescence, CD and NMR spectroscopy. Indeed, we studied the in vitro interaction between Itch-WW2 domain and p63(534-551), an 18-mer peptide encompassing a fragment of the p63 protein including the PY motif. In addition, we evaluated the conformation and the interaction with Itch-WW2 of a site specific mutant of p63, I549T, that has been reported in both Hay-Wells syndrome and Rapp-Hodgkin syndrome. Based on our results, we propose an extended PP xY motif for the Itch recognition motif (P-P-P-Y-x(4)-[ST]-[ILV]), which includes these C-terminal residues to the PP xY motif.

Role of two adaptor molecules SLP-76 and LAT in the PI3K signaling pathway in activated T cells.

PubMed

Shim, Eun Kyung; Jung, Seung Hee; Lee, Jong Ran

2011-03-01

Previously, we identified p85, a subunit of PI3K, as one of the molecules that interacts with the N-terminal region of Src homology 2 domain-containing leukocyte protein of 76 kDa (SLP-76). We also demonstrated that tyrosine phosphorylation either at the 113 and/or 128 position is sufficient for the association of SLP-76 with the Src homology 2 domain near the N terminus of p85. The present study further examines the role of the association of these two molecules on the activation of PI3K signaling cascade. Experiments were done to determine the role of SLP-76, either wild-type, tyrosine mutants, or membrane-targeted forms of various SLP-76 constructs, on the membrane localization and phosphorylation of Akt, which is an event downstream of PI3K activation. Reconstitution studies with these various SLP-76 constructs in a Jurkat variant cell line that lacks SLP-76 or linker for activation of T cells (LAT) show that the activation of PI3K pathway following TCR ligation requires both SLP-76 and LAT adaptor proteins. The results suggest that SLP-76 associates with p85 after T cell activation and that LAT recruits this complex to the membrane, leading to Akt activation.

Normal and keratoconic corneal epithelial thickness mapping using Fourier-domain optical coherence tomography

NASA Astrophysics Data System (ADS)

Li, Yan; Tan, Ou; Huang, David

2011-03-01

The detection of early-stage keratoconus is one of the most important safety issues in screening candidates for corneal refractive surgeries. We propose to use epithelial thickness maps to assist the diagnosis of keratoconus. The corneal epithelial thickness in normal and keratoconic eyes was mapped with optical coherence tomography (OCT). A Fourier-domain OCT system capable of acquiring 26,000 axial-scans per second was used. It has an axial resolution of 5μm in cornea. A pachymetry scan pattern (8 radials, 1024 axial-scans each, 6mm diameter, repeat 3 times) centered at the pupil center was used to image the cornea. The 3 repeated radial scans on each meridian were registered and averaged. Then the anterior corneal, posterior corneal and epithelial boundaries were segmented automatically with a computer algorithm by increased signal intensity at corresponding boundaries. The epithelial thickness map was generated by interpolating epithelial thickness profile calculated from each meridian. Normal and keratoconic eyes (24 eyes each) were scanned 3 times. The central epithelial thickness in normal eyes was thicker than those of keratoconic eyes (mean difference 2.1 μm, t-test p=0.05). The epithelium was thinner superiorly than inferiorly in normal eyes (mean difference -1.4+/-1.1μm, p<0.001) while thicker superiorly than inferiorly in keratoconic eyes (2.0+/-4.1 μm, p=0.02).

Translation and Validation of the Farage Quality of Life (FQoL™) Instrument for Consumer Products into Traditional Chinese

PubMed Central

Farage, Miranda A.; Rodenberg, Cindy; Chen, Jasmine

2013-01-01

The Farage Quality of Life™ questionnaire (FQoL™) was developed specifically to assess the impact of consumer products. The objective of this investigation was to achieve a Chinese language instrument. The FQoL™ underwent a forward and backward translation, with cognitive testing by 13 subjects. Slight modifications were made to the instrument, and an implementation study was conducted with 800 participants having a mean (±SD) age of 34.22 (±9.28) years. The subjects were randomly assigned to use 1 of 4 ultra absorbency pad products for the length of one menstrual cycle. Three pads (coded N, S and C) were products currently available on the retail market, a fourth (coded M) was an experimental product improvement on Product N. Subjects were asked to complete the FQoL™ once before (T1) and once after (T2) the start of their period, and the Least Square (LS) Means were determined. Within group comparisons for each item and FQoL™ subscale were conducted by comparing the LS Means for T1 vs. T2. Participants using Product N showed the highest number of significant (p<0.05) changes (11 items), demonstrating these subjects felt worse about items mainly in the subdomains for Emotions, Personal Pleasure, and Physical State. Participants using Product C showed significant changes in 7 items mainly in the subdomains for Emotion and Physical State. Participants using Product S and the experimental Product M showed significant changes in only 4 and 3 individual items, respectively. These were not associated with any particular domain or subdomain. Between group comparisons were conducted by comparing the LS Means for the T2 responses for each group. The group using Product N had LS Mean responses that were significantly worse than the group using Product M for the Emotion, Personal Pleasure and Physical State subdomains, the Energy/Vitality domain, and 2 individual items. The Product S group was worse than the Product M group for 2 individual items. The Product C group was worse than the Product M group for the Personal Pleasure and Physical State subdomains and 5 individual items. We found that the Chinese language FQoL™ detected changes in HRQoL during menstruation compared with before menstruation. Further, the measure was able to detect differences among groups of subjects using different menstrual protection products. PMID:23283031

Optical, electrical and elastic properties of ferroelectric domain walls in lithium niobate and lithium titanate

NASA Astrophysics Data System (ADS)

Kim, Sungwon

Ferroelectric LiNbO3 and LiTaO3 crystals have developed, over the last 50 years as key materials for integrated and nonlinear optics due to their large electro-optic and nonlinear optical coefficients and a broad transparency range from 0.4 mum-4.5 mum wavelengths. Applications include high speed optical modulation and switching in 40GHz range, second harmonic generation, optical parametric amplification, pulse compression and so on. Ferroelectric domain microengineering has led to electro-optic scanners, dynamic focusing lenses, total internal reflection switches, and quasi-phase matched (QPM) frequency doublers. Most of these applications have so far been on non-stoichiometric compositions of these crystals. Recent breakthroughs in crystal growth have however opened up an entirely new window of opportunity from both scientific and technological viewpoint. The growth of stoichiometric composition crystals has led to the discovery of many fascinating effects arising from the presence or absence of atomic defects, such as an order of magnitude changes in coercive fields, internal fields, domain backswitching and stabilization phenomenon. On the nanoscale, unexpected features such as the presence of wide regions of optical contrast and strain have been discovered at 180° domain walls. Such strong influence of small amounts of nonstoichiometric defects on material properties has led to new device applications, particularly those involving domain patterning and shaping such as QPM devices in thick bulk crystals and improved photorefractive damage compositions. The central focus of this dissertation is to explore the role of nonstoichiometry and its precise influence on macroscale and nanoscale properties in lithium niobate and tantalate. Macroscale properties are studied using a combination of in-situ and high-speed electro-optic imaging microscopy and electrical switching experiments. Local static and dynamic strain properties at individual domain walls is studied using X-ray synchrotron imaging with and without in-situ electric fields. Nanoscale optical properties are studied using Near Field Scanning Optical Microscopy(NSOM). Finite Difference Time Domain(FDTD) codes, Beam Propagation Method(BPM) codes and X-ray tracing codes have been developed to successfully simulate NSOM images and X-ray topography images to extract the local optical and strain properties, respectively. A 3-D ferroelectric domain simulation code based on Time Dependent Ginzburg Landau(TDGL) theory and group theory has been developed to understand the nature of these local wall strains and the preferred wall orientations. By combining these experimental and numerical tools, We have also proposed a defect-dipole model and a mechanism by which the defect interacts with the domain walls. This thesis has thus built a more comprehensive picture of the influence of defects on domain walls on nanoscale and macroscale, and raises new scientific questions about the exact nature of domain walls-defect interactions. Besides the specific problem of ferroelectrics, the experimental and simulation tools, developed in this thesis will have wider application in the area of materials science.

FOLDING OF DIPHTHERIA TOXIN T-DOMAIN IN THE PRESENCE OF AMPHIPOLS AND FLUORINATED SURFACTANTS: TOWARD THERMODYNAMIC MEASUREMENTS OF MEMBRANE PROTEIN FOLDING

PubMed Central

Kyrychenko, Alexander; Rodnin, Mykola V.; Vargas-Uribe, Mauricio; Sharma, Shivaji K.; Durand, Grégory; Pucci, Bernard; Popot, Jean-Luc; Ladokhin, Alexey S.

2011-01-01

Solubilizing membrane proteins for functional, structural and thermodynamic studies is usually achieved with the help of detergents, which tend to destabilize them, however. Several classes of non-detergent surfactants have been designed as milder substitutes for detergents, most prominently amphipathic polymers called 'amphipols' and fluorinated surfactants. Here we test the potential usefulness of these compounds for thermodynamic studies by examining their effect on conformational transitions of the diphtheria toxin T-domain. The advantage of the T-domain as a model system is that it exists as a soluble globular protein at neutral pH yet is converted into a membrane-competent form by acidification and inserts into the lipid bilayer as part of its physiological action. We have examined the effects of various surfactants on two conformational transitions of the T-domain, thermal unfolding and pH-induced transition to a membrane-competent form. All tested detergent and non-detergent surfactants lowered the cooperativity of the thermal unfolding of the T-domain. The dependence of enthalpy of unfolding on surfactant concentration was found to be least for fluorinated surfactants, thus making them useful candidates for thermodynamic studies. Circular dichroism measurements demonstrate that non-ionic homo-polymeric amphipols (NAhPols), unlike any other surfactants, can actively cause a conformational change of the T-domain. NAhPol-induced structural rearrangements are different from those observed during thermal denaturation and are suggested to be related to the formation of the membrane-competent form of the T-domain. Measurements of vesicle content leakage indicate that interaction with NAhPols not only does not prevent the T-domain from inserting into the bilayer, but it can make bilayer permeabilization even more efficient, whereas the pH-dependence of membrane permeabilization becomes more cooperative. PMID:21945883

Finite difference time domain grid generation from AMC helicopter models

NASA Technical Reports Server (NTRS)

Cravey, Robin L.

1992-01-01

A simple technique is presented which forms a cubic grid model of a helicopter from an Aircraft Modeling Code (AMC) input file. The AMC input file defines the helicopter fuselage as a series of polygonal cross sections. The cubic grid model is used as an input to a Finite Difference Time Domain (FDTD) code to obtain predictions of antenna performance on a generic helicopter model. The predictions compare reasonably well with measured data.

H3.3 demarcates GC-rich coding and subtelomeric regions and serves as potential memory mark for virulence gene expression in Plasmodium falciparum

PubMed Central

Fraschka, Sabine Anne-Kristin; Henderson, Rob Wilhelmus Maria; Bártfai, Richárd

2016-01-01

Histones, by packaging and organizing the DNA into chromatin, serve as essential building blocks for eukaryotic life. The basic structure of the chromatin is established by four canonical histones (H2A, H2B, H3 and H4), while histone variants are more commonly utilized to alter the properties of specific chromatin domains. H3.3, a variant of histone H3, was found to have diverse localization patterns and functions across species but has been rather poorly studied in protists. Here we present the first genome-wide analysis of H3.3 in the malaria-causing, apicomplexan parasite, P. falciparum, which revealed a complex occupancy profile consisting of conserved and parasite-specific features. In contrast to other histone variants, PfH3.3 primarily demarcates euchromatic coding and subtelomeric repetitive sequences. Stable occupancy of PfH3.3 in these regions is largely uncoupled from the transcriptional activity and appears to be primarily dependent on the GC-content of the underlying DNA. Importantly, PfH3.3 specifically marks the promoter region of an active and poised, but not inactive antigenic variation (var) gene, thereby potentially contributing to immune evasion. Collectively, our data suggest that PfH3.3, together with other histone variants, indexes the P. falciparum genome to functionally distinct domains and contribute to a key survival strategy of this deadly pathogen. PMID:27555062

Salvus: A flexible open-source package for waveform modelling and inversion from laboratory to global scales

NASA Astrophysics Data System (ADS)

Afanasiev, M.; Boehm, C.; van Driel, M.; Krischer, L.; May, D.; Rietmann, M.; Fichtner, A.

2016-12-01

Recent years have been witness to the application of waveform inversion to new and exciting domains, ranging from non-destructive testing to global seismology. Often, each new application brings with it novel wave propagation physics, spatial and temporal discretizations, and models of variable complexity. Adapting existing software to these novel applications often requires a significant investment of time, and acts as a barrier to progress. To combat these problems we introduce Salvus, a software package designed to solve large-scale full-waveform inverse problems, with a focus on both flexibility and performance. Based on a high order finite (spectral) element discretization, we have built Salvus to work on unstructured quad/hex meshes in both 2 or 3 dimensions, with support for P1-P3 bases on triangles and tetrahedra. A diverse (and expanding) collection of wave propagation physics are supported (i.e. coupled solid-fluid). With a focus on the inverse problem, functionality is provided to ease integration with internal and external optimization libraries. Additionally, a python-based meshing package is included to simplify the generation and manipulation of regional to global scale Earth models (quad/hex), with interfaces available to external mesh generators for complex engineering-scale applications (quad/hex/tri/tet). Finally, to ensure that the code remains accurate and maintainable, we build upon software libraries such as PETSc and Eigen, and follow modern software design and testing protocols. Salvus bridges the gap between research and production codes with a design based on C++ mixins and Python wrappers that separates the physical equations from the numerical core. This allows domain scientists to add new equations using a high-level interface, without having to worry about optimized implementation details. Our goal in this presentation is to introduce the code, show several examples across the scales, and discuss some of the extensible design points.

Salvus: A flexible high-performance and open-source package for waveform modelling and inversion from laboratory to global scales

NASA Astrophysics Data System (ADS)

Afanasiev, Michael; Boehm, Christian; van Driel, Martin; Krischer, Lion; May, Dave; Rietmann, Max; Fichtner, Andreas

2017-04-01

Recent years have been witness to the application of waveform inversion to new and exciting domains, ranging from non-destructive testing to global seismology. Often, each new application brings with it novel wave propagation physics, spatial and temporal discretizations, and models of variable complexity. Adapting existing software to these novel applications often requires a significant investment of time, and acts as a barrier to progress. To combat these problems we introduce Salvus, a software package designed to solve large-scale full-waveform inverse problems, with a focus on both flexibility and performance. Currently based on an abstract implementation of high order finite (spectral) elements, we have built Salvus to work on unstructured quad/hex meshes in both 2 or 3 dimensions, with support for P1-P3 bases on triangles and tetrahedra. A diverse (and expanding) collection of wave propagation physics are supported (i.e. viscoelastic, coupled solid-fluid). With a focus on the inverse problem, functionality is provided to ease integration with internal and external optimization libraries. Additionally, a python-based meshing package is included to simplify the generation and manipulation of regional to global scale Earth models (quad/hex), with interfaces available to external mesh generators for complex engineering-scale applications (quad/hex/tri/tet). Finally, to ensure that the code remains accurate and maintainable, we build upon software libraries such as PETSc and Eigen, and follow modern software design and testing protocols. Salvus bridges the gap between research and production codes with a design based on C++ template mixins and Python wrappers that separates the physical equations from the numerical core. This allows domain scientists to add new equations using a high-level interface, without having to worry about optimized implementation details. Our goal in this presentation is to introduce the code, show several examples across the scales, and discuss some of the extensible design points.

Aerothermo-Structural Analysis of Low Cost Composite Nozzle/Inlet Components

NASA Technical Reports Server (NTRS)

Shivakumar, Kuwigai; Challa, Preeli; Sree, Dave; Reddy, D.

1999-01-01

This research is a cooperative effort among the Turbomachinery and Propulsion Division of NASA Glenn, CCMR of NC A&T State University, and the Tuskegee University. The NC A&T is the lead center and Tuskegee University is the participating institution. Objectives of the research were to develop an integrated aerodynamic, thermal and structural analysis code for design of aircraft engine components, such as, nozzles and inlets made of textile composites; conduct design studies on typical inlets for hypersonic transportation vehicles and setup standards test examples and finally manufacture a scaled down composite inlet. These objectives are accomplished through the following seven tasks: (1) identify the relevant public domain codes for all three types of analysis; (2) evaluate the codes for the accuracy of results and computational efficiency; (3) develop aero-thermal and thermal structural mapping algorithms; (4) integrate all the codes into one single code; (5) write a graphical user interface to improve the user friendliness of the code; (6) conduct test studies for rocket based combined-cycle engine inlet; and finally (7) fabricate a demonstration inlet model using textile preform composites. Tasks one, two and six are being pursued. Selected and evaluated NPARC for flow field analysis, CSTEM for in-depth thermal analysis of inlets and nozzles and FRAC3D for stress analysis. These codes have been independently verified for accuracy and performance. In addition, graphical user interface based on micromechanics analysis for laminated as well as textile composites was developed. Demonstration of this code will be made at the conference. A rocket based combined cycle engine was selected for test studies. Flow field analysis of various inlet geometries were studied. Integration of codes is being continued. The codes developed are being applied to a candidate example of trailblazer engine proposed for space transportation. A successful development of the code will provide a simpler, faster and user-friendly tool for conducting design studies of aircraft and spacecraft engines, applicable in high speed civil transport and space missions.

Health-Related Quality of Life in Relation to Obesity Grade, Type 2 Diabetes, Metabolic Syndrome and Inflammation.

PubMed

Slagter, Sandra N; van Vliet-Ostaptchouk, Jana V; van Beek, André P; Keers, Joost C; Lutgers, Helen L; van der Klauw, Melanie M; Wolffenbuttel, Bruce H R

2015-01-01

Health-related quality of life (HR-QoL) may be compromised in obese individuals, depending on the presence of other complications. The aim of this study is to assess the effect of obesity-related conditions on HR-QoL. These conditions are i) grade of obesity with and without type 2 diabetes (T2D), ii) metabolic syndrome (MetS), and iii) level of inflammation. From the Dutch LifeLines Cohort Study we included 13,686 obese individuals, aged 18-80 years. HR-QoL was measured with the RAND 36-Item Health Survey which encompasses eight health domains. We calculated the percentage of obese individuals with poor HR-QoL, i.e. those scoring below the domain and sex specific cut-off value derived from the normal weight population. Logistic regression analysis was used to calculate the probability of having poor domain scores according to the conditions under study. Higher grades of obesity and the additional presence of T2D were associated with lower HR-QoL, particularly in the domains physical functioning (men: odds ratios (ORs) 1.48-11.34, P<0.005, and women: ORs 1.66-5.05, P<0.001) and general health (men: ORs 1.44-3.07, P<0.005, and women: ORs 1.36-3.73, P<0.001). A higher percentage of obese individuals with MetS had a poor HR-QoL than those without MetS. Furthermore, we observed a linear trend between inflammation and the percentage of obese individuals with poor scores on the HR-QoL domains. Individuals with MetS were more likely to have poor scores in the domains general health, vitality, social functioning and role limitations due to emotional problems. Obese women with increased inflammation levels were more likely to have poor scores on all domains except role limitations due to emotional problems and mental health. The impact of obesity on an individual's quality of life is enhanced by grade of obesity, T2D, MetS and inflammation and are mainly related to reduced physical health. The mental well-being is less often impaired.

Mitogenic signals and transforming potential of Nyk, a newly identified neural cell adhesion molecule-related receptor tyrosine kinase.

PubMed Central

Ling, L; Kung, H J

1995-01-01

Nyk/Mer is a recently identified receptor tyrosine kinase with neural cell adhesion molecule-like structure (two immunoglobulin G-like domains and two fibronectin III-like domains) in its extracellular region and belongs to the Ufo/Axl family of receptors. The ligand for Nyk/Mer is presently unknown, as are the signal transduction pathways mediated by this receptor. We constructed and expressed a chimeric receptor (Fms-Nyk) composed of the extracellular domain of the human colony-stimulating factor 1 receptor (Fms) and the transmembrane and cytoplasmic domains of human Nyk/Mer in NIH 3T3 fibroblasts in order to investigate the mitogenic signaling and biochemical properties of Nyk/Mer. Colony-stimulating factor 1 stimulation of the Fms-Nyk chimeric receptor in transfected NIH 3T3 fibroblasts leads to a transformed phenotype and generates a proliferative response in the absence of other growth factors. We show that phospholipase C gamma, phosphatidylinositol 3-kinase/p70 S6 kinase, Shc, Grb2, Raf-1, and mitogen-activated protein kinase are downstream components of the Nyk/Mer signal transduction pathways. In addition, Nyk/Mer weakly activates p90rsk, while stress-activated protein kinase, Ras GTPase-activating protein (GAP), and GAP-associated p62 and p190 proteins are not activated or tyrosine phosphorylated by Nyk/Mer. An analysis comparing the Nyk/Mer signal cascade with that of the epidermal growth factor receptor indicates substrate preferences by these two receptors. Our results provide a detailed description of the Nyk/Mer signaling pathways. Given the structural similarity between the Ufo/Axl family receptors, some of the information may also be applied to other members of this receptor tyrosine kinase family. PMID:8524223

Comparative analysis of barophily-related amino acid content in protein domains of Pyrococcus abyssi and Pyrococcus furiosus.

PubMed

Yafremava, Liudmila S; Di Giulio, Massimo; Caetano-Anollés, Gustavo

2013-01-01

Amino acid substitution patterns between the nonbarophilic Pyrococcus furiosus and its barophilic relative P. abyssi confirm that hydrostatic pressure asymmetry indices reflect the extent to which amino acids are preferred by barophilic archaeal organisms. Substitution patterns in entire protein sequences, shared protein domains defined at fold superfamily level, domains in homologous sequence pairs, and domains of very ancient and very recent origin now provide further clues about the environment that led to the genetic code and diversified life. The pyrococcal proteomes are very similar and share a very early ancestor. Relative amino acid abundance analyses showed that biases in the use of amino acids are due to their shared fold superfamilies. Within these repertoires, only two of the five amino acids that are preferentially barophilic, aspartic acid and arginine, displayed this preference significantly and consistently across structure and in domains appearing in the ancestor. The more primordial asparagine, lysine and threonine displayed a consistent preference for nonbarophily across structure and in the ancestor. Since barophilic preferences are already evident in ancient domains that are at least ~3 billion year old, we conclude that barophily is a very ancient trait that unfolded concurrently with genetic idiosyncrasies in convergence towards a universal code.

T cells bearing a chimeric antigen receptor against prostate-specific membrane antigen mediate vascular disruption and result in tumor regression

PubMed Central

Santoro, Stephen P.; Kim, Soorin; Motz, Gregory T.; Alatzoglou, Dimitrios; Li, Chunsheng; Irving, Melita; Powell, Daniel J.; Coukos, George

2014-01-01

Aberrant blood vessels enable tumor growth, provide a barrier to immune infiltration, and serve as a source of pro-tumorigenic signals. Targeting tumor blood vessels for destruction, or tumor vascular disruption therapy, can therefore provide significant therapeutic benefit. Here we describe the ability of chimeric antigen receptor (CAR)-bearing T cells to recognize human prostate-specific membrane antigen (hPSMA) on endothelial targets in vitro as well as in vivo. CAR T cells were generated using the anti-PSMA scFv, J591, and the intracellular signaling domains: CD3ζ, CD28, and/or CD137/4-1BB. We found that all anti-hPSMA CAR T cells recognized and eliminated PSMA+ endothelial targets in vitro, regardless of the signaling domain. T cells bearing the 3rd generation anti-hPSMA CAR, P28BBζ, were able to recognize and kill primary human endothelial cells isolated from gynecologic cancers. In addition, the P28BBζ CAR T cells mediated regression of hPSMA-expressing vascular neoplasms in mice. Finally, in murine models of ovarian cancers populated by murine vessels expressing hPSMA, the P28BBζ CAR T cells were able to ablate PSMA+ vessels, cause secondary depletion of tumor cells, and reduce tumor burden. Taken together, these results provide strong rationale for the use of CAR T cells as agents of tumor vascular disruption, specifically those targeting PSMA. PMID:25358763

Extended Impact of Pin1 Catalytic Loop Phosphorylation Revealed by S71E Phosphomimetic.

PubMed

Mahoney, Brendan J; Zhang, Meiling; Zintsmaster, John S; Peng, Jeffrey W

2018-03-02

Pin1 is a two-domain human protein that catalyzes the cis-trans isomerization of phospho-Ser/Thr-Pro (pS/T-P) motifs in numerous cell-cycle regulatory proteins. These pS/T-P motifs bind to Pin1's peptidyl-prolyl isomerase (PPIase) domain in a catalytic pocket, between an extended catalytic loop and the PPIase domain core. Previous studies showed that post-translational phosphorylation of S71 in the catalytic loop decreases substrate binding affinity and isomerase activity. To define the origins for these effects, we investigated a phosphomimetic Pin1 mutant, S71E-Pin1, using solution NMR. We find that S71E perturbs not only its host loop but also the nearby PPIase core. The perturbations identify a local network of hydrogen bonds and salt bridges that is more extended than previously thought, and includes interactions between the catalytic loop and the α2/α3 turn in the PPIase core. Explicit-solvent molecular dynamics simulations and phylogenetic analysis suggest that these interactions act as conserved "latches" between the loop and PPIase core that enhance binding of phosphorylated substrates, as they are absent in PPIases lacking pS/T-P specificity. Our results suggest that S71 is a hub residue within an electrostatic network primed for phosphorylation, and may illustrate a common mechanism of phosphorylation-mediated allostery. Copyright © 2018 Elsevier Ltd. All rights reserved.

Predicted and measured retinal nerve fiber layer thickness from time-domain optical coherence tomography compared with spectral-domain optical coherence tomography.

PubMed

Schrems, Wolfgang A; Schrems-Hoesl, Laura M; Bendschneider, Delia; Mardin, Christian Y; Laemmer, Robert; Kruse, Friedrich E; Horn, Folkert K

2015-10-01

New methods are needed to compare peripapillary retinal nerve fiber layer thickness (pRNFLT) measurements taken from time-domain optical coherence tomography (TD-OCT) and spectral-domain OCT (SD-OCT). To compare the agreement of measured and predicted pRNFLT using different equations based on pRNFLT measurements obtained by TD-OCT and SD-OCT. Cross-sectional single-center study that took place at the Department of Ophthalmology, University of Erlangen-Nuremberg from November 16, 2005, to June 3, 2015, and included 138 eyes of control participants, 126 eyes of patients with ocular hypertension, 128 eyes of patients with preperimetric glaucoma, and 160 eyes of patients with perimetric glaucoma. All participants had standard clinical examinations to obtain TD-OCT (via Stratus OCT) and SD-OCT (via Spectralis OCT) measurements of pRNFLT. Two groups were matched for diagnostic subgroup, eye side, sex, and age. The TD-OCT measurements of the first group were used to predict the mean SD-OCT and 6-sector vertical-split pRNFLT measurements of the second group and vice versa. The agreement between the predicted pRNFLT calculations of conversion equations and measured pRNFLT of the second group was evaluated by intraclass correlation coefficients and Bland-Altman plots. Mean and sectoral pRNFLT measurements obtained by TD-OCT and SD-OCT as well as the agreement between measured and predicted pRNFLT. The agreement for all investigated equations to predict mean pRNFLT measurements with intraclass correlation coeffecients ranged from 0.937 to 0.939. Bland-Altman plots demonstrated systemic biases between -0.7 μm and +1.1 μm for measured and predicted mean pRNFLT measurements. The ratio method demonstrated an intraclass correlation coefficient of 0.969 for the temporal-inferior sector. The best color-code agreement between both OCT devices was achieved by the no conversion method, with κ = 0.731 (95% CI, 0.656-0.806) for the mean pRNFLT. These data suggest that the prediction of mean pRNFLT values by equations derived from TD-OCT and SD-OCT can be conducted with high levels of agreement. In individual cases and singular sectors, high prediction errors may occur. When longitudinal imaging data from both TD-OCT and SD-OCT are available, conversion equations may provide longitudinal comparability.

A Viscoelastic-Plastic Constitutive Model with a Finite Element Solution Methodology

DTIC Science & Technology

1978-06-01

where - r3 K f BT D B dv (4-15) • ,re E,,rae v ’,vp ,vp w F BT dv (4-17)A -vp -Vp 84 ii T In the above, K is the global viscoelastic stiffness matrix anl ...Code C4AA Port Hueneme. CA NAVSE ASYSCOM Code OOC (LT R. MacDougisl). Washington DC NAVSEC Code 6034 1 Library). Washington DC NAVSEC61RLACT PWO. Torni...ESEARCH CO LA HABRA, CA iBROOKSi 0ONCRFE It Il FCH-NoIOGY CORP. TACOMA. ’A At( ANL )ESONi ((tNRAI) ASSOC. Van NuNs CA iA. Luisonit I)RA Vt COR(P I’muitt

Just-in-Time to Save Lives: A Pilot Study of Layperson Tourniquet Application.

PubMed

Goolsby, Craig; Branting, Andrew; Chen, Elizabeth; Mack, Erin; Olsen, Cara

2015-09-01

The objective was to determine whether just-in-time (JiT) instructions increase successful tourniquet application by laypersons. This was a randomized pilot study conducted in August 2014. The study occurred at the Uniformed Services University campus in Bethesda, Maryland. A total of 194 volunteers without prior military service or medical training completed the study. The participant stood in front of a waist-down mannequin that had an exposed leg. An observer read a scenario card aloud that described a mass casualty event. The observer then asked the participant to apply a Combat Application Tourniquet (C-A-T) to the mannequin. Test participants received a 4 × 6-inch card, with JiT instructions, in addition to their C-A-T; controls received no instructions. Participants were randomized in a 3:1 ratio of instructions to no instructions. The study's primary outcome was the proportion of successfully applied tourniquets by participants receiving JiT instructions compared to participants not receiving instructions. Secondary outcomes included the time for successful tourniquet placement, reasons for failed tourniquet application, and participants' self-reported willingness and comfort using tourniquets in real-life settings. Just-in-time instructions more than doubled successful tourniquet placement. Participants supplied with JiT instructions placed a tourniquet successfully 44.14% of the time, compared to 20.41% of the time for controls without instructions (risk ratio = 2.16; 95% confidence interval = 1.21 to 3.87; p = 0.003). Just-in-time instructions increase laypeople's successful application of C-A-T. This pilot study provides evidence that JiT instructions may assist the lay public in providing effective point-of-injury hemorrhage control. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

Seismic velocity anisotropy and heterogeneity beneath the Mantle Electromagnetic and Tomography Experiment (MELT) region of the East Pacific Rise from analysis of P and S body waves

USGS Publications Warehouse

Hammond, W.C.; Toomey, D.R.

2003-01-01

We use teleseismic P and S delay times and shear wave splitting measurements to constrain isotropic and anisotropic heterogeneity in the mantle beneath the southern East Pacific Rise (SEPR). The data comprise 462 P and S delay times and 18 shear wave splitting observations recorded during the Mantle Electromagnetic and Tomography (MELT) Experiment. We estimate the mantle melt content (F) and temperature (T) variation from the isotropic velocity variation. Our results indicate that the maximum variation in F beneath our array is between zero and ???1.2%, and maximum variation in T is between zero and ???100 K. We favor an explanation having partial contributions from both T and F. We approximate the seismic anisotropy of the upper mantle with hexagonal symmetry, consistent with the assumption of two dimensionality of mantle flow. Our new tomographic technique uses a nonlinear inversion of P and slow S polarization delay times to simultaneously solve for coupled VP and VS heterogeneity throughout the model and for the magnitude of anisotropy within discrete domains. The domain dimensions and the dip of the anisotropy are fixed for each inversion but are varied in a grid search, obtaining the misfit of the models to the body wave delay data and to split times of vertically propagating S waves. The data misfit and the isotropic heterogeneity are sensitive to domain dimensions and dip of anisotropy. In a region centered beneath the SEPR the best average dip of the hexagonal symmetry axis is horizontal or dipping shallowly (<30??) west. Given the resolution of our data, a subaxial region characterized by vertically aligned symmetry axes may exist but is limited to be <80 km deep. We infer that the mantle flow beneath the SEPR is consistent with shallow asthenospheric return flow from the direction of the South Pacific superswell.

Bioinformatic Analysis Reveals Archaeal tRNATyr and tRNATrp Identities in Bacteria

PubMed Central

Mukai, Takahito; Reynolds, Noah M.; Crnković, Ana; Söll, Dieter

2017-01-01

The tRNA identity elements for some amino acids are distinct between the bacterial and archaeal domains. Searching in recent genomic and metagenomic sequence data, we found some candidate phyla radiation (CPR) bacteria with archaeal tRNA identity for Tyr-tRNA and Trp-tRNA synthesis. These bacteria possess genes for tyrosyl-tRNA synthetase (TyrRS) and tryptophanyl-tRNA synthetase (TrpRS) predicted to be derived from DPANN superphylum archaea, while the cognate tRNATyr and tRNATrp genes reveal bacterial or archaeal origins. We identified a trace of domain fusion and swapping in the archaeal-type TyrRS gene of a bacterial lineage, suggesting that CPR bacteria may have used this mechanism to create diverse proteins. Archaeal-type TrpRS of bacteria and a few TrpRS species of DPANN archaea represent a new phylogenetic clade (named TrpRS-A). The TrpRS-A open reading frames (ORFs) are always associated with another ORF (named ORF1) encoding an unknown protein without global sequence identity to any known protein. However, our protein structure prediction identified a putative HIGH-motif and KMSKS-motif as well as many α-helices that are characteristic of class I aminoacyl-tRNA synthetase (aaRS) homologs. These results provide another example of the diversity of molecular components that implement the genetic code and provide a clue to the early evolution of life and the genetic code. PMID:28230768

Endothermic decompositions of inorganic monocrystalline thin plates. I. Shape of polycrystalline product domains versus constraints and time

NASA Astrophysics Data System (ADS)

Bertrand, G.; Comperat, M.; Lallemant, M.; Watelle, G.

1980-03-01

Copper sulfate pentahydrate dehydration into trihydrate was investigated using monocrystalline platelets with varying crystallographic orientations. The morphological and kinetic features of the trihydrate domains were examined. Different shapes were observed: polygons (parallelograms, hexagons) and ellipses; their conditions of occurrence are reported in the (P, T) diagram. At first (for about 2 min), the ratio of the long to the short axes of elliptical domains changes with time; these subsequently develop homothetically and the rate ratio is then only pressure dependent. Temperature influence is inferred from that of pressure. Polygonal shapes are time dependent and result in ellipses. So far, no model can be put forward. Yet, qualitatively, the polygonal shape of a domain may be explained by the prevalence of the crystal arrangement and the elliptical shape by that of the solid tensorial properties. The influence of those factors might be modulated versus pressure, temperature, interface extent, and, thus, time.

Identification and Functional Characterization of G6PC2 Coding Variants Influencing Glycemic Traits Define an Effector Transcript at the G6PC2-ABCB11 Locus

PubMed Central

Mahajan, Anubha; Sim, Xueling; Ng, Hui Jin; Manning, Alisa; Rivas, Manuel A.; Highland, Heather M.; Locke, Adam E.; Grarup, Niels; Im, Hae Kyung; Cingolani, Pablo; Flannick, Jason; Fontanillas, Pierre; Fuchsberger, Christian; Gaulton, Kyle J.; Teslovich, Tanya M.; Rayner, N. William; Robertson, Neil R.; Beer, Nicola L.; Rundle, Jana K.; Bork-Jensen, Jette; Ladenvall, Claes; Blancher, Christine; Buck, David; Buck, Gemma; Burtt, Noël P.; Gabriel, Stacey; Gjesing, Anette P.; Groves, Christopher J.; Hollensted, Mette; Huyghe, Jeroen R.; Jackson, Anne U.; Jun, Goo; Justesen, Johanne Marie; Mangino, Massimo; Murphy, Jacquelyn; Neville, Matt; Onofrio, Robert; Small, Kerrin S.; Stringham, Heather M.; Syvänen, Ann-Christine; Trakalo, Joseph; Abecasis, Goncalo; Bell, Graeme I.; Blangero, John; Cox, Nancy J.; Duggirala, Ravindranath; Hanis, Craig L.; Seielstad, Mark; Wilson, James G.; Christensen, Cramer; Brandslund, Ivan; Rauramaa, Rainer; Surdulescu, Gabriela L.; Doney, Alex S. F.; Lannfelt, Lars; Linneberg, Allan; Isomaa, Bo; Tuomi, Tiinamaija; Jørgensen, Marit E.; Jørgensen, Torben; Kuusisto, Johanna; Uusitupa, Matti; Salomaa, Veikko; Spector, Timothy D.; Morris, Andrew D.; Palmer, Colin N. A.; Collins, Francis S.; Mohlke, Karen L.; Bergman, Richard N.; Ingelsson, Erik; Lind, Lars; Tuomilehto, Jaakko; Hansen, Torben; Watanabe, Richard M.; Prokopenko, Inga; Dupuis, Josee; Karpe, Fredrik; Groop, Leif; Laakso, Markku; Pedersen, Oluf; Florez, Jose C.; Morris, Andrew P.; Altshuler, David; Meigs, James B.; Boehnke, Michael; McCarthy, Mark I.; Lindgren, Cecilia M.; Gloyn, Anna L.

2015-01-01

Genome wide association studies (GWAS) for fasting glucose (FG) and insulin (FI) have identified common variant signals which explain 4.8% and 1.2% of trait variance, respectively. It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic variance. To test this, we analyzed exome-array data from up to 33,231 non-diabetic individuals of European ancestry. We found exome-wide significant (P<5×10-7) evidence for two loci not previously highlighted by common variant GWAS: GLP1R (p.Ala316Thr, minor allele frequency (MAF)=1.5%) influencing FG levels, and URB2 (p.Glu594Val, MAF = 0.1%) influencing FI levels. Coding variant associations can highlight potential effector genes at (non-coding) GWAS signals. At the G6PC2/ABCB11 locus, we identified multiple coding variants in G6PC2 (p.Val219Leu, p.His177Tyr, and p.Tyr207Ser) influencing FG levels, conditionally independent of each other and the non-coding GWAS signal. In vitro assays demonstrate that these associated coding alleles result in reduced protein abundance via proteasomal degradation, establishing G6PC2 as an effector gene at this locus. Reconciliation of single-variant associations and functional effects was only possible when haplotype phase was considered. In contrast to earlier reports suggesting that, paradoxically, glucose-raising alleles at this locus are protective against type 2 diabetes (T2D), the p.Val219Leu G6PC2 variant displayed a modest but directionally consistent association with T2D risk. Coding variant associations for glycemic traits in GWAS signals highlight PCSK1, RREB1, and ZHX3 as likely effector transcripts. These coding variant association signals do not have a major impact on the trait variance explained, but they do provide valuable biological insights. PMID:25625282

Identification and functional characterization of G6PC2 coding variants influencing glycemic traits define an effector transcript at the G6PC2-ABCB11 locus.

PubMed

Mahajan, Anubha; Sim, Xueling; Ng, Hui Jin; Manning, Alisa; Rivas, Manuel A; Highland, Heather M; Locke, Adam E; Grarup, Niels; Im, Hae Kyung; Cingolani, Pablo; Flannick, Jason; Fontanillas, Pierre; Fuchsberger, Christian; Gaulton, Kyle J; Teslovich, Tanya M; Rayner, N William; Robertson, Neil R; Beer, Nicola L; Rundle, Jana K; Bork-Jensen, Jette; Ladenvall, Claes; Blancher, Christine; Buck, David; Buck, Gemma; Burtt, Noël P; Gabriel, Stacey; Gjesing, Anette P; Groves, Christopher J; Hollensted, Mette; Huyghe, Jeroen R; Jackson, Anne U; Jun, Goo; Justesen, Johanne Marie; Mangino, Massimo; Murphy, Jacquelyn; Neville, Matt; Onofrio, Robert; Small, Kerrin S; Stringham, Heather M; Syvänen, Ann-Christine; Trakalo, Joseph; Abecasis, Goncalo; Bell, Graeme I; Blangero, John; Cox, Nancy J; Duggirala, Ravindranath; Hanis, Craig L; Seielstad, Mark; Wilson, James G; Christensen, Cramer; Brandslund, Ivan; Rauramaa, Rainer; Surdulescu, Gabriela L; Doney, Alex S F; Lannfelt, Lars; Linneberg, Allan; Isomaa, Bo; Tuomi, Tiinamaija; Jørgensen, Marit E; Jørgensen, Torben; Kuusisto, Johanna; Uusitupa, Matti; Salomaa, Veikko; Spector, Timothy D; Morris, Andrew D; Palmer, Colin N A; Collins, Francis S; Mohlke, Karen L; Bergman, Richard N; Ingelsson, Erik; Lind, Lars; Tuomilehto, Jaakko; Hansen, Torben; Watanabe, Richard M; Prokopenko, Inga; Dupuis, Josee; Karpe, Fredrik; Groop, Leif; Laakso, Markku; Pedersen, Oluf; Florez, Jose C; Morris, Andrew P; Altshuler, David; Meigs, James B; Boehnke, Michael; McCarthy, Mark I; Lindgren, Cecilia M; Gloyn, Anna L

2015-01-01

Genome wide association studies (GWAS) for fasting glucose (FG) and insulin (FI) have identified common variant signals which explain 4.8% and 1.2% of trait variance, respectively. It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic variance. To test this, we analyzed exome-array data from up to 33,231 non-diabetic individuals of European ancestry. We found exome-wide significant (P<5×10-7) evidence for two loci not previously highlighted by common variant GWAS: GLP1R (p.Ala316Thr, minor allele frequency (MAF)=1.5%) influencing FG levels, and URB2 (p.Glu594Val, MAF = 0.1%) influencing FI levels. Coding variant associations can highlight potential effector genes at (non-coding) GWAS signals. At the G6PC2/ABCB11 locus, we identified multiple coding variants in G6PC2 (p.Val219Leu, p.His177Tyr, and p.Tyr207Ser) influencing FG levels, conditionally independent of each other and the non-coding GWAS signal. In vitro assays demonstrate that these associated coding alleles result in reduced protein abundance via proteasomal degradation, establishing G6PC2 as an effector gene at this locus. Reconciliation of single-variant associations and functional effects was only possible when haplotype phase was considered. In contrast to earlier reports suggesting that, paradoxically, glucose-raising alleles at this locus are protective against type 2 diabetes (T2D), the p.Val219Leu G6PC2 variant displayed a modest but directionally consistent association with T2D risk. Coding variant associations for glycemic traits in GWAS signals highlight PCSK1, RREB1, and ZHX3 as likely effector transcripts. These coding variant association signals do not have a major impact on the trait variance explained, but they do provide valuable biological insights.

Development and Evaluation of a Monte Carlo Code System for Analysis of Ionization Chamber Responses,

DTIC Science & Technology

1987-07-01

ft. ft 3 ORNL/TM- 10196 INTERNAL DISTRIBUTION 1. F. S. Alsmiller 32. R. T. Santoro 2. R. G. Alsmiller, Jr. 33. M. S. Smith 3. D. E. Bartine 34. J. S...W. Armstrong, Science Applications, Inc., P.O. Box 2807, La Jolla, CA 92038. 57. Miguel Awschalom, National Accelerator Laboratory, P. 0. Box 500

Los1p, involved in yeast pre-tRNA splicing, positively regulates members of the SOL gene family.

PubMed

Shen, W C; Stanford, D R; Hopper, A K

1996-06-01

To understand the role of Los1p in pre-tRNA splicing, we sought los1 multicopy suppressors. We found SOL1 that suppresses both point and null LOS1 mutations. Since, when fused to the Ga14p DNA-binding domain, Los1p activates transcription, we tested whether Los1p regulates SOL1. We found that las1 mutants have depleted levels of SOL1 mRNA and Sol1p. Thus, LOS1 appears to positively regulate SOL1. SOL1 belongs to a multigene family with at least two additional members, SOL2 and SOL3. Sol proteins have extensive similarity to an unusual group of glucose-6-phosphate dehydrogenases. As the similarities are restricted to areas separate from the catalytic domain, these G6PDs may have more than one function. The SOL family appears to be unessential since cells with a triple disruption of all three SOL genes are viable. SOL gene disruptions negatively affect tRNA-mediated nonsense suppression and the severity increases with the number of mutant SOL genes. However, tRNA levels do not vary with either multicopy SOL genes or with SOL disruptions. Therefore, the Sol proteins affect tRNA expression/ function at steps other than transcription or splicing. We propose that LOS1 regulates gene products involved in tRNA expression/function as well as pre-tRNA splicing.

Methodology Investigation. Chamber Versus Environmental Deterioration Tests

DTIC Science & Technology

1979-01-01

instructions do not apply to the record copy (AR 340-18). UNCLASSIFIED S.CURITY CLASSIFICATION OF I HIS PAGE ("eiln Daoe FKnterpd) I PAGE READ INSTRUCTIONS...D 4 - from P. Pin F 0-0 Figure 14 ->TIL 302 TL3 * 10 I , C 1:1 FiL r 16. Diia0lcto i yt m c e- t 1C 234 -.>11- tandem. The binary coded decimal ...Mexico State University and/or the University I of Texas at El Paso will be contracted to assist in this investigation by performing detailed, time

Hybrid Raman/Brillouin-optical-time-domain-analysis-distributed optical fiber sensors based on cyclic pulse coding.

PubMed

Taki, M; Signorini, A; Oton, C J; Nannipieri, T; Di Pasquale, F

2013-10-15

We experimentally demonstrate the use of cyclic pulse coding for distributed strain and temperature measurements in hybrid Raman/Brillouin optical time-domain analysis (BOTDA) optical fiber sensors. The highly integrated proposed solution effectively addresses the strain/temperature cross-sensitivity issue affecting standard BOTDA sensors, allowing for simultaneous meter-scale strain and temperature measurements over 10 km of standard single mode fiber using a single narrowband laser source only.

A numerical code for the simulation of non-equilibrium chemically reacting flows on hybrid CPU-GPU clusters

NASA Astrophysics Data System (ADS)

Kudryavtsev, Alexey N.; Kashkovsky, Alexander V.; Borisov, Semyon P.; Shershnev, Anton A.

2017-10-01

In the present work a computer code RCFS for numerical simulation of chemically reacting compressible flows on hybrid CPU/GPU supercomputers is developed. It solves 3D unsteady Euler equations for multispecies chemically reacting flows in general curvilinear coordinates using shock-capturing TVD schemes. Time advancement is carried out using the explicit Runge-Kutta TVD schemes. Program implementation uses CUDA application programming interface to perform GPU computations. Data between GPUs is distributed via domain decomposition technique. The developed code is verified on the number of test cases including supersonic flow over a cylinder.

Implementation of Hydrodynamic Simulation Code in Shock Experiment Design for Alkali Metals

NASA Astrophysics Data System (ADS)

Coleman, A. L.; Briggs, R.; Gorman, M. G.; Ali, S.; Lazicki, A.; Swift, D. C.; Stubley, P. G.; McBride, E. E.; Collins, G.; Wark, J. S.; McMahon, M. I.

2017-10-01

Shock compression techniques enable the investigation of extreme P-T states. In order to probe off-Hugoniot regions of P-T space, target makeup and laser pulse parameters must be carefully designed. HYADES is a hydrodynamic simulation code which has been successfully utilised to simulate shock compression events and refine the experimental parameters required in order to explore new P-T states in alkali metals. Here we describe simulations and experiments on potassium, along with the techniques required to access off-Hugoniot states.

X-Ray Crystal Structure of the passenger domain of Plasmid encoded toxin(Pet), an Autotransporter Enterotoxin from enteroaggregative Escherichia coli (EAEC)

PubMed Central

Meza-Aguilar, J. Domingo; Fromme, Petra; Torres-Larios, Alfredo; Mendoza-Hernández, Guillermo; Hernandez-Chiñas, Ulises; Monteros, Roberto A. Arreguin-Espinosa de los; Campos, Carlos A. Eslava; Fromme, Raimund

2014-01-01

Autotransporters (ATs) represent a superfamily of proteins produced by a variety of pathogenic bacteria, which include the pathogenic groups of Escherichia coli (E. coli) associated with gastrointestinal and urinary tract infections. We present the first X-ray structure of the passenger domain from the Plasmid-encoded toxin (Pet) a 100 kDa protein at 2.3 Å resolution which is a cause of acute diarrhea in both developing and industrialized countries. Pet is a cytoskeleton-altering toxin that induces loss of actin stress fibers. While Pet (pdb code: 4OM9) shows only a sequence identity of 50 % compared to the closest related protein sequence, extracellular serine protease plasmid (EspP) the structural features of both proteins are conserved. A closer structural look reveals that Pet contains a β-pleaded sheet at the sequence region of residues 181-190, the corresponding structural domain in EspP consists of a coiled loop. Secondary, the Pet passenger domain features a more pronounced beta sheet between residues 135-143 compared to the structure of EspP. PMID:24530907

Nonequilibrium relaxations within the ground-state manifold in the antiferromagnetic Ising model on a triangular lattice.

PubMed

Kim, Eunhye; Lee, Sung Jong; Kim, Bongsoo

2007-02-01

We present an extensive Monte Carlo simulation study on the nonequilibrium kinetics of triangular antiferromagnetic Ising model within the ground state ensemble which consists of sectors, each of which is characterized by a unique value of the string density p through a dimer covering method. Building upon our recent work [Phys. Rev. E 68, 066127 (2003)] where we considered the nonequilibrium relaxation observed within the dominant sector with p=2/3, we here focus on the nonequilibrium kinetics within the minor sectors with p<2/3. The initial configurations are chosen as those in which the strings are straight and evenly distributed. In the minor sectors, we observe a characteristic spatial anisotropy in both equilibrium and nonequilibrium spatial correlations. We observe emergence of a critical relaxation region (in the spatial and temporal domain) which grows as p deviates from p=2/3. Spatial anisotropy appears in the equilibrium spatial correlation with the characteristic length scale xi(e,V)(p) diverging with vanishing string density as xi(e,V)(p) approximately p(-2) along the vertical direction, while along the horizontal direction the spatial length scale diverges as xi(e,H) approximately p(-1). Analytic forms for the anisotropic equilibrium correlation functions are given. We also find that the spin autocorrelation function A(t) shows a simple scaling behavior A(t)=A(t/tau(A)(p)), where the time scale tau(A)(p) shows a power-law divergence with vanishing p as tau(A)(p) approximately p(-phi) with phi approximately or equal to 4. These features can be understood in terms of random walk nature of the fluctuations of the strings within the typical separation between neighboring strings.

Spectroscopics database for warm Xenon and Iron in Astrophysics and Laboratory Astrophysics conditions

NASA Astrophysics Data System (ADS)

Busquet, Michel; Klapisch, Marcel; Bar-Shalom, Avi; Oreg, Josse

2010-11-01

The main contribution to spectral properties of astrophysics mixtures come often from Iron. On the other hand, in the so-called domain of ``Laboratory Astrophysics,'' where astrophysics phenomena are scaled down to the laboratory, Xenon (and Argon) are commonly used gases. At so called ``warm'' temperatures (T=5-50eV), L-shell Iron and M-shell Xenon present a very large number of spectral lines, originating from billions of levels. More often than not, Local Thermodynamical Equilibrium is assumed, leading to noticeable simplification of the computation. Nevertheless, complex and powerful atomic structure codes are required. We take benefit of powerful statistics and numerics, included in our atomic structure codes, STA[1] and HULLAC[2], to generate the required spectra. Recent improvements in both fields (statistics, numerics and convergence control) allow obtaining large databases (ro x T grid of > 200x200 points, and > 10000 frequencies) for temperature down to a few eV. We plan to port these improvements in the NLTE code SCROLL[3]. [1] A.Bar-Shalom, et al, Phys. Rev. A 40, 3183 (1989) [2] M.Busquet,et al, J.Phys. IV France 133, 973-975 (2006); A.Bar-Shalom, M.Klapisch, J.Oreg, J.Oreg, JQSRT 71, 169, (2001) [3] A.Bar-Shalom, et al, Phys. Rev. E 56, R70 (1997)

Preparation of Proper Immunogen by Cloning and Stable Expression of cDNA coding for Human Hematopoietic Stem Cell Marker CD34 in NIH-3T3 Mouse Fibroblast Cell Line

PubMed Central

Shafaghat, Farzaneh; Abbasi-Kenarsari, Hajar; Majidi, Jafar; Movassaghpour, Ali Akbar; Shanehbandi, Dariush; Kazemi, Tohid

2015-01-01

Purpose: Transmembrane CD34 glycoprotein is the most important marker for identification, isolation and enumeration of hematopoietic stem cells (HSCs). We aimed in this study to clone the cDNA coding for human CD34 from KG1a cell line and stably express in mouse fibroblast cell line NIH-3T3. Such artificial cell line could be useful as proper immunogen for production of mouse monoclonal antibodies. Methods: CD34 cDNA was cloned from KG1a cell line after total RNA extraction and cDNA synthesis. Pfu DNA polymerase-amplified specific band was ligated to pGEMT-easy TA-cloning vector and sub-cloned in pCMV6-Neo expression vector. After transfection of NIH-3T3 cells using 3 μg of recombinant construct and 6 μl of JetPEI transfection reagent, stable expression was obtained by selection of cells by G418 antibiotic and confirmed by surface flow cytometry. Results: 1158 bp specific band was aligned completely to reference sequence in NCBI database corresponding to long isoform of human CD34. Transient and stable expression of human CD34 on transfected NIH-3T3 mouse fibroblast cells was achieved (25% and 95%, respectively) as shown by flow cytometry. Conclusion: Cloning and stable expression of human CD34 cDNA was successfully performed and validated by standard flow cytometric analysis. Due to murine origin of NIH-3T3 cell line, CD34-expressing NIH-3T3 cells could be useful as immunogen in production of diagnostic monoclonal antibodies against human CD34. This approach could bypass the need for purification of recombinant proteins produced in eukaryotic expression systems. PMID:25789221

Impact of the implementation of the Infarction Code strategy in patients with acute myocardial infarction diagnosis in the Hospital de Cardiología of the Centro Médico Nacional Siglo XXI

PubMed

Sánchez, Gabriela Borrayo; Covarrubias, Héctor Álvarez; Rodríguez, Gilberto Pérez; Uribe, Efraín Arizmendi; Ramírez-Arias, Erick; Peralta, Martín Rosas; Dávila, Jesús Arriaga

2017-01-01

To evaluate the impact of the implementation of the Infarction Code strategy in patients with acute myocardial infarction diagnosis. Consecutive patients with ST-elevation acute myocardial infarction ≤12 hours of evolution, were included in the infarction code strategy, before (Group I) and after (Group II). Times of medical attention and major cardiovascular events during hospitalization were analyzed. 1227 patients were included, 919 men (75%) and 308 women (25%) with an average age of 62 ± 11 years. Among Group I and Group II, percutaneous coronary intervention reperfusion therapy changed (16.6% to 42.6%), fibrinolytic therapy (39.3% to 25%), and patients who did not receive any form of reperfusion therapy (44% to 32.6%; p < 0.0001). Times of medical attention decreased significantly (door-to-needle time decreased from 92 to 72 minutes, p = 0.004; door-to-balloon time decreased from 140 to 92 minutes, p < 0.0001). Kidney failure (24.6% vs. 17.9%; p = 0.006), major complications (35.3% to 29.3%), and death (21% vs. 12%; odds ratio: 0.52; 95% confidence interval: 0.38-0.71; p = 0.004). also decreased. The Infarction Code strategy improved treatment, times of medical attention and decreased complications and death in these patients.

Perception of educational environment among undergraduate students of health disciplines in an Iranian university

PubMed Central

Farajpour, Arezou; Raisolsadat, S. Mohammad Ali; S. Moghadam, Samaneh

2017-01-01

Objectives This paper seeks to determine the perception of Medical, Nursing and Midwifery students about their educational environment and compare their perceptions in terms of disciplines, demographic attributes and academic level. Methods In this cross-sectional study, Medical, Nursing and Midwifery students in Islamic Azad University, Mashhad, Iran, were selected using stratified random sampling method (N=378). They completed the standard Persian version of Dundee Ready Education Environment Measure (DREEM) questionnaire. Descriptive statistics, t-test and analysis of variance (ANOVA) were used to analyze data. Results The mean score of DREEM was 106 ± 24.6. The mean scores in five domains of DREEM questionnaire including students’ perception of learning, perception of teachers, scientific abilities, students’ perception of educational environment and students’ perception of social conditions were 23±8, 23.4±6, 18±5.5, 25.5±7.7 and 15.8±4, respectively. In the first four domains (p=0.000, F=27.35), (p=0.000, F=9.9), (p=0.000, F=18.5), (p=0.000, t=18.7) and for total scores (p=0.000, F=22.77), the three disciplines were significantly different. Also, there was a significant difference between mean total score (p=0.021, t=2.3) and scores of students’ perception of learning (p=0.008, t=2.65) and social conditions (p=0.022, t=2.3) with respect to gender. Conclusions According to these results, students tend to have a positive attitude towards their educational environment. The findings of this study are useful to identify areas in need of improvement by employing more specialized tools and planning for improvement.  PMID:28829330

Perception of educational environment among undergraduate students of health disciplines in an Iranian university.

PubMed

Farajpour, Arezou; Raisolsadat, S Mohammad Ali; S Moghadam, Samaneh; Mostafavian, Zahra

2017-08-18

This paper seeks to determine the perception of Medical, Nursing and Midwifery students about their educational environment and compare their perceptions in terms of disciplines, demographic attributes and academic level. In this cross-sectional study, Medical, Nursing and Midwifery students in Islamic Azad University, Mashhad, Iran, were selected using stratified random sampling method (N=378). They completed the standard Persian version of Dundee Ready Education Environment Measure (DREEM) questionnaire. Descriptive statistics, t-test and analysis of variance (ANOVA) were used to analyze data. The mean score of DREEM was 106 ± 24.6. The mean scores in five domains of DREEM questionnaire including students' perception of learning, perception of teachers, scientific abilities, students' perception of educational environment and students' perception of social conditions were 23±8, 23.4±6, 18±5.5, 25.5±7.7 and 15.8±4, respectively. In the first four domains (p=0.000, F=27.35), (p=0.000, F=9.9), (p=0.000, F=18.5), (p=0.000, t=18.7) and for total scores (p=0.000, F=22.77), the three disciplines were significantly different. Also, there was a significant difference between mean total score (p=0.021, t=2.3) and scores of students' perception of learning (p=0.008, t=2.65) and social conditions (p=0.022, t=2.3) with respect to gender. According to these results, students tend to have a positive attitude towards their educational environment. The findings of this study are useful to identify areas in need of improvement by employing more specialized tools and planning for improvement.

The structure of transcription termination factor Nrd1 reveals an original mode for GUAA recognition

PubMed Central

Franco-Echevarría, Elsa; González-Polo, Noelia; Zorrilla, Silvia; Martínez-Lumbreras, Santiago; Santiveri, Clara M.; Campos-Olivas, Ramón; Sánchez, Mar; Calvo, Olga

2017-01-01

Abstract Transcription termination of non-coding RNAs is regulated in yeast by a complex of three RNA binding proteins: Nrd1, Nab3 and Sen1. Nrd1 is central in this process by interacting with Rbp1 of RNA polymerase II, Trf4 of TRAMP and GUAA/G terminator sequences. We lack structural data for the last of these binding events. We determined the structures of Nrd1 RNA binding domain and its complexes with three GUAA-containing RNAs, characterized RNA binding energetics and tested rationally designed mutants in vivo. The Nrd1 structure shows an RRM domain fused with a second α/β domain that we name split domain (SD), because it is formed by two non-consecutive segments at each side of the RRM. The GUAA interacts with both domains and with a pocket of water molecules, trapped between the two stacking adenines and the SD. Comprehensive binding studies demonstrate for the first time that Nrd1 has a slight preference for GUAA over GUAG and genetic and functional studies suggest that Nrd1 RNA binding domain might play further roles in non-coding RNAs transcription termination. PMID:28973465

Time domain topology optimization of 3D nanophotonic devices

NASA Astrophysics Data System (ADS)

Elesin, Y.; Lazarov, B. S.; Jensen, J. S.; Sigmund, O.

2014-02-01

We present an efficient parallel topology optimization framework for design of large scale 3D nanophotonic devices. The code shows excellent scalability and is demonstrated for optimization of broadband frequency splitter, waveguide intersection, photonic crystal-based waveguide and nanowire-based waveguide. The obtained results are compared to simplified 2D studies and we demonstrate that 3D topology optimization may lead to significant performance improvements.

Real-time polymerase chain reaction assay for the rapid detection and characterization of chloroquine-resistant Plasmodium falciparum malaria in returned travelers.

PubMed

Farcas, Gabriella A; Soeller, Rainer; Zhong, Kathleen; Zahirieh, Alireza; Kain, Kevin C

2006-03-01

Imported drug-resistant malaria is a growing problem in industrialized countries. Rapid and accurate diagnosis is essential to prevent malaria-associated mortality in returned travelers. However, outside of a limited number of specialized centers, the microscopic diagnosis of malaria is slow, unreliable, and provides little information about drug resistance. Molecular diagnostics have the potential to overcome these limitations. We developed and evaluated a rapid, real-time polymerase chain reaction (PCR) assay to detect Plasmodium falciparum malaria and chloroquine (CQ)-resistance determinants in returned travelers who are febrile. A real-time PCR assay based on detection of the K76T mutation in PfCRT (K76T) of P. falciparum was developed on a LightCycler platform (Roche). The performance characteristics of the real-time assay were compared with those of the nested PCR-restriction fragment-length polymorphism (RFLP) and the sequence analyses of samples obtained from 200 febrile returned travelers, who included 125 infected with P. falciparum (48 of whom were infected CQ-susceptible [K76] and 77 of whom were CQ-resistant [T76] P. falciparum), 22 infected with Plasmodium vivax, 10 infected with Plasmodium ovale, 3 infected with Plasmodium malariae malaria, and 40 infected with other febrile syndromes. All patient samples were coded, and all analyses were performed blindly. The real-time PCR assay detected multiple pfcrt haplotypes associated with CQ resistance in geographically diverse malaria isolates acquired by travelers. Compared with nested-PCR RFLP (the reference standard), the real-time assay was 100% sensitive and 96.2% specific for detection of the P. falciparum K76T mutation. This assay is rapid, sensitive, and specific for the detection and characterization of CQ-resistant P. falciparum malaria in returned travelers. This assay is automated, standardized, and suitable for routine use in clinical diagnostic laboratories.

Regulation of DNA Replication Timing on Human Chromosome by a Cell-Type Specific DNA Binding Protein SATB1

PubMed Central

Oda, Masako; Kanoh, Yutaka; Watanabe, Yoshihisa; Masai, Hisao

2012-01-01

Background Replication timing of metazoan DNA during S-phase may be determined by many factors including chromosome structures, nuclear positioning, patterns of histone modifications, and transcriptional activity. It may be determined by Mb-domain structures, termed as “replication domains”, and recent findings indicate that replication timing is under developmental and cell type-specific regulation. Methodology/Principal Findings We examined replication timing on the human 5q23/31 3.5-Mb segment in T cells and non-T cells. We used two independent methods to determine replication timing. One is quantification of nascent replicating DNA in cell cycle-fractionated stage-specific S phase populations. The other is FISH analyses of replication foci. Although the locations of early- and late-replicating domains were common between the two cell lines, the timing transition region (TTR) between early and late domains were offset by 200-kb. We show that Special AT-rich sequence Binding protein 1 (SATB1), specifically expressed in T-cells, binds to the early domain immediately adjacent to TTR and delays the replication timing of the TTR. Measurement of the chromosome copy number along the TTR during synchronized S phase suggests that the fork movement may be slowed down by SATB1. Conclusions Our results reveal a novel role of SATB1 in cell type-specific regulation of replication timing along the chromosome. PMID:22879953

Thermodynamics of membrane insertion and refolding of the diphtheria toxin T-domain

PubMed Central

Vargas-Uribe, Mauricio; Rodnin, Mykola V.; Öjemalm, Karin; Holgado, Aurora; Kyrychenko, Alexander; Nilsson, IngMarie; Posokhov, Yevgen O.; Makhatadze, George; von Heijne, Gunnar; Ladokhin, Alexey S.

2014-01-01

The diphtheria toxin translocation (T) domain inserts into the endosomal membrane in response to the endosomal acidification and enables the delivery of the catalytic domain into the cell. The insertion pathway consists of a series of conformational changes that occur in solution and in the membrane and leads to the conversion of a water-soluble state into a transmembrane state. In this work, we utilize various biophysical techniques to characterize the insertion pathway from the thermodynamic perspective. Thermal and chemical unfolding measured by differential scanning calorimetry, circular dichroism and tryptophan fluorescence reveal that the free energy of unfolding of the T-domain at neutral and mildly acidic pH differ by 3–5 kcal/mol, depending on the experimental conditions. Fluorescence correlation spectroscopy measurements show that the free energy change from the membrane-competent state to the interfacial state is approximately −8 kcal/mol and is pH-independent, while that from the membrane-competent state to the transmembrane state ranges between −9.5 to −12 kcal/mol, depending on the membrane lipid composition and pH. Finally, the thermodynamics of transmembrane insertion of individual helices was tested using an in vitro assay that measures the translocon-assisted integration of test sequences into the microsomal membrane. These experiments suggest that even the most hydrophobic helix TH8 has only a small favorable free energy of insertion. The free energy for the insertion of the consensus insertion unit TH8-TH9 is slightly more favorable, yet less favorable than that measured for the entire protein, suggesting a cooperative effect for the membrane insertion of the helices of the T-domain. PMID:25281329

Conversion disorder in children and adolescents: a disorder of cognitive control.

PubMed

Kozlowska, Kasia; Palmer, Donna M; Brown, Kerri J; Scher, Stephen; Chudleigh, Catherine; Davies, Fiona; Williams, Leanne M

2015-03-01

To assess cognitive function in children and adolescents presenting with acute conversion symptoms. Fifty-seven participants aged 8.5-18 years (41 girls and 16 boys) with conversion symptoms and 57 age- and gender-matched healthy controls completed the IntegNeuro neurocognitive battery, an estimate of intelligence, and self-report measures of subjective emotional distress. Participants with conversion symptoms showed poorer performance within attention, executive function, and memory domains. Poorer performance was reflected in more errors on specific tests: Switching of Attention (t(79) = 2.17, p = .03); Verbal Interference (t(72) = 2.64, p = .01); Go/No-Go (t(73) = 2.20, p = .03); Memory Recall and Verbal Learning (interference errors for memory recall; t(61) = 3.13, p < .01); and short-delay recall (t(75) = 2.05, p < .01) and long-delay recall (t(62) = 2.24, p = .03). Poorer performance was also reflected in a reduced span of working memory on the Digit Span Test for both forward recall span (t(103) = -3.64, p < .001) and backward recall span (t(100) = -3.22, p < .01). There was no difference between participants and controls on IQ estimate (t(94) = -589, p = .56), and there was no correlation between cognitive function and perceived distress. Children and adolescents with acute conversion symptoms have a reduced capacity to manipulate and retain information, to block interfering information, and to inhibit responses, all of which are required for effective attention, executive function, and memory. © 2014 The British Psychological Society.

Implosive accretion and outbursts of active galactic nuclei

NASA Technical Reports Server (NTRS)

Lovelace, R. V. E.; Romanova, M. M.; Newman, W. I.

1994-01-01

A model and simulation code have been developed for time-dependent axisymmetric disk accretion onto a compact object including for the first time the influence of an ordered magnetic field. The accretion rate and radiative luminosity of the disk are naturally coupled to the rate of outflow of energy and angular momentum in magnetically driven (+/- z) winds. The magnetic field of the wind is treated in a phenomenological way suggested by self-consistent wind solutions. The radial accretion speed u(r, t) of the disk matter is shown to be the sum of the usual viscous contribution and a magnetic contribution proportional to r(exp 3/2)(B(sub p exp 2))/sigma, where B(sub p)(r,t) is the poloidal field threading the disk and sigma(r,t) is the disk's surface mass density. An enhancement or variation in B(sub p) at a large radial distance leads to the formation of a soliton-like structure in the disk density, temperature, and B-field which propagates implosively inward. The implosion gives a burst in the power output in winds or jets and a simultaneous burst in the disk radiation. The model is pertinent to the formation of discrete fast-moving components in jets observed by very long baseline interferometry. These components appear to originate at times of optical outbursts of the active galactic nucleus.

Draft Genome Sequence of Pseudomonas oceani DSM 100277T, a Deep-Sea Bacterium.

PubMed

García-Valdés, Elena; Gomila, Margarita; Mulet, Magdalena; Lalucat, Jorge

2018-04-12

Pseudomonas oceani DSM 100277 T was isolated from deep seawater in the Okinawa Trough at 1390 m. P. oceani belongs to the Pseudomonas pertucinogena group. Here, we report the draft genome sequence of P. oceani , which has an estimated size of 4.1 Mb and exhibits 3,790 coding sequences, with a G+C content of 59.94 mol%. Copyright © 2018 García-Valdés et al.

Mutations in nsP1 and PE2 are critical determinants of Ross River virus-induced musculoskeletal inflammatory disease in a mouse model

PubMed Central

Jupille, Henri J.; Oko, Lauren; Stoermer, Kristina A.; Heise, Mark T.; Mahalingam, Suresh; Gunn, Bronwyn M.; Morrison, Thomas E.

2010-01-01

The viral determinants of Alphavirus-induced rheumatic disease have not been elucidated. We identified an RRV strain (DC5692) which, in contrast to the T48 strain, does not induce musculoskeletal inflammation in a mouse model of RRV disease. Substitution of the RRV T48 strain nonstructural protein 1 (nsP1) coding sequence with that from strain DC5692 generated a virus that was attenuated in vivo despite similar viral loads in tissues. In contrast, substitution of the T48 PE2 coding region with the PE2 coding region from DC5692 resulted in attenuation in vivo and reduced viral loads in tissues. In gain of virulence experiments, substitution of the DC5692 strain nsP1 and PE2 coding regions with those from the T48 strain was sufficient to restore full virulence to the DC5692 strain. These findings indicate that determinants in both nsP1 and PE2 have critical and distinct roles in the pathogenesis of RRV-induced musculoskeletal inflammatory disease in mice. PMID:21131014

Combustor Computations for CO2-Neutral Aviation

NASA Technical Reports Server (NTRS)

Hendricks, Robert C.; Brankovic, Andreja; Ryder, Robert C.; Huber, Marcia

2011-01-01

Knowing the pure component C(sub p)(sup 0) or mixture C(sub p) (sup 0) as computed by a flexible code such as NIST-STRAPP or McBride-Gordon, one can, within reasonable accuracy, determine the thermophysical properties necessary to predict the combustion characteristics when there are no tabulated or computed data for those fluid mixtures 3or limited results for lower temperatures. (Note: C(sub p) (sup 0) is molar heat capacity at constant pressure.) The method can be used in the determination of synthetic and biological fuels and blends using the NIST code to compute the C(sub p) (sup 0) of the mixture. In this work, the values of the heat capacity were set at zero pressure, which provided the basis for integration to determine the required combustor properties from the injector to the combustor exit plane. The McBride-Gordon code was used to determine the heat capacity at zero pressure over a wide range of temperatures (room to 6,000 K). The selected fluids were Jet-A, 224TMP (octane), and C12. It was found that each heat capacity loci were form-similar. It was then determined that the results [near 400 to 3,000 K] could be represented to within acceptable engineering accuracy with the simplified equation C(sub p) (sup 0) = A/T + B, where A and B are fluid-dependent constants and T is temperature (K).

FDTD-ANT User Manual

NASA Technical Reports Server (NTRS)

Zimmerman, Martin L.

1995-01-01

This manual explains the theory and operation of the finite-difference time domain code FDTD-ANT developed by Analex Corporation at the NASA Lewis Research Center in Cleveland, Ohio. This code can be used for solving electromagnetic problems that are electrically small or medium (on the order of 1 to 50 cubic wavelengths). Calculated parameters include transmission line impedance, relative effective permittivity, antenna input impedance, and far-field patterns in both the time and frequency domains. The maximum problem size may be adjusted according to the computer used. This code has been run on the DEC VAX and 486 PC's and on workstations such as the Sun Sparc and the IBM RS/6000.

Parallelization of PANDA discrete ordinates code using spatial decomposition

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

Humbert, P.

2006-07-01

We present the parallel method, based on spatial domain decomposition, implemented in the 2D and 3D versions of the discrete Ordinates code PANDA. The spatial mesh is orthogonal and the spatial domain decomposition is Cartesian. For 3D problems a 3D Cartesian domain topology is created and the parallel method is based on a domain diagonal plane ordered sweep algorithm. The parallel efficiency of the method is improved by directions and octants pipelining. The implementation of the algorithm is straightforward using MPI blocking point to point communications. The efficiency of the method is illustrated by an application to the 3D-Ext C5G7more » benchmark of the OECD/NEA. (authors)« less

Research Prototype: Automated Analysis of Scientific and Engineering Semantics

NASA Technical Reports Server (NTRS)

Stewart, Mark E. M.; Follen, Greg (Technical Monitor)

2001-01-01

Physical and mathematical formulae and concepts are fundamental elements of scientific and engineering software. These classical equations and methods are time tested, universally accepted, and relatively unambiguous. The existence of this classical ontology suggests an ideal problem for automated comprehension. This problem is further motivated by the pervasive use of scientific code and high code development costs. To investigate code comprehension in this classical knowledge domain, a research prototype has been developed. The prototype incorporates scientific domain knowledge to recognize code properties (including units, physical, and mathematical quantity). Also, the procedure implements programming language semantics to propagate these properties through the code. This prototype's ability to elucidate code and detect errors will be demonstrated with state of the art scientific codes.

Return probability after a quench from a domain wall initial state in the spin-1/2 XXZ chain

NASA Astrophysics Data System (ADS)

Stéphan, Jean-Marie

2017-10-01

We study the return probability and its imaginary (τ) time continuation after a quench from a domain wall initial state in the XXZ spin chain, focusing mainly on the region with anisotropy \\vert Δ\\vert < 1 . We establish exact Fredholm determinant formulas for those, by exploiting a connection to the six-vertex model with domain wall boundary conditions. In imaginary time, we find the expected scaling for a partition function of a statistical mechanical model of area proportional to τ2 , which reflects the fact that the model exhibits the limit shape phenomenon. In real time, we observe that in the region \\vert Δ\\vert <1 the decay for long time t is nowhere continuous as a function of anisotropy: it is Gaussian at roots of unity and exponential otherwise. We also determine that the front moves as x_f(t)=t\\sqrt{1-Δ^2} , by the analytic continuation of known arctic curves in the six-vertex model. Exactly at \\vert Δ\\vert =1 , we find the return probability decays as e-\\zeta(3/2) \\sqrt{t/π}t1/2O(1) . It is argued that this result provides an upper bound on spin transport. In particular, it suggests that transport should be diffusive at the isotropic point for this quench.

Simulation of nonlinear propagation of biomedical ultrasound using PZFlex and the KZK Texas code

NASA Astrophysics Data System (ADS)

Qiao, Shan; Jackson, Edward; Coussios, Constantin-C.; Cleveland, Robin

2015-10-01

In biomedical ultrasound nonlinear acoustics can be important in both diagnostic and therapeutic applications and robust simulations tools are needed in the design process but also for day-to-day use such as treatment planning. For most biomedical application the ultrasound sources generate focused sound beams of finite amplitude. The KZK equation is a common model as it accounts for nonlinearity, absorption and paraxial diffraction and there are a number of solvers available, primarily developed by research groups. We compare the predictions of the KZK Texas code (a finite-difference time-domain algorithm) to an FEM-based commercial software, PZFlex. PZFlex solves the continuity equation and momentum conservation equation with a correction for nonlinearity in the equation of state incorporated using an incrementally linear, 2nd order accurate, explicit algorithm in time domain. Nonlinear ultrasound beams from two transducers driven at 1 MHz and 3.3 MHz respectively were simulated by both the KZK Texas code and PZFlex, and the pressure field was also measured by a fibre-optic hydrophone to validate the models. Further simulations were carried out a wide range of frequencies. The comparisons showed good agreement for the fundamental frequency for PZFlex, the KZK Texas code and the experiments. For the harmonic components, the KZK Texas code was in good agreement with measurements but PZFlex underestimated the amplitude: 32% for the 2nd harmonic and 66% for the 3rd harmonic. The underestimation of harmonics by PZFlex was more significant when the fundamental frequency increased. Furthermore non-physical oscillations in the axial profile of harmonics occurred in the PZFlex results when the amplitudes were relatively low. These results suggest that careful benchmarking of nonlinear simulations is important.

Simulation of nonlinear propagation of biomedical ultrasound using PZFlex and the KZK Texas code

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

Qiao, Shan, E-mail: shan.qiao@eng.ox.ac.uk; Jackson, Edward; Coussios, Constantin-C

In biomedical ultrasound nonlinear acoustics can be important in both diagnostic and therapeutic applications and robust simulations tools are needed in the design process but also for day-to-day use such as treatment planning. For most biomedical application the ultrasound sources generate focused sound beams of finite amplitude. The KZK equation is a common model as it accounts for nonlinearity, absorption and paraxial diffraction and there are a number of solvers available, primarily developed by research groups. We compare the predictions of the KZK Texas code (a finite-difference time-domain algorithm) to an FEM-based commercial software, PZFlex. PZFlex solves the continuity equationmore » and momentum conservation equation with a correction for nonlinearity in the equation of state incorporated using an incrementally linear, 2nd order accurate, explicit algorithm in time domain. Nonlinear ultrasound beams from two transducers driven at 1 MHz and 3.3 MHz respectively were simulated by both the KZK Texas code and PZFlex, and the pressure field was also measured by a fibre-optic hydrophone to validate the models. Further simulations were carried out a wide range of frequencies. The comparisons showed good agreement for the fundamental frequency for PZFlex, the KZK Texas code and the experiments. For the harmonic components, the KZK Texas code was in good agreement with measurements but PZFlex underestimated the amplitude: 32% for the 2nd harmonic and 66% for the 3rd harmonic. The underestimation of harmonics by PZFlex was more significant when the fundamental frequency increased. Furthermore non-physical oscillations in the axial profile of harmonics occurred in the PZFlex results when the amplitudes were relatively low. These results suggest that careful benchmarking of nonlinear simulations is important.« less

A Smad action turnover switch operated by WW domain readers of a phosphoserine code

PubMed Central

Aragón, Eric; Goerner, Nina; Zaromytidou, Alexia-Ileana; Xi, Qiaoran; Escobedo, Albert; Massagué, Joan; Macias, Maria J.

2011-01-01

When directed to the nucleus by TGF-β or BMP signals, Smad proteins undergo cyclin-dependent kinase 8/9 (CDK8/9) and glycogen synthase kinase-3 (GSK3) phosphorylations that mediate the binding of YAP and Pin1 for transcriptional action, and of ubiquitin ligases Smurf1 and Nedd4L for Smad destruction. Here we demonstrate that there is an order of events—Smad activation first and destruction later—and that it is controlled by a switch in the recognition of Smad phosphoserines by WW domains in their binding partners. In the BMP pathway, Smad1 phosphorylation by CDK8/9 creates binding sites for the WW domains of YAP, and subsequent phosphorylation by GSK3 switches off YAP binding and adds binding sites for Smurf1 WW domains. Similarly, in the TGF-β pathway, Smad3 phosphorylation by CDK8/9 creates binding sites for Pin1 and GSK3, then adds sites to enhance Nedd4L binding. Thus, a Smad phosphoserine code and a set of WW domain code readers provide an efficient solution to the problem of coupling TGF-β signal delivery to turnover of the Smad signal transducers. PMID:21685363

The first case of NSHL by direct impression on EYA1 gene and identification of one novel mutation in MYO7A in the Iranian families.

PubMed

Razmara, Ehsan; Bitarafan, Fatemeh; Esmaeilzadeh-Gharehdaghi, Elika; Almadani, Navid; Garshasbi, Masoud

2018-03-01

Targeted next-generation sequencing (NGS) provides a consequential opportunity to elucidate genetic factors in known diseases, particularly in profoundly heterogeneous disorders such as non-syndromic hearing loss (NSHL). Hearing impairments could be classified into syndromic and non-syndromic types. This study intended to assess the significance of mutations in these genes to the autosomal recessive/dominant non-syndromic genetic load among Iranian families. Two families were involved in this research and two patients were examined by targeted next-generation sequencing. Here we report two novel mutations in the MYO7A and EYA1 genes in two patients detected by targeted NGS. They were confirmed by Sanger sequencing and quantitative real-time PCR techniques. In this investigation, we identified a novel mutation in MYO7A , c.3751G>C, p.A1251P, along with another previously identified mutation (c.1708C>T) in one of the cases. This mutation is located in the MYTH4 protein domain which is a pivotal domain for the myosin function. Another finding in this research was a novel de-novo deletion which deletes the entire EYA1 coding region (EX1-18 DEL). Mutations in EYA1 gene have been found in branchiootorenal (BOR) syndrome. Interestingly the patient with EYA1 deletion did not show any other additional clinical implications apart from HL. This finding might argue for the sole involvement of EYA1 function in the mechanism of hearing. This investigation exhibited that the novel mutations in MYO7A , c.3751G>C, p.A1251P, and EYA1 , EX1-18 DEL, were associated with NSHL. Our research increased the mutation spectrum of hearing loss in the Iranian population.

Multiple origins of resistance-conferring mutations in Plasmodium vivax dihydrofolate reductase

PubMed Central

Hawkins, Vivian N; Auliff, Alyson; Prajapati, Surendra Kumar; Rungsihirunrat, Kanchana; Hapuarachchi, Hapuarachchige C; Maestre, Amanda; O'Neil, Michael T; Cheng, Qin; Joshi, Hema; Na-Bangchang, Kesara; Sibley, Carol Hopkins

2008-01-01

Background In order to maximize the useful therapeutic life of antimalarial drugs, it is crucial to understand the mechanisms by which parasites resistant to antimalarial drugs are selected and spread in natural populations. Recent work has demonstrated that pyrimethamine-resistance conferring mutations in Plasmodium falciparum dihydrofolate reductase (dhfr) have arisen rarely de novo, but spread widely in Asia and Africa. The origin and spread of mutations in Plasmodium vivax dhfr were assessed by constructing haplotypes based on sequencing dhfr and its flanking regions. Methods The P. vivax dhfr coding region, 792 bp upstream and 683 bp downstream were amplified and sequenced from 137 contemporary patient isolates from Colombia, India, Indonesia, Papua New Guinea, Sri Lanka, Thailand, and Vanuatu. A repeat motif located 2.6 kb upstream of dhfr was also sequenced from 75 of 137 patient isolates, and mutational relationships among the haplotypes were visualized using the programme Network. Results Synonymous and non-synonymous single nucleotide polymorphisms (SNPs) within the dhfr coding region were identified, as was the well-documented in-frame insertion/deletion (indel). SNPs were also identified upstream and downstream of dhfr, with an indel and a highly polymorphic repeat region identified upstream of dhfr. The regions flanking dhfr were highly variable. The double mutant (58R/117N) dhfr allele has evolved from several origins, because the 58R is encoded by at least 3 different codons. The triple (58R/61M/117T) and quadruple (57L/61M/117T/173F, 57I/58R/61M/117T and 57L/58R/61M/117T) mutant alleles had at least three independent origins in Thailand, Indonesia, and Papua New Guinea/Vanuatu. Conclusion It was found that the P. vivax dhfr coding region and its flanking intergenic regions are highly polymorphic and that mutations in P. vivax dhfr that confer antifolate resistance have arisen several times in the Asian region. This contrasts sharply with the selective sweep of rare antifolate resistant alleles observed in the P. falciparum populations in Asia and Africa. The finding of multiple origins of resistance-conferring mutations has important implications for drug policy. PMID:18442404

Multiple origins of resistance-conferring mutations in Plasmodium vivax dihydrofolate reductase.

PubMed

Hawkins, Vivian N; Auliff, Alyson; Prajapati, Surendra Kumar; Rungsihirunrat, Kanchana; Hapuarachchi, Hapuarachchige C; Maestre, Amanda; O'Neil, Michael T; Cheng, Qin; Joshi, Hema; Na-Bangchang, Kesara; Sibley, Carol Hopkins

2008-04-28

In order to maximize the useful therapeutic life of antimalarial drugs, it is crucial to understand the mechanisms by which parasites resistant to antimalarial drugs are selected and spread in natural populations. Recent work has demonstrated that pyrimethamine-resistance conferring mutations in Plasmodium falciparum dihydrofolate reductase (dhfr) have arisen rarely de novo, but spread widely in Asia and Africa. The origin and spread of mutations in Plasmodium vivax dhfr were assessed by constructing haplotypes based on sequencing dhfr and its flanking regions. The P. vivax dhfr coding region, 792 bp upstream and 683 bp downstream were amplified and sequenced from 137 contemporary patient isolates from Colombia, India, Indonesia, Papua New Guinea, Sri Lanka, Thailand, and Vanuatu. A repeat motif located 2.6 kb upstream of dhfr was also sequenced from 75 of 137 patient isolates, and mutational relationships among the haplotypes were visualized using the programme Network. Synonymous and non-synonymous single nucleotide polymorphisms (SNPs) within the dhfr coding region were identified, as was the well-documented in-frame insertion/deletion (indel). SNPs were also identified upstream and downstream of dhfr, with an indel and a highly polymorphic repeat region identified upstream of dhfr. The regions flanking dhfr were highly variable. The double mutant (58R/117N) dhfr allele has evolved from several origins, because the 58R is encoded by at least 3 different codons. The triple (58R/61M/117T) and quadruple (57L/61M/117T/173F, 57I/58R/61M/117T and 57L/58R/61M/117T) mutant alleles had at least three independent origins in Thailand, Indonesia, and Papua New Guinea/Vanuatu. It was found that the P. vivax dhfr coding region and its flanking intergenic regions are highly polymorphic and that mutations in P. vivax dhfr that confer antifolate resistance have arisen several times in the Asian region. This contrasts sharply with the selective sweep of rare antifolate resistant alleles observed in the P. falciparum populations in Asia and Africa. The finding of multiple origins of resistance-conferring mutations has important implications for drug policy.

Atmospheric Transmittance/Radiance: Computer Code LOWTRAN 4

DTIC Science & Technology

1978-02-28

LOWE 74~ A 4L p~i � l A 41 C MI=CbgASEAVEQ ALT ITUDE ( kM) LUO ?F bO A 43- C, HT:’=PLPCE At I I 1( 0KI ( KIM) LOWE iTA A 4.3 C ANGLE: 7ENUNH ANriE AT...ANMr, td 400 21’ , 5P9 1- SPHI/P" ANG4 2410 C 2 191 0:05 151RPM I) ANCL .󈧮 C’ 9 c GO To IANGL 430 2301 5 OtýT 1 -:BEI t ANGI27440O 薷 L *- ANGI

Computational electronics and electromagnetics

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

Shang, C. C.

The Computational Electronics and Electromagnetics thrust area at Lawrence Livermore National Laboratory serves as the focal point for engineering R&D activities for developing computer-based design, analysis, and tools for theory. Key representative applications include design of particle accelerator cells and beamline components; engineering analysis and design of high-power components, photonics, and optoelectronics circuit design; EMI susceptibility analysis; and antenna synthesis. The FY-96 technology-base effort focused code development on (1) accelerator design codes; (2) 3-D massively parallel, object-oriented time-domain EM codes; (3) material models; (4) coupling and application of engineering tools for analysis and design of high-power components; (5) 3-D spectral-domainmore » CEM tools; and (6) enhancement of laser drilling codes. Joint efforts with the Power Conversion Technologies thrust area include development of antenna systems for compact, high-performance radar, in addition to novel, compact Marx generators. 18 refs., 25 figs., 1 tab.« less

TacSat-4 COMMx, Advanced SATCOM Experiment

DTIC Science & Technology

2009-01-01

Schein, M. T. Marley, C. T. Apland, R. E. Lee, B. D . Williams, E. D . Schaefer, S. R. Vernon, P . D . Schwartz , B. L. Kantsiper, E. J. Finnegan;The...Lee, B. D . Williams, E. D . Schaefer, P . D . Schwartz, R. Denissen, B. Kantsiper, E. J. Finnegan; The Johns Hopkins University Applied Physics...Mission Ops Lead, NRL Code 8233 Bob Kuzma, TacSat-4 Payload Controller, NRL Code 8242 Bob Skalitzky, TacSat-4 Power Systems, NRL Code 8244 Doug Bentz

Mutational spectrum of Xeroderma pigmentosum group A in Egyptian patients.

PubMed

Amr, Khalda; Messaoud, Olfa; El Darouti, Mohamad; Abdelhak, Sonia; El-Kamah, Ghada

2014-01-01

Xeroderma pigmentosum (XP) is a rare autosomal recessive hereditary disease characterized by hyperphotosensitivity, DNA repair defects and a predisposition to skin cancers. The most frequently occurring type worldwide is the XP group A (XPA). There is a close relationship between the clinical features that ranged from severe to mild form and the mutational site in XPA gene. The aim of this study is to carry out the mutational analysis in Egyptian patients with XP-A. This study was carried out on four unrelated Egyptian XP-A families. Clinical features were examined and direct sequencing of the coding region of XPA gene was performed in patients and their parents. Direct sequencing of the whole coding region of the XPA gene revealed the identification of two homozygous nonsense mutations: (c.553C >T; p.(Gln185)) and (c.331G>T; p.(Glu111)), which create premature, stop codon and a homodeletion (c.374delC: p.Thr125Ilefs 15) that leads to frameshift and premature translation termination. We report the identification of one novel XPA gene mutation and two known mutations in four unrelated Egyptian families with Xermoderma pigmentosum. All explored patients presented severe neurological abnormalities and have mutations located in the DNA binding domain. This report gives insight on the mutation spectrum of XP-A in Egypt. This would provide a valuable tool for early diagnosis of this severe disease. © 2013 Elsevier B.V. All rights reserved.

A Computer Model Predicting the Thermal Response to Microwave Radiation

DTIC Science & Technology

1982-12-01

While each of these represents the result of a triple integration, the total running time is still only between 3 and 4 main on an IBM 360 for K...T/Tp]Tp + (i-1)T p (3.4.9) M(TN) min(([T-[T/Tp] iTp )/T ],Np) (3.4.10) t(TNTT)= MTN) +rTT 1T (3.4.11) t(,ppPT, ’(,p )T L"’PJ-’P x =x(NJ~1~T~ = 0 if...TRM - SRM1)/TRM 101 .: S . .-. . . . . . . . .. . . . . 4.6. Program Size and Running Time The program requires 252K on the ’GO’ step for an IBM 360

SLP-76 sterile α motif (SAM) and individual H5 α helix mediate oligomer formation for microclusters and T-cell activation.

PubMed

Liu, Hebin; Thaker, Youg Raj; Stagg, Loren; Schneider, Helga; Ladbury, John E; Rudd, Christopher E

2013-10-11

Despite the importance of the immune adaptor SLP-76 in T-cell immunity, it has been unclear whether SLP-76 directly self-associates to form higher order oligomers for T-cell activation. In this study, we show that SLP-76 self-associates in response to T-cell receptor ligation as mediated by the N-terminal sterile α motif (SAM) domain. SLP-76 co-precipitated alternately tagged SLP-76 in response to anti-CD3 ligation. Dynamic light scattering and fluorescent microscale thermophoresis of the isolated SAM domain (residues 1-78) revealed evidence of dimers and tetramers. Consistently, deletion of the SAM region eliminated SLP-76 co-precipitation of itself, concurrent with a loss of microcluster formation, nuclear factor of activated T-cells (NFAT) transcription, and interleukin-2 production in Jurkat or primary T-cells. Furthermore, the H5 α helix within the SAM domain contributed to self-association. Retention of H5 in the absence of H1-4 sufficed to support SLP-76 self-association with smaller microclusters that nevertheless enhanced anti-CD3-driven AP1/NFAT transcription and IL-2 production. By contrast, deletion of the H5 α helix impaired self-association and anti-CD3 induced AP1/NFAT transcription. Our data identified for the first time a role for the SAM domain in mediating SLP-76 self-association for T-cell function.

SLP-76 Sterile α Motif (SAM) and Individual H5 α Helix Mediate Oligomer Formation for Microclusters and T-cell Activation*

PubMed Central

Liu, Hebin; Thaker, Youg Raj; Stagg, Loren; Schneider, Helga; Ladbury, John E.; Rudd, Christopher E.

2013-01-01

Despite the importance of the immune adaptor SLP-76 in T-cell immunity, it has been unclear whether SLP-76 directly self-associates to form higher order oligomers for T-cell activation. In this study, we show that SLP-76 self-associates in response to T-cell receptor ligation as mediated by the N-terminal sterile α motif (SAM) domain. SLP-76 co-precipitated alternately tagged SLP-76 in response to anti-CD3 ligation. Dynamic light scattering and fluorescent microscale thermophoresis of the isolated SAM domain (residues 1–78) revealed evidence of dimers and tetramers. Consistently, deletion of the SAM region eliminated SLP-76 co-precipitation of itself, concurrent with a loss of microcluster formation, nuclear factor of activated T-cells (NFAT) transcription, and interleukin-2 production in Jurkat or primary T-cells. Furthermore, the H5 α helix within the SAM domain contributed to self-association. Retention of H5 in the absence of H1–4 sufficed to support SLP-76 self-association with smaller microclusters that nevertheless enhanced anti-CD3-driven AP1/NFAT transcription and IL-2 production. By contrast, deletion of the H5 α helix impaired self-association and anti-CD3 induced AP1/NFAT transcription. Our data identified for the first time a role for the SAM domain in mediating SLP-76 self-association for T-cell function. PMID:23935094

Balanced PIN-TIA photoreceiver with integrated 3 dB fiber coupler for distributed fiber optic sensors

NASA Astrophysics Data System (ADS)

Datta, Shubhashish; Rajagopalan, Sruti; Lemke, Shaun; Joshi, Abhay

2014-06-01

We report a balanced PIN-TIA photoreceiver integrated with a 3 dB fiber coupler for distributed fiber optic sensors. This detector demonstrates -3 dB bandwidth >15 GHz and coupled conversion gain >65 V/W per photodiode through either input port of the 3 dB coupler, and can be operated at local oscillator power of +17 dBm. The combined common mode rejection of the balanced photoreceiver and the integrated 3 dB coupler is >20 dB. We also present measurement results with various optical stimuli, namely impulses, sinusoids, and pseudo-random sequences, which are relevant for time domain reflectometry, frequency domain reflectometry, and code correlation sensors, respectively.

Residual oxygen time model for oxygen partial pressure near 130 kPa (1.3 atm).

PubMed

Shykoff, Barbara E

2015-01-01

A two-part residual oxygen time model predicts the probability of detectible pulmonary oxygen toxicity P(P[O2tox]) after dives with oxygen partial pressure (PO2) approximately 130 kPa, and provides a tool to plan dive series with selected risk of P[O2tox]. Data suggest that pulmonary oxygen injury at this PO2 is additive between dives. Recovery begins after a delay and continues during any following dive. A logistic relation expresses P(P[O2tox]) as a function of dive duration (T(dur)) [hours]: P(P[O2tox]) = 100/[1+exp (3.586-0.49 x T(dur))] This expression maps T(dur) to P(P[O2tox]) or, in the linear mid-portion of the curve, P(P[O2tox]) usefully to T(dur). For multiple dives or during recovery, it maps to an equivalent dive duration, T(eq). T(eq) was found after second dives of duration T(dur 2). Residual time from the first dive t(r) = T(eq) - T(dur2). With known t(r), t and T(dur) a recovery model was fitted. t(r) = T(dur) x exp [-k x((t-5)/T(dur)2], where t = t - 5 hours, k = 0.149 for resting, and 0.047 for exercising divers, and t represents time after surfacing. The fits were assessed for 1,352 man-dives. Standard deviations of the residuals were 8.5% and 18.3% probability for resting or exercise dives, respectively.

New Reduced Two-Time Step Method for Calculating Combustion and Emission Rates of Jet-A and Methane Fuel With and Without Water Injection

NASA Technical Reports Server (NTRS)

Molnar, Melissa; Marek, C. John

2004-01-01

A simplified kinetic scheme for Jet-A, and methane fuels with water injection was developed to be used in numerical combustion codes, such as the National Combustor Code (NCC) or even simple FORTRAN codes that are being developed at Glenn. The two time step method is either an initial time averaged value (step one) or an instantaneous value (step two). The switch is based on the water concentration in moles/cc of 1x10(exp -20). The results presented here results in a correlation that gives the chemical kinetic time as two separate functions. This two step method is used as opposed to a one step time averaged method previously developed to determine the chemical kinetic time with increased accuracy. The first time averaged step is used at the initial times for smaller water concentrations. This gives the average chemical kinetic time as a function of initial overall fuel air ratio, initial water to fuel mass ratio, temperature, and pressure. The second instantaneous step, to be used with higher water concentrations, gives the chemical kinetic time as a function of instantaneous fuel and water mole concentration, pressure and temperature (T4). The simple correlations would then be compared to the turbulent mixing times to determine the limiting properties of the reaction. The NASA Glenn GLSENS kinetics code calculates the reaction rates and rate constants for each species in a kinetic scheme for finite kinetic rates. These reaction rates were then used to calculate the necessary chemical kinetic times. Chemical kinetic time equations for fuel, carbon monoxide and NOx were obtained for Jet-A fuel and methane with and without water injection to water mass loadings of 2/1 water to fuel. A similar correlation was also developed using data from NASA's Chemical Equilibrium Applications (CEA) code to determine the equilibrium concentrations of carbon monoxide and nitrogen oxide as functions of overall equivalence ratio, water to fuel mass ratio, pressure and temperature (T3). The temperature of the gas entering the turbine (T4) was also correlated as a function of the initial combustor temperature (T3), equivalence ratio, water to fuel mass ratio, and pressure.

Interaction between the AAA ATPase p97/VCP and a concealed UBX domain in the copper transporter ATP7A is associated with motor neuron degeneration.

PubMed

Yi, Ling; Kaler, Stephen G

2018-05-18

The copper-transporting ATPase ATP7A contains eight transmembrane domains and is required for normal human copper homeostasis. Mutations in the ATP7A gene may lead to infantile-onset cerebral degeneration (Menkes disease); occipital horn syndrome (OHS), a related but much milder illness; or an adult-onset isolated distal motor neuropathy. The ATP7A missense mutation T994I is located in the sixth transmembrane domain of ATP7A, represents one of the variants associated with the latter phenotype, and is associated with an abnormal interaction with p97/valosin-containing protein (VCP), a hexameric AAA ATPase (ATPase associated with diverse cellular activities) with multiple biological functions. In this study, we further characterized this interaction and discovered a concealed UBX domain in the third lumenal loop of ATP7A, between its fifth and sixth transmembrane domains. We show that the T994I substitution results in conformational exposure of the UBX domain, which then binds the N-terminal domain of p97/VCP. We also show that this abnormal interaction occurs at or near the cell plasma membrane. The UBX domain has a conserved hydrophobic FP (Phe-Pro) motif, and substitution with di-alanine abrogated the interaction and restored the proper intracellular localization of ATP7A in the trans -Golgi network. Using protein MS, we identified potential coordinating components of the ATP7A T994I -p97 complex, including NSFL1 cofactor (NSF1C or p47) that may be relevant to the pathophysiology and clinical effects associated with ATP7A T994I Our study represents the first report of p97/VCP binding to a UBX domain that is not normally exposed, resulting in an aberrant protein-protein interaction leading to motor neuron degeneration.

Crystal Structure and Oligomeric State of the RetS Signaling Kinase Sensory Domain

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

Jing, X.; Jaw, J; Robinson, H

2010-01-01

The opportunistic pathogen Pseudomonas aeruginosa may cause both acute and chronic-persistent infections in predisposed individuals. Acute infections require the presence of a functional type III secretion system (T3SS), whereas chronic P. aeruginosa infections are characterized by the formation of drug-resistant biofilms. The T3SS and biofilm formation are reciprocally regulated by the signaling kinases LadS, RetS, and GacS. RetS downregulates biofilm formation and upregulates expression of the T3SS through a unique mechanism. RetS forms a heterodimeric complex with GacS and thus prevents GacS autophosphorylation and downstream signaling. The signals that regulate RetS are not known but RetS possesses a distinctive periplasmicmore » sensor domain that is believed to serve as receptor for the regulatory ligand. We have determined the crystal structure of the RetS sensory domain at 2.0 {angstrom} resolution. The structure closely resembles those of carbohydrate binding modules of other proteins, suggesting that the elusive ligands are likely carbohydrate moieties. In addition to the conserved beta-sandwich structure, the sensory domain features two alpha helices which create a unique surface topology. Protein-protein crosslinking and fluorescence energy transfer experiments also revealed that the sensory domain dimerizes with a dissociation constant of K{sub d} = 580 {+-} 50 nM, a result with interesting implications for our understanding of the underlying signaling mechanism.« less

ESAS Deliverable PS 1.1.2.3: Customer Survey on Code Generations in Safety-Critical Applications

NASA Technical Reports Server (NTRS)

Schumann, Johann; Denney, Ewen

2006-01-01

Automated code generators (ACG) are tools that convert a (higher-level) model of a software (sub-)system into executable code without the necessity for a developer to actually implement the code. Although both commercially supported and in-house tools have been used in many industrial applications, little data exists on how these tools are used in safety-critical domains (e.g., spacecraft, aircraft, automotive, nuclear). The aims of the survey, therefore, were threefold: 1) to determine if code generation is primarily used as a tool for prototyping, including design exploration and simulation, or for fiight/production code; 2) to determine the verification issues with code generators relating, in particular, to qualification and certification in safety-critical domains; and 3) to determine perceived gaps in functionality of existing tools.

Anisotropic transport properties of the two-dimensional electron gas in ordered-disordered GaInP2 homojunctions: The structure of ordered domains

NASA Astrophysics Data System (ADS)

Driessen, F. A. J. M.; Bauhuis, G. J.; Hageman, P. R.; van Geelen, A.; Giling, L. J.

1994-12-01

The modulation-doped ordered-GaInP2/disordered-GaInP2 homojunction is presented. Capacitance-voltage (CV) profiling techniques, temperature-dependent Hall and resistivity measurements, cross-sectional transverse electron micrographs (TEM), and high-field magnetotransport have been used to characterize this structure grown by metal-organic vapor-phase epitaxy. The CV measurements showed a narrow profile at the homointerface with an order of magnitude reduction in carrier density within 3 nm. Typical two-dimensional behavior was observed from Hall data showing sheet carrier densities as high as 3.6×1013 cm-2 without carrier freeze-out, and constant mobilities around 900 cm2 V-1 s-1 below T=100 K. The 300-K channel conductivity of this junction is 3.2×10-3 Ω-1, which is higher than reported for other two-dimensional electron gases. By proper choice of the substrate orientation, domains of only the (111¯) ordering variant were present. TEM showed elongated shapes of average thickness 3.5-6 nm and length 75 nm in the (011) plane. By using Hall bars with different current directions, an asymmetry is observed for the contributions to the scattering mechanisms which determine the mobility: ``mesoscopic'' interface-roughness scattering for T<100 K and cluster scattering for 100300 K indicates strong electron-phonon coupling. This asymmetry shows that the domain length in the (011) plane is larger than that in the (011¯) plane. The magnetoresistance ρxx and the Hall resistance ρxy show oscillations in reciprocal magnetic field involving an excited subband i with ni2D=7.6×1011 cm-2, where 2D denotes two dimensional. The ρxy versus B curve shows features of a slight parallel conduction.

Akt substrate TBC1D1 regulates GLUT1 expression through the mTOR pathway in 3T3-L1 adipocytes

PubMed Central

Zhou, Qiong L.; Jiang, Zhen Y.; Holik, John; Chawla, Anil; Hagan, G. Nana; Leszyk, John; Czech, Michael P.

2010-01-01

Multiple studies have suggested that the protein kinase Akt/PKB (protein kinase B) is required for insulin-stimulated glucose transport in skeletal muscle and adipose cells. In an attempt to understand links between Akt activation and glucose transport regulation, we applied mass spectrometry-based proteomics and bioinformatics approaches to identify potential Akt substrates containing the phospho-Akt substrate motif RXRXXpS/T. The present study describes the identification of the Rab GAP (GTPase-activating protein)-domain containing protein TBC1D1 [TBC (Tre-2/Bub2/Cdc16) domain family, member 1], which is closely related to TBC1D4 [TBC domain family, member 4, also denoted AS160 (Akt substrate of 160 kDa)], as an Akt substrate that is phosphorylated at Thr590. RNAi (RNA interference)-me-diated silencing of TBC1D1 elevated basal deoxyglucose uptake by approx. 61% in 3T3-L1 mouse embryo adipocytes, while the suppression of TBC1D4 and RapGAP220 under the same conditions had little effect on basal and insulin-stimulated deoxy-glucose uptake. Silencing of TBC1D1 strongly increased expression of the GLUT1 glucose transporter but not GLUT4 in cultured adipocytes, whereas the decrease in TBC1D4 had no effect. Remarkably, loss of TBC1D1 in 3T3-L1 adipocytes activated the mTOR (mammalian target of rapamycin)-p70 S6 protein kinase pathway, and the increase in GLUT1 expression in the cells treated with TBC1D1 siRNA (small interfering RNA) was blocked by the mTOR inhibitor rapamycin. Furthermore, overexpression of the mutant TBC1D1-T590A, lacking the putative Akt/PKB phosphorylation site, inhibited insulin stimulation of p70 S6 kinase phosphorylation at Thr389, a phosphorylation induced by mTOR. Taken together, our data suggest that TBC1D1 may be involved in controlling GLUT1 glucose transporter expression through the mTOR-p70 S6 kinase pathway. PMID:18215134

[Glyburide prevents pulmonary artery smooth muscle cell proliferation and migration via inhibiting NLRP3 activation].

PubMed

Liu, Y F; Wang, W; Liu, T; Zhang, W; Liu, J; Wang, J

2017-06-12

Objective: To investigate whether glyburide prevents platelet-derived growth factor (PDGF) induced pulmonary artery smooth muscle cells(PASMCs) proliferation and migration via inhibiting nucleotide binding domain leucine-rich repeat-containing receptors protein 3(NLRP3) inflammasome activation. Methods: PASMCs were divided into 4 groups: control group, glyburide group, PDGF group and PDGF+ glyburide group. Cell proliferation and migration were assessed by MTT and Transwell respectively. The NLRP3 inflammasome activation was assessed by Western blot. Results: Compared with the control group, the protein expressions of NLRP3, caspase-1 and IL-1β in PASMCs were increased to (1.38±0.09, t =3.998, P <0.001), (1.32±0.1, t =3.268, P <0.01)and(1.43±0.19) ( t =2.096, P <0.05) folds in the PDGF group. Glyburide had no effect on NLRP3, caspase-1 and IL-1β expression as compared with the control group, while the NLRP3, caspase-1 and IL-1β were decreased by(20.49±7.6)% ( t =2.862, P <0.01), (32.94±3.44)% ( t =4.154, P <0.001) and (24.67±5.29)% ( t =2.335, P <0.05) in the PDGF+ glyburide group, respectively, as compared with the PDGF group. Compared with the control group, the PASMCs proliferation and migration in the PDGF group were significantly increased to (1.74±0.23, t =4.717, P <0.001) and (3.12±0.8, t =5.249, P <0.001) folds, respectively. Compared with the control group, glyburide had no effect on PASMCs proliferation and migration. In PDGF+ glyburide group, cell proliferation was reduced by (50.5±4.27)% ( t =4.462, P <0.001) and cell migration count was lower than in the PDGF group (42.77±2.84)% ( t =3.716, P <0.001). Conclusion: Glyburide could ameliorate PDGF-induced PASMCs proliferation and migration by inhibiting NLRP3 inflammasome activation.

Numeral series hidden in the distribution of atomic mass of amino acids to codon domains in the genetic code.

PubMed

Wohlin, Åsa

2015-03-21

The distribution of codons in the nearly universal genetic code is a long discussed issue. At the atomic level, the numeral series 2x(2) (x=5-0) lies behind electron shells and orbitals. Numeral series appear in formulas for spectral lines of hydrogen. The question here was if some similar scheme could be found in the genetic code. A table of 24 codons was constructed (synonyms counted as one) for 20 amino acids, four of which have two different codons. An atomic mass analysis was performed, built on common isotopes. It was found that a numeral series 5 to 0 with exponent 2/3 times 10(2) revealed detailed congruency with codon-grouped amino acid side-chains, simultaneously with the division on atom kinds, further with main 3rd base groups, backbone chains and with codon-grouped amino acids in relation to their origin from glycolysis or the citrate cycle. Hence, it is proposed that this series in a dynamic way may have guided the selection of amino acids into codon domains. Series with simpler exponents also showed noteworthy correlations with the atomic mass distribution on main codon domains; especially the 2x(2)-series times a factor 16 appeared as a conceivable underlying level, both for the atomic mass and charge distribution. Furthermore, it was found that atomic mass transformations between numeral systems, possibly interpretable as dimension degree steps, connected the atomic mass of codon bases with codon-grouped amino acids and with the exponent 2/3-series in several astonishing ways. Thus, it is suggested that they may be part of a deeper reference system. Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.

Controlling electric and magnetic currents in artificial spin ice (Presentation Recording)

NASA Astrophysics Data System (ADS)

Branford, Will R.

2015-09-01

I will discuss the collective properties of arrays of single domain nanomagnets called Artificial Spin Ice.1 The shape of each nanomagnet controls the magnetic anisotropy and the elements are closely spaced so dipolar interactions are important. The honeycomb lattice geometry prevents the satisfaction of all dipole interactions. Here I will show direct magnetic imaging studies of magnetic charge flow.2 The magnetic charge is carried by transverse domain walls and the chirality of the domain wall is found to control the direction of propagation.3,4 Injection of domain walls within the arrays with local fields is also explored.5 References 1 Branford, W. R., Ladak, S., Read, D. E., Zeissler, K. and Cohen, L. F. Emerging Chirality in Artificial Spin Ice. Science 335, 1597-1600, (2012). 2 Ladak, S., Read, D. E., Perkins, G. K., Cohen, L. F. and Branford, W. R. Direct observation of magnetic monopole defects in an artificial spin-ice system. Nature Physics 6, 359-363, (2010). 3 Burn, D. M., Chadha, M., Walton, S. K. and Branford, W. R. Dynamic interaction between domain walls and nanowire vertices. Phys. Rev. B 90, 144414, (2014). 4 Zeissler, K., Walton, S. K., Ladak, S., Read, D. E., Tyliszczak, T., Cohen, L. F. and Branford, W. R. The non-random walk of chiral magnetic charge carriers in artificial spin ice. Sci Rep-Uk 3, 1252, (2013). 5 Pushp, A., Phung, T., Rettner, C., Hughes, B. P., Yang, S. H., Thomas, L. and Parkin, S. S. P. Domain wall trajectory determined by its fractional topological edge defects. Nature Physics 9, 505-511, (2013).

The Design and Implementation of a Translator for Arithmetic and Boolean Expressions.

DTIC Science & Technology

1980-01-01

fault toleranc- P-or imTarop-r token.- or incorrect tok- n or(I-r. F C icD - MUS" hc-IV CnP 2J n,-)2ri 9 Iot t rq 3C003 G~T. 3OD 0L 3COC~ 5G F. 30005 ... 30005 .GE. ph 50015 60. C 30006 .LE. DP 50016 61. C RELPNT-INTEGER, POINTER TO ENTRIES IN RELOPS ARRAYY 62. C TEMP -INTEGER, USED FOR DETERMINING IF...30002, 50012, 30003, 50013, 30004, 50014, 30005 , 50015, 71. 1 30006, 50016/, SUB/50006/, THEN/142408/ 72. C 73. C ******** EXECUTABLE CODE******** 74

Finite Element Flow Code Optimization on the Cray T3D,

DTIC Science & Technology

1997-04-01

present time, the system is configured with 512 processing elements and 32.8 Cigabytes of memory. Through a gift of time from MSCI and other arrangements, the AHPCRC has limited access to this system.

Superharmonic imaging with chirp coded excitation: filtering spectrally overlapped harmonics.

PubMed

Harput, Sevan; McLaughlan, James; Cowell, David M J; Freear, Steven

2014-11-01

Superharmonic imaging improves the spatial resolution by using the higher order harmonics generated in tissue. The superharmonic component is formed by combining the third, fourth, and fifth harmonics, which have low energy content and therefore poor SNR. This study uses coded excitation to increase the excitation energy. The SNR improvement is achieved on the receiver side by performing pulse compression with harmonic matched filters. The use of coded signals also introduces new filtering capabilities that are not possible with pulsed excitation. This is especially important when using wideband signals. For narrowband signals, the spectral boundaries of the harmonics are clearly separated and thus easy to filter; however, the available imaging bandwidth is underused. Wideband excitation is preferable for harmonic imaging applications to preserve axial resolution, but it generates spectrally overlapping harmonics that are not possible to filter in time and frequency domains. After pulse compression, this overlap increases the range side lobes, which appear as imaging artifacts and reduce the Bmode image quality. In this study, the isolation of higher order harmonics was achieved in another domain by using the fan chirp transform (FChT). To show the effect of excitation bandwidth in superharmonic imaging, measurements were performed by using linear frequency modulated chirp excitation with varying bandwidths of 10% to 50%. Superharmonic imaging was performed on a wire phantom using a wideband chirp excitation. Results were presented with and without applying the FChT filtering technique by comparing the spatial resolution and side lobe levels. Wideband excitation signals achieved a better resolution as expected, however range side lobes as high as -23 dB were observed for the superharmonic component of chirp excitation with 50% fractional bandwidth. The proposed filtering technique achieved >50 dB range side lobe suppression and improved the image quality without affecting the axial resolution.

A Novel Multi-Scale Domain Overlapping CFD/STH Coupling Methodology for Multi-Dimensional Flows Relevant to Nuclear Applications

NASA Astrophysics Data System (ADS)

Grunloh, Timothy P.

The objective of this dissertation is to develop a 3-D domain-overlapping coupling method that leverages the superior flow field resolution of the Computational Fluid Dynamics (CFD) code STAR-CCM+ and the fast execution of the System Thermal Hydraulic (STH) code TRACE to efficiently and accurately model thermal hydraulic transport properties in nuclear power plants under complex conditions of regulatory and economic importance. The primary contribution is the novel Stabilized Inertial Domain Overlapping (SIDO) coupling method, which allows for on-the-fly correction of TRACE solutions for local pressures and velocity profiles inside multi-dimensional regions based on the results of the CFD simulation. The method is found to outperform the more frequently-used domain decomposition coupling methods. An STH code such as TRACE is designed to simulate large, diverse component networks, requiring simplifications to the fluid flow equations for reasonable execution times. Empirical correlations are therefore required for many sub-grid processes. The coarse grids used by TRACE diminish sensitivity to small scale geometric details such as Reactor Pressure Vessel (RPV) internals. A CFD code such as STAR-CCM+ uses much finer computational meshes that are sensitive to the geometric details of reactor internals. In turbulent flows, it is infeasible to fully resolve the flow solution, but the correlations used to model turbulence are at a low level. The CFD code can therefore resolve smaller scale flow processes. The development of a 3-D coupling method was carried out with the intention of improving predictive capabilities of transport properties in the downcomer and lower plenum regions of an RPV in reactor safety calculations. These regions are responsible for the multi-dimensional mixing effects that determine the distribution at the core inlet of quantities with reactivity implications, such as fluid temperature and dissolved neutron absorber concentration.

Runaway electron production in DIII-D killer pellet experiments, calculated with the CQL3D/KPRAD model

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

Harvey, R. W.; Chan, V. S.; Chiu, S. C.

2000-11-01

Runaway electrons are calculated to be produced during the rapid plasma cooling resulting from ''killer pellet'' injection experiments, in general agreement with observations in the DIII-D [J. L. Luxon , Plasma Physics and Controlled Nuclear Fusion Research 1986 (International Atomic Energy Agency, Vienna, 1987), Vol. I, p. 159] tokamak. The time-dependent dynamics of the kinetic runaway distributions are obtained with the CQL3D [R. W. Harvey and M. G. McCoy, ''The CQL3D Code,'' in Proceedings of the IAEA Technical Committee Meeting on Numerical Modeling, Montreal, 1992 (International Atomic Energy Agency, Vienna, 1992), p. 489] collisional Fokker--Planck code, including the effect ofmore » small and large angle collisions and stochastic magnetic field transport losses. The background density, temperature, and Z{sub eff} are evolved according to the KPRAD [D. G. Whyte and T. E. Evans , in Proceedings of the 24th European Conference on Controlled Fusion and Plasma Physics, Berchtesgaden, Germany (European Physical Society, Petit-Lancy, 1997), Vol. 21A, p. 1137] deposition and radiation model of pellet--plasma interactions. Three distinct runway mechanisms are apparent: (1) prompt ''hot-tail runaways'' due to the residual hot electron tail remaining from the pre-cooling phase, (2) ''knock-on'' runaways produced by large-angle Coulomb collisions on existing high energy electrons, and (3) Dreicer ''drizzle'' runaway electrons due to diffusion of electrons up to the critical velocity for electron runaway. For electron densities below {approx}1x10{sup 15}cm{sup -3}, the hot-tail runaways dominate the early time evolution, and provide the seed population for late time knock-on runaway avalanche. For small enough stochastic magnetic field transport losses, the knock-on production of electrons balances the losses at late times. For losses due to radial magnetic field perturbations in excess of {approx}0.1% of the background field, i.e., {delta}B{sub r}/B{>=}0.001, the losses prevent late-time electron runaway.« less

Identification and characterization of two novel toxins expressed by the lethal honey bee pathogen Paenibacillus larvae, the causative agent of American foulbrood.

PubMed

Fünfhaus, Anne; Poppinga, Lena; Genersch, Elke

2013-11-01

Paenibacillus larvae is a Gram-positive bacterial pathogen causing the epizootic American foulbrood in honey bee larvae. Four so-called enterobacterial repetitive intergenic consensus (ERIC) genotypes of P. larvae exist with P. larvae genotypes ERIC I and ERIC II being responsible for disease outbreaks all over the world. Very few molecular data on the pathogen, on pathogenesis or on virulence factors exist. We now identified two genomic loci in P. larvae ERIC I coding for two binary AB toxins, Plx1 and Plx2. In silico analyses revealed that Plx1 is the third member of an enigmatic family of AB toxins so far only comprising MTX1 of Lysinibacillus sphaericus and pierisin-like toxins expressed by several butterflies. Plx2 is also remarkable because the A-domain is highly similar to C3 exoenzymes, which normally are single domain proteins, while the B-domain is homologous to B-domains of C2-toxins. We constructed P. larvae mutants lacking expression of Plx1, Plx2 or both toxins and demonstrated that these toxins are important virulence factors for P. larvae ERIC I. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

Effects of Resistance Training on Fatigue-Related Domains of Quality of Life and Mood During Pregnancy: A Randomized Trial in Pregnant Women With Increased Risk of Back Pain.

PubMed

OʼConnor, Patrick J; Poudevigne, Mélanie S; Johnson, Kristen E; Brito de Araujo, Juliana; Ward-Ritacco, Christie L

2018-04-01

The aim of the study was to test whether the adoption of twice weekly, low-to-moderate intensity resistance training during weeks 22 to 34 of pregnancy can improve quality of life and mood. A parallel-group trial was conducted. Women in their second trimester (N = 134) were randomly assigned to 12 weeks of wait list, bimonthly pregnancy education classes, or twice weekly low-to-moderate intensity resistance training. Resistance training involved one abdominal exercise with no external load and five exercises (leg extension, leg press, arm lat pull, leg curl, and lumbar extension) with an external load that gradually progressed, and the total active exercise time during each exercise session was approximately 17 minutes. Quality of life and mood were measured before and after the interventions using the 36-item Short Form Health Survey and Profile of Mood States. Intent-to-treat mixed-model analyses of variance (3 groups by 2 times, pre- and postintervention) tested the hypothesis that outcomes would worsen for the controls and not change or improve for the resistance training group. The group by time interaction (F(2,131) = 3.144, η = .046, p = .046) for 36-item Short Form Health Survey vitality and subsequent simple main effects showed that scores were unchanged across time after resistance training (-1.8 (14.8)) but significantly decreased for the education (-6.44 (12.69), t = 3.408, df = 44, p = .001) and wait list (-9.11 (14.78), t = 4.135, df = 44, p < .001) groups, whereas posttest vitality scores for the pregnancy group (45.9 (16.9)) were significantly higher than the wait list (40.1 (16.3), t = 1.989, df = 87, p = .05) but not the education group (42.1 (15.4), p = .27). Profile of mood states fatigue scores showed a similar pattern. Adverse changes in symptoms of energy and fatigue during pregnancy are attenuated by adopting low-to-moderate intensity resistance training. Clinicaltrials.gov, NCT02557893.

Generalized three-dimensional experimental lightning code (G3DXL) user's manual

NASA Technical Reports Server (NTRS)

Kunz, Karl S.

1986-01-01

Information concerning the programming, maintenance and operation of the G3DXL computer program is presented and the theoretical basis for the code is described. The program computes time domain scattering fields and surface currents and charges induced by a driving function on and within a complex scattering object which may be perfectly conducting or a lossy dielectric. This is accomplished by modeling the object with cells within a three-dimensional, rectangular problem space, enforcing the appropriate boundary conditions and differencing Maxwell's equations in time. In the present version of the program, the driving function can be either the field radiated by a lightning strike or a direct lightning strike. The F-106 B aircraft is used as an example scattering object.

Improving coding accuracy in an academic practice.

PubMed

Nguyen, Dana; O'Mara, Heather; Powell, Robert

2017-01-01

Practice management has become an increasingly important component of graduate medical education. This applies to every practice environment; private, academic, and military. One of the most critical aspects of practice management is documentation and coding for physician services, as they directly affect the financial success of any practice. Our quality improvement project aimed to implement a new and innovative method for teaching billing and coding in a longitudinal fashion in a family medicine residency. We hypothesized that implementation of a new teaching strategy would increase coding accuracy rates among residents and faculty. Design: single group, pretest-posttest. military family medicine residency clinic. Study populations: 7 faculty physicians and 18 resident physicians participated as learners in the project. Educational intervention: monthly structured coding learning sessions in the academic curriculum that involved learner-presented cases, small group case review, and large group discussion. overall coding accuracy (compliance) percentage and coding accuracy per year group for the subjects that were able to participate longitudinally. Statistical tests used: average coding accuracy for population; paired t test to assess improvement between 2 intervention periods, both aggregate and by year group. Overall coding accuracy rates remained stable over the course of time regardless of the modality of the educational intervention. A paired t test was conducted to compare coding accuracy rates at baseline (mean (M)=26.4%, SD=10%) to accuracy rates after all educational interventions were complete (M=26.8%, SD=12%); t24=-0.127, P=.90. Didactic teaching and small group discussion sessions did not improve overall coding accuracy in a residency practice. Future interventions could focus on educating providers at the individual level.

Comparison of a 3-D GPU-Assisted Maxwell Code and Ray Tracing for Reflectometry on ITER

NASA Astrophysics Data System (ADS)

Gady, Sarah; Kubota, Shigeyuki; Johnson, Irena

2015-11-01

Electromagnetic wave propagation and scattering in magnetized plasmas are important diagnostics for high temperature plasmas. 1-D and 2-D full-wave codes are standard tools for measurements of the electron density profile and fluctuations; however, ray tracing results have shown that beam propagation in tokamak plasmas is inherently a 3-D problem. The GPU-Assisted Maxwell Code utilizes the FDTD (Finite-Difference Time-Domain) method for solving the Maxwell equations with the cold plasma approximation in a 3-D geometry. Parallel processing with GPGPU (General-Purpose computing on Graphics Processing Units) is used to accelerate the computation. Previously, we reported on initial comparisons of the code results to 1-D numerical and analytical solutions, where the size of the computational grid was limited by the on-board memory of the GPU. In the current study, this limitation is overcome by using domain decomposition and an additional GPU. As a practical application, this code is used to study the current design of the ITER Low Field Side Reflectometer (LSFR) for the Equatorial Port Plug 11 (EPP11). A detailed examination of Gaussian beam propagation in the ITER edge plasma will be presented, as well as comparisons with ray tracing. This work was made possible by funding from the Department of Energy for the Summer Undergraduate Laboratory Internship (SULI) program. This work is supported by the US DOE Contract No.DE-AC02-09CH11466 and DE-FG02-99-ER54527.

The ubiquitin-homology protein, DAP-1, associates with tumor necrosis factor receptor (p60) death domain and induces apoptosis.

PubMed

Liou, M L; Liou, H C

1999-04-09

The tumor necrosis factor receptor, p60 (TNF-R1), transduces death signals via the association of its cytoplasmic domain with several intracellular proteins. By screening a mammalian cDNA library using the yeast two-hybrid cloning technique, we isolated a ubiquitin-homology protein, DAP-1, which specifically interacts with the cytoplasmic death domain of TNF-R1. Sequence analysis reveals that DAP-1 shares striking sequence homology with the yeast SMT3 protein that is essential for the maintenance of chromosome integrity during mitosis (Meluh, P. B., and Koshland, D. (1995) Mol. Biol. Cell 6, 793-807). DAP-1 is nearly identical to PIC1, a protein that interacts with the PML tumor suppressor implicated in acute promyelocytic leukemia (Boddy, M. N., Howe, K., Etkin, L. D., Solomon, E., and Freemont, P. S. (1996) Oncogene 13, 971-982), and the sentrin protein, which associates with the Fas death receptor (Okura, T., Gong, L., Kamitani, T., Wada, T., Okura, I., Wei, C. F., Chang, H. M., and Yeh, E. T. (1996) J. Immunol. 157, 4277-4281). The in vivo interaction between DAP-1 and TNF-R1 was further confirmed in mammalian cells. In transient transfection assays, overexpression of DAP-1 suppresses NF-kappaB/Rel activity in 293T cells, a human kidney embryonic carcinoma cell line. Overexpression of either DAP-1 or sentrin causes apoptosis of TNF-sensitive L929 fibroblast cell line, as well as TNF-resistant osteosarcoma cell line, U2OS. Furthermore, the dominant negative Fas-associated death domain protein (FADD) protein blocks the cell death induced by either DAP-1 or FADD. Collectively, these observations highly suggest a role for DAP-1 in mediating TNF-induced cell death signaling pathways, presumably through the recruitment of FADD death effector.

Identification of Scattering Mechanisms from Measured Impulse Response Signatures of Several Conducting Objects.

DTIC Science & Technology

1984-02-01

conducting sphere 35 compared to inverse transform of exact solution. 4-5. Measured impulse response of a conducting 2:1 right 37 circular cylinder with...frequency domain. This is equivalent to multiplication in the time domain by the inverse transform of w(n), which is shown in Figure 3-1 for N=15. The...equivalent pulse width from 0.066 T for the rectangular window to 0.10 T for the Hanning window. The inverse transform of the Hanning window is shown

Hepatic F-Box Protein FBXW7 Maintains Glucose Homeostasis Through Degradation of Fetuin-A.

PubMed

Zhao, Jiejie; Xiong, Xuelian; Li, Yao; Liu, Xing; Wang, Tao; Zhang, Hong; Jiao, Yang; Jiang, Jingjing; Zhang, Huijie; Tang, Qiqun; Gao, Xin; Li, Xuejun; Lu, Yan; Liu, Bin; Hu, Cheng; Li, Xiaoying

2018-05-01

Type 2 diabetes mellitus (T2DM) has become one of the most serious and long-term threats to human health. However, the molecular mechanism that links obesity to insulin resistance remains largely unknown. Here, we show that F-box and WD repeat domain-containing 7 (FBXW7), an E3 ubiquitin protein ligase, is markedly downregulated in the liver of two obese mouse models and obese human subjects. We further identify a functional low-frequency human FBXW7 coding variant (p.Ala204Thr) in the Chinese population, which is associated with elevated blood glucose and T2DM risk. Notably, mice with liver-specific knockout of FBXW7 develop hyperglycemia, glucose intolerance, and insulin resistance even on a normal chow diet. Conversely, overexpression of FBXW7 in the liver not only prevents the development of high-fat diet-induced insulin resistance but also attenuates the disease signature of obese mice. Mechanistically, FBXW7 directly binds to hepatokine fetuin-A to induce its ubiquitination and subsequent proteasomal degradation, comprising an important mechanism maintaining glucose homeostasis. Thus, we provide evidence showing a beneficial role of FBXW7 in glucose homeostasis. © 2018 by the American Diabetes Association.

Shared acoustic codes underlie emotional communication in music and speech—Evidence from deep transfer learning

PubMed Central

Schuller, Björn

2017-01-01

Music and speech exhibit striking similarities in the communication of emotions in the acoustic domain, in such a way that the communication of specific emotions is achieved, at least to a certain extent, by means of shared acoustic patterns. From an Affective Sciences points of view, determining the degree of overlap between both domains is fundamental to understand the shared mechanisms underlying such phenomenon. From a Machine learning perspective, the overlap between acoustic codes for emotional expression in music and speech opens new possibilities to enlarge the amount of data available to develop music and speech emotion recognition systems. In this article, we investigate time-continuous predictions of emotion (Arousal and Valence) in music and speech, and the Transfer Learning between these domains. We establish a comparative framework including intra- (i.e., models trained and tested on the same modality, either music or speech) and cross-domain experiments (i.e., models trained in one modality and tested on the other). In the cross-domain context, we evaluated two strategies—the direct transfer between domains, and the contribution of Transfer Learning techniques (feature-representation-transfer based on Denoising Auto Encoders) for reducing the gap in the feature space distributions. Our results demonstrate an excellent cross-domain generalisation performance with and without feature representation transfer in both directions. In the case of music, cross-domain approaches outperformed intra-domain models for Valence estimation, whereas for Speech intra-domain models achieve the best performance. This is the first demonstration of shared acoustic codes for emotional expression in music and speech in the time-continuous domain. PMID:28658285

Shared acoustic codes underlie emotional communication in music and speech-Evidence from deep transfer learning.

PubMed

Coutinho, Eduardo; Schuller, Björn

2017-01-01

Music and speech exhibit striking similarities in the communication of emotions in the acoustic domain, in such a way that the communication of specific emotions is achieved, at least to a certain extent, by means of shared acoustic patterns. From an Affective Sciences points of view, determining the degree of overlap between both domains is fundamental to understand the shared mechanisms underlying such phenomenon. From a Machine learning perspective, the overlap between acoustic codes for emotional expression in music and speech opens new possibilities to enlarge the amount of data available to develop music and speech emotion recognition systems. In this article, we investigate time-continuous predictions of emotion (Arousal and Valence) in music and speech, and the Transfer Learning between these domains. We establish a comparative framework including intra- (i.e., models trained and tested on the same modality, either music or speech) and cross-domain experiments (i.e., models trained in one modality and tested on the other). In the cross-domain context, we evaluated two strategies-the direct transfer between domains, and the contribution of Transfer Learning techniques (feature-representation-transfer based on Denoising Auto Encoders) for reducing the gap in the feature space distributions. Our results demonstrate an excellent cross-domain generalisation performance with and without feature representation transfer in both directions. In the case of music, cross-domain approaches outperformed intra-domain models for Valence estimation, whereas for Speech intra-domain models achieve the best performance. This is the first demonstration of shared acoustic codes for emotional expression in music and speech in the time-continuous domain.

Mapping of the minimal inorganic phosphate transporting unit of human PiT2 suggests a structure universal to PiT-related proteins from all kingdoms of life.

PubMed

Bøttger, Pernille; Pedersen, Lene

2011-05-17

The inorganic (Pi) phosphate transporter (PiT) family comprises known and putative Na(+)- or H(+)-dependent Pi-transporting proteins with representatives from all kingdoms. The mammalian members are placed in the outer cell membranes and suggested to supply cells with Pi to maintain house-keeping functions. Alignment of protein sequences representing PiT family members from all kingdoms reveals the presence of conserved amino acids and that bacterial phosphate permeases and putative phosphate permeases from archaea lack substantial parts of the protein sequence when compared to the mammalian PiT family members. Besides being Na(+)-dependent P(i) (NaP(i)) transporters, the mammalian PiT paralogs, PiT1 and PiT2, also are receptors for gamma-retroviruses. We have here exploited the dual-function of PiT1 and PiT2 to study the structure-function relationship of PiT proteins. We show that the human PiT2 histidine, H(502), and the human PiT1 glutamate, E(70),--both conserved in eukaryotic PiT family members--are critical for P(i) transport function. Noticeably, human PiT2 H(502) is located in the C-terminal PiT family signature sequence, and human PiT1 E(70) is located in ProDom domains characteristic for all PiT family members.A human PiT2 truncation mutant, which consists of the predicted 10 transmembrane (TM) domain backbone without a large intracellular domain (human PiT2ΔR(254)-V(483)), was found to be a fully functional P(i) transporter. Further truncation of the human PiT2 protein by additional removal of two predicted TM domains together with the large intracellular domain created a mutant that resembles a bacterial phosphate permease and an archaeal putative phosphate permease. This human PiT2 truncation mutant (human PiT2ΔL(183)-V(483)) did also support P(i) transport albeit at very low levels. The results suggest that the overall structure of the P(i)-transporting unit of the PiT family proteins has remained unchanged during evolution. Moreover, in combination, our studies of the gene structure of the human PiT1 and PiT2 genes (SLC20A1 and SLC20A2, respectively) and alignment of protein sequences of PiT family members from all kingdoms, along with the studies of the dual functions of the human PiT paralogs show that these proteins are excellent as models for studying the evolution of a protein's structure-function relationship. © 2011 Bøttger and Pedersen; licensee BioMed Central Ltd.

Parallel Semi-Implicit Spectral Element Atmospheric Model

NASA Astrophysics Data System (ADS)

Fournier, A.; Thomas, S.; Loft, R.

2001-05-01

The shallow-water equations (SWE) have long been used to test atmospheric-modeling numerical methods. The SWE contain essential wave-propagation and nonlinear effects of more complete models. We present a semi-implicit (SI) improvement of the Spectral Element Atmospheric Model to solve the SWE (SEAM, Taylor et al. 1997, Fournier et al. 2000, Thomas & Loft 2000). SE methods are h-p finite element methods combining the geometric flexibility of size-h finite elements with the accuracy of degree-p spectral methods. Our work suggests that exceptional parallel-computation performance is achievable by a General-Circulation-Model (GCM) dynamical core, even at modest climate-simulation resolutions (>1o). The code derivation involves weak variational formulation of the SWE, Gauss(-Lobatto) quadrature over the collocation points, and Legendre cardinal interpolators. Appropriate weak variation yields a symmetric positive-definite Helmholtz operator. To meet the Ladyzhenskaya-Babuska-Brezzi inf-sup condition and avoid spurious modes, we use a staggered grid. The SI scheme combines leapfrog and Crank-Nicholson schemes for the nonlinear and linear terms respectively. The localization of operations to elements ideally fits the method to cache-based microprocessor computer architectures --derivatives are computed as collections of small (8x8), naturally cache-blocked matrix-vector products. SEAM also has desirable boundary-exchange communication, like finite-difference models. Timings on on the IBM SP and Compaq ES40 supercomputers indicate that the SI code (20-min timestep) requires 1/3 the CPU time of the explicit code (2-min timestep) for T42 resolutions. Both codes scale nearly linearly out to 400 processors. We achieved single-processor performance up to 30% of peak for both codes on the 375-MHz IBM Power-3 processors. Fast computation and linear scaling lead to a useful climate-simulation dycore only if enough model time is computed per unit wall-clock time. An efficient SI solver is essential to substantially increase this rate. Parallel preconditioning for an iterative conjugate-gradient elliptic solver is described. We are building a GCM dycore capable of 200 GF% lOPS sustained performance on clustered RISC/cache architectures using hybrid MPI/OpenMP programming.

Suicidal Ideation and Schizophrenia: Contribution of Appraisal, Stigmatization, and Cognition.

PubMed

Stip, Emmanuel; Caron, Jean; Tousignant, Michel; Lecomte, Yves

2017-10-01

To predict suicidal ideation in people with schizophrenia, certain studies have measured its relationship with the variables of defeat and entrapment. The relationships are positive, but their interactions remain undefined. To further their understanding, this research sought to measure the relationship between suicidal ideation with the variables of loss, entrapment, and humiliation. The convenience sample included 30 patients with schizophrenia spectrum disorders. The study was prospective (3 measurement times) during a 6-month period. Results were analyzed by stepwise multiple regression. The contribution of the 3 variables to the variance of suicidal ideation was not significant at any of the 3 times (T1: 16.2%, P = 0.056; T2: 19.9%, P = 0.117; T3: 11.2%, P = 0.109). Further analyses measured the relationship between the variables of stigmatization, perceived cognitive dysfunction, symptoms, depression, self-esteem, reason to live, spirituality, social provision, and suicidal ideation. Stepwise multiple regression demonstrated that the contribution of the variables of stigmatization and perceived cognitive dysfunction to the variance of suicidal ideation was significant at all 3 times (T1: 41.7.5%, P = 0.000; T2: 35.2%, P = 0.001; T3: 21.5%, P = 0.012). Yet, over time, the individual contribution of the variables changed: T1, stigmatization (β = 0.518; P = 0.002); T2, stigmatization (β = 0.394; P = 0.025) and perceived cognitive dysfunction (β = 0.349; P = 0.046). Then, at T3, only perceived cognitive dysfunction contributed significantly to suicidal ideation (β = 0.438; P = 0.016). The results highlight the importance of the contribution of the variables of perceived cognitive dysfunction and stigmatization in the onset of suicidal ideation in people with schizophrenia spectrum disorders.

Suicidal Ideation and Schizophrenia: Contribution of Appraisal, Stigmatization, and Cognition

PubMed Central

Stip, Emmanuel; Caron, Jean; Tousignant, Michel

2017-01-01

Objective: To predict suicidal ideation in people with schizophrenia, certain studies have measured its relationship with the variables of defeat and entrapment. The relationships are positive, but their interactions remain undefined. To further their understanding, this research sought to measure the relationship between suicidal ideation with the variables of loss, entrapment, and humiliation. Method: The convenience sample included 30 patients with schizophrenia spectrum disorders. The study was prospective (3 measurement times) during a 6-month period. Results were analyzed by stepwise multiple regression. Results: The contribution of the 3 variables to the variance of suicidal ideation was not significant at any of the 3 times (T1: 16.2%, P = 0.056; T2: 19.9%, P = 0.117; T3: 11.2%, P = 0.109). Further analyses measured the relationship between the variables of stigmatization, perceived cognitive dysfunction, symptoms, depression, self-esteem, reason to live, spirituality, social provision, and suicidal ideation. Stepwise multiple regression demonstrated that the contribution of the variables of stigmatization and perceived cognitive dysfunction to the variance of suicidal ideation was significant at all 3 times (T1: 41.7.5%, P = 0.000; T2: 35.2%, P = 0.001; T3: 21.5%, P = 0.012). Yet, over time, the individual contribution of the variables changed: T1, stigmatization (β = 0.518; P = 0.002); T2, stigmatization (β = 0.394; P = 0.025) and perceived cognitive dysfunction (β = 0.349; P = 0.046). Then, at T3, only perceived cognitive dysfunction contributed significantly to suicidal ideation (β = 0.438; P = 0.016). Conclusion: The results highlight the importance of the contribution of the variables of perceived cognitive dysfunction and stigmatization in the onset of suicidal ideation in people with schizophrenia spectrum disorders. PMID:28673099

An Infrastructure for UML-Based Code Generation Tools

NASA Astrophysics Data System (ADS)

Wehrmeister, Marco A.; Freitas, Edison P.; Pereira, Carlos E.

The use of Model-Driven Engineering (MDE) techniques in the domain of distributed embedded real-time systems are gain importance in order to cope with the increasing design complexity of such systems. This paper discusses an infrastructure created to build GenERTiCA, a flexible tool that supports a MDE approach, which uses aspect-oriented concepts to handle non-functional requirements from embedded and real-time systems domain. GenERTiCA generates source code from UML models, and also performs weaving of aspects, which have been specified within the UML model. Additionally, this paper discusses the Distributed Embedded Real-Time Compact Specification (DERCS), a PIM created to support UML-based code generation tools. Some heuristics to transform UML models into DERCS, which have been implemented in GenERTiCA, are also discussed.

A comparison of VLSI architectures for time and transform domain decoding of Reed-Solomon codes

NASA Technical Reports Server (NTRS)

Hsu, I. S.; Truong, T. K.; Deutsch, L. J.; Satorius, E. H.; Reed, I. S.

1988-01-01

It is well known that the Euclidean algorithm or its equivalent, continued fractions, can be used to find the error locator polynomial needed to decode a Reed-Solomon (RS) code. It is shown that this algorithm can be used for both time and transform domain decoding by replacing its initial conditions with the Forney syndromes and the erasure locator polynomial. By this means both the errata locator polynomial and the errate evaluator polynomial can be obtained with the Euclidean algorithm. With these ideas, both time and transform domain Reed-Solomon decoders for correcting errors and erasures are simplified and compared. As a consequence, the architectures of Reed-Solomon decoders for correcting both errors and erasures can be made more modular, regular, simple, and naturally suitable for VLSI implementation.

Job Demands, Burnout, and Teamwork in Healthcare Professionals Working in a General Hospital that Was Analysed At Two Points in Time.

PubMed

Mijakoski, Dragan; Karadzhinska-Bislimovska, Jovanka; Stoleski, Sasho; Minov, Jordan; Atanasovska, Aneta; Bihorac, Elida

2018-04-15

The purpose of the paper was to assess job demands, burnout, and teamwork in healthcare professionals (HPs) working in a general hospital that was analysed at two points in time with a time lag of three years. Time 1 respondents (N = 325) were HPs who participated during the first wave of data collection (2011). Time 2 respondents (N = 197) were HPs from the same hospital who responded at Time 2 (2014). Job demands, burnout, and teamwork were measured with Hospital Experience Scale, Maslach Burnout Inventory, and Hospital Survey on Patient Safety Culture, respectively. Significantly higher scores of emotional exhaustion (21.03 vs. 15.37, t = 5.1, p < 0.001), depersonalization (4.48 vs. 2.75, t = 3.8, p < 0.001), as well as organizational (2.51 vs. 2.34, t = 2.38, p = 0.017), emotional (2.46 vs. 2.25, t = 3.68, p < 0.001), and cognitive (2.82 vs. 2.64, t = 2.68, p = 0.008) job demands were found at Time 2. Teamwork levels were similar at both points in time (Time 1 = 3.84 vs. Time 2 = 3.84, t = 0.043, p = 0.97). Actual longitudinal study revealed significantly higher mean values of emotional exhaustion and depersonalization in 2014 that could be explained by significantly increased job demands between analysed points in time.

P- T- t constraints on the development of the Doi Inthanon metamorphic core complex domain and implications for the evolution of the western gneiss belt, northern Thailand

NASA Astrophysics Data System (ADS)

Macdonald, A. S.; Barr, S. M.; Miller, B. V.; Reynolds, P. H.; Rhodes, B. P.; Yokart, B.

2010-01-01

The western gneiss belt in northern Thailand is exposed within two overlapping Cenozoic structural domains: the extensional Doi Inthanon metamorphic core complex domain located west of the Chiang Mai basin, and the Mae Ping strike-slip fault domain located west of the Tak batholith. New P- T estimates and U-Pb and 40Ar/ 39Ar age determinations from the Doi Inthanon domain show that the gneiss there records a complex multi-stage history that can be represented by a clockwise P- T- t path. U-Pb zircon and titanite dating of mylonitic calc-silicate gneiss from the Mae Wang area of the complex indicates that the paragneissic sequence experienced high-grade, medium-pressure metamorphism (M1) in the Late Triassic - Early Jurassic (ca. 210 Ma), in good agreement with previously determined zircon ages from the underlying core orthogneiss exposed on Doi Inthanon. Late Cretaceous monazite ages of 84 and 72 Ma reported previously from the core orthogneiss are attributed to a thermal overprint (M2) to upper-amphibolite facies in the sillimanite field. U-Pb zircon and monazite dating of granitic mylonite from the Doi Suthep area of the complex provides an upper age limit of 40 Ma (Late Eocene) for the early stage(s) of development of the actual core complex, by initially ductile, low-angle extensional shearing under lower amphibolite-facies conditions (M3), accompanied by near-isothermal diapiric rise and decompression melting. 40Ar/ 39Ar laserprobe dating of muscovite from both Doi Suthep and Doi Inthanon provided Miocene ages of ca. 26-15 Ma, representing cooling through the ca. 350 °C isotherm and marking late-stage development of the core complex by detachment faulting of the cover rocks and isostatic uplift of the sheared core zone and mantling gneisses in the footwall. Similarities in the thermochronology of high-grade gneisses exposed in the core complex and shear zone domains in the western gneiss belt of northern Thailand (and also in northern Vietnam, Laos, Yunnan, and central Myanmar) suggest a complex regional response to indentation of Southeast Asia by India.

Molecular LEGO by domain-imprinting of cytochrome P450 BM3.

PubMed

Jetzschmann, K J; Yarman, A; Rustam, L; Kielb, P; Urlacher, V B; Fischer, A; Weidinger, I M; Wollenberger, U; Scheller, F W

2018-04-01

Electrosynthesis of the MIP nano-film after binding of the separated domains or holo-cytochrome BM3 via an engineered anchor should result in domain-specific cavities in the polymer layer. Both the two domains and the holo P450 BM3 have been bound prior polymer deposition via a N-terminal engineered his6-anchor to the electrode surface. Each step of MIP preparation was characterized by cyclic voltammetry of the redox-marker ferricyanide. Rebinding after template removal was evaluated by quantifying the suppression of the diffusive permeability of the signal for ferricyanide and by the NADH-dependent reduction of cytochrome c by the reductase domain (BMR). The working hypothesis is verified by the discrimination of the two domains by the respective MIPs: The holoenzyme P450 BM3 was ca. 5.5 times more effectively recognized by the film imprinted with the oxidase domain (BMO) as compared to the BMR-MIP or the non-imprinted polymer (NIP). Obviously, a cavity is formed during the imprinting process around the his 6 -tag-anchored BMR which cannot accommodate the broader BMO or the P450 BM3. The affinity of the MIP towards P450 BM3 is comparable with that to the monomer in solution. The his 6 -tagged P450 BM3 binds (30 percent) stronger which shows the additive effect of the interaction with the MIP and the binding to the electrode. Copyright © 2018. Published by Elsevier B.V.

Structural analysis of bacteriophage-encoded peptidoglycan hydrolase domain KMV36C: crystallization and preliminary X-ray diffraction

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

Van Hecke, Kristof, E-mail: kristof.vanhecke@chem.kuleuven.be; Briers, Yves; Derua, Rita

2008-04-01

Crystallization and X-ray data collection of the C-terminus of gp36 from bacteriophage ϕKMV (KMV36C) are reported. The C-terminus of gp36 of bacteriophage ϕKMV (KMV36C) functions as a particle-associated muramidase, presumably as part of the injection needle of the ϕKMV genome during infection. Crystals of KMV36C were obtained by hanging-drop vapour diffusion and diffracted to a resolution of 1.6 Å. The crystals belong to the cubic space group P432, with unit-cell parameters a = b = c = 102.52 Å. KMV36C shows 30% sequence identity to T4 lysozyme (PDB code)

Low Density Real Gas Flows About Hypersonic Vehicles.

DTIC Science & Technology

1991-11-01

equations with fully-coupled finite rate air chemistry. The development of the HYLDA code was motivated by the difficulty of current wind tunnel...2ps,,.,, - psj = , (3-30) PN. 2pNwa - pNead u Uadj v Vadj w T Wadj bc 2TLMau - TadJ where PS4 -- PSj if noncatalytic wall = calculated if catalytic wall

Health-Related Quality of Life in Relation to Obesity Grade, Type 2 Diabetes, Metabolic Syndrome and Inflammation

PubMed Central

Slagter, Sandra N.; van Vliet-Ostaptchouk, Jana V.; van Beek, André P.; Keers, Joost C.; Lutgers, Helen L.; van der Klauw, Melanie M.; Wolffenbuttel, Bruce H. R.

2015-01-01

Background Health-related quality of life (HR-QoL) may be compromised in obese individuals, depending on the presence of other complications. The aim of this study is to assess the effect of obesity-related conditions on HR-QoL. These conditions are i) grade of obesity with and without type 2 diabetes (T2D), ii) metabolic syndrome (MetS), and iii) level of inflammation. Methods From the Dutch LifeLines Cohort Study we included 13,686 obese individuals, aged 18–80 years. HR-QoL was measured with the RAND 36-Item Health Survey which encompasses eight health domains. We calculated the percentage of obese individuals with poor HR-QoL, i.e. those scoring below the domain and sex specific cut-off value derived from the normal weight population. Logistic regression analysis was used to calculate the probability of having poor domain scores according to the conditions under study. Results Higher grades of obesity and the additional presence of T2D were associated with lower HR-QoL, particularly in the domains physical functioning (men: odds ratios (ORs) 1.48–11.34, P<0.005, and women: ORs 1.66–5.05, P<0.001) and general health (men: ORs 1.44–3.07, P<0.005, and women: ORs 1.36–3.73, P<0.001). A higher percentage of obese individuals with MetS had a poor HR-QoL than those without MetS. Furthermore, we observed a linear trend between inflammation and the percentage of obese individuals with poor scores on the HR-QoL domains. Individuals with MetS were more likely to have poor scores in the domains general health, vitality, social functioning and role limitations due to emotional problems. Obese women with increased inflammation levels were more likely to have poor scores on all domains except role limitations due to emotional problems and mental health. Conclusions The impact of obesity on an individual’s quality of life is enhanced by grade of obesity, T2D, MetS and inflammation and are mainly related to reduced physical health. The mental well-being is less often impaired. PMID:26474291

Regulation of Human γδ T Cells by BTN3A1 Protein Stability and ATP-Binding Cassette Transporters

PubMed Central

Rhodes, David A.; Chen, Hung-Chang; Williamson, James C.; Hill, Alfred; Yuan, Jack; Smith, Sam; Rhodes, Harriet; Trowsdale, John; Lehner, Paul J.; Herrmann, Thomas; Eberl, Matthias

2018-01-01

Activation of human Vγ9/Vδ2 T cells by “phosphoantigens” (pAg), the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP) and the endogenous isoprenoid intermediate isopentenyl pyrophosphate, requires expression of butyrophilin BTN3A molecules by presenting cells. However, the precise mechanism of activation of Vγ9/Vδ2 T cells by BTN3A molecules remains elusive. It is not clear what conformation of the three BTN3A isoforms transmits activation signals nor how externally delivered pAg accesses the cytosolic B30.2 domain of BTN3A1. To approach these problems, we studied two HLA haplo-identical HeLa cell lines, termed HeLa-L and HeLa-M, which showed marked differences in pAg-dependent stimulation of Vγ9/Vδ2 T cells. Levels of IFN-γ secretion by Vγ9/Vδ2 T cells were profoundly increased by pAg loading, or by binding of the pan-BTN3A specific agonist antibody CD277 20.1, in HeLa-M compared to HeLa-L cells. IL-2 production from a murine hybridoma T cell line expressing human Vγ9/Vδ2 T cell receptor (TCR) transgenes confirmed that the differential responsiveness to HeLa-L and HeLa-M was TCR dependent. By tissue typing, both HeLa lines were shown to be genetically identical and full-length transcripts of the three BTN3A isoforms were detected in equal abundance with no sequence variation. Expression of BTN3A and interacting molecules, such as periplakin or RhoB, did not account for the functional variation between HeLa-L and HeLa-M cells. Instead, the data implicate a checkpoint controlling BTN3A1 stability and protein trafficking, acting at an early time point in its maturation. In addition, plasma membrane profiling was used to identify proteins upregulated in HMB-PP-treated HeLa-M. ABCG2, a member of the ATP-binding cassette (ABC) transporter family was the most significant candidate, which crucially showed reduced expression in HeLa-L. Expression of a subset of ABC transporters, including ABCA1 and ABCG1, correlated with efficiency of T cell activation by cytokine secretion, although direct evidence of a functional role was not obtained by knockdown experiments. Our findings indicate a link between members of the ABC protein superfamily and the BTN3A-dependent activation of γδ T cells by endogenous and exogenous pAg. PMID:29670629

Botulinum C3 exoenzyme blocks the tyrosine phosphorylation of p125FAK and paxillin induced by bombesin and endothelin.

PubMed

Rankin, S; Morii, N; Narumiya, S; Rozengurt, E

1994-11-14

In this study we examined the role of rho p21 in neuropeptide-stimulated tyrosine phosphorylation. Intact Swiss 3T3 cells were treated with the Clostridium botulinum C3 exoenzyme which specifically ADP ribosylates and inactivates rho p21. C3 exoenzyme treatment of cells caused a marked decrease in both bombesin- and endothelin-stimulated tyrosine phosphorylation of multiple proteins, including p125 focal adhesion kinase (FAK) and paxillin. Our results suggest that rho p21 is a component of the signal transduction pathway linking seven transmembrane domain receptors with tyrosine phosphorylation and cytoskeletal events.

Anisotropic Optical-Response of Eu-doped Yttrium Orthosilicate

NASA Technical Reports Server (NTRS)

Liu, Huimin; Santiago, Miguel; Jia, Weiyi; Zhang, Shoudu

1998-01-01

Eu-doped yttrium orthosilicate (Eu(3+) : Y2SiO5) had been a subject being investigated for coherent time-domain optical memory and information processing applications since its ultraslow optical dephasing was discovered several years ago. In this crystal the weakly allowed (7)F0 - (5)D0 transition of europium ions exhibits a sufficient long dephasing time and no spectral difli.usion on a time scale of several hours at low temperature, thus an information pattern or data can be stored as a population grating in the ground state hyperfine levels. On the other hand, the study on photon-echo relaxation shows that the dephasing time T2 of Eu (3+) and other rare-earth ions doped YAG, YAlO3 strongly depends on the intensity of the excitation pulses. In Eu (3+) :YAlO3, an exponential decay of photon-echo with T2 = 53 microseconds if the excitation pulses are weak (5 vJ/pulse) was observed. However, when the excitation pulses are strong (80 pJ/pulse) they observed a much shortened T2 with a highly nonexponential decay pattern. The conclusion they derived is that the intensity-dependent dephasing rate effects are quite general, and it depends on how much the excitation intensity varies. In this paper we use transient grating formation technique showing that a temporal lattice distortion may only occur along crystal c axis, caused by EU (3+) excitation. At high excitation level the produced exciton in conduction band may also couple to the dynamical lattice relaxation process, giving rise to an apparently much shortened dephasing time.

The electromagnetic modeling of thin apertures using the finite-difference time-domain technique

NASA Technical Reports Server (NTRS)

Demarest, Kenneth R.

1987-01-01

A technique which computes transient electromagnetic responses of narrow apertures in complex conducting scatterers was implemented as an extension of previously developed Finite-Difference Time-Domain (FDTD) computer codes. Although these apertures are narrow with respect to the wavelengths contained within the power spectrum of excitation, this technique does not require significantly more computer resources to attain the increased resolution at the apertures. In the report, an analytical technique which utilizes Babinet's principle to model the apertures is developed, and an FDTD computer code which utilizes this technique is described.

Integrated Optical Transmitter and Receiver

DTIC Science & Technology

1983-02-01

pulses appear. Only one propagating domain is present at any given time, and when one domain is extracted the next one forms at the cathode. The...formation of a propagating domain results in a reduction in current through T the device, while the current increases after a domain is extracted . As a...net * Vb2 i (3.15) where c is the dielectric constant of the material. The transconductance gm is given by g id _ 1 + + 1 2 gm 5= _ 7 isat[(Vgs Vbi)( v

Site-specific crosslinking of 4-thiouridine-modified human tRNA(3Lys) to reverse transcriptase from human immunodeficiency virus type I.

PubMed Central

Mishima, Y; Steitz, J A

1995-01-01

We have mapped specific RNA-protein contacts between human immunodeficiency virus (HIV) type I reverse transcriptase (RT) and its natural primer, human tRNA(3Lys), using a site-specific crosslinking strategy. Four different tRNA(3Lys) constructs with a single 32P-labeled 4-thiouridine (4-thioU) residue at positions -1, 16, 36 or 41 were synthesized. After incubation with RT followed by irradiation, crosslinks were localized to either the p66 or p51 subunit of RT by digestion with nuclease and SDS gel fractionation. 4-thioU at position -1 or 16 transferred label to the p66 subunit almost exclusively (> 90%), whereas position 36 labeled both p66 and p51 (3:1). Position 41 yielded no detectable crosslinks. The region of p66 contacted by position -1 of tRNA(3Lys) was localized to the 203 C-terminal amino acids of RT by CNBr cleavage, whereas a 127 amino acid-CNBr peptide (residues 230-357) from both p66 and p51 was labeled by position 36. Functionality of the 4-thioU-modified tRNA(3Lys)(-1) crosslinked to RT in the presence of an RNA but not a DNA template was demonstrated by the ability of the tRNA to be extended. These results localize the 5' half of the tRNA on the interface between the two RT subunits, closer to the RNase H domain than to the polymerase active site, in accord with previous suggestions. They argue further that a specific binding site for the 5' end of the primer tRNA(3Lys) may exist within the C-terminal portion of the p66 subunit, which could be important for the initiation of reverse transcription. Images PMID:7540137

A histidine-rich linker region in peptidylglycine α-amidating monooxygenase has the properties of a pH sensor.

PubMed

Vishwanatha, Kurutihalli; Bäck, Nils; Mains, Richard E; Eipper, Betty A

2014-05-02

Decreasing luminal pH is thought to play a role in the entry of newly synthesized and endocytosed membrane proteins into secretory granules. The two catalytic domains of peptidylglycine α-amidating monooxygenase (PAM), a type I integral membrane protein, catalyze the sequential reactions that convert peptidyl-Gly substrates into amidated products. We explored the hypothesis that a conserved His-rich cluster (His-Gly-His-His) in the linker region connecting its two catalytic domains senses pH and affects PAM trafficking by mutating these His residues to Ala (Ala-Gly-Ala-Ala; H3A). Purified recombinant wild-type and H3A linker peptides were examined using circular dichroism and tryptophan fluorescence; mutation of the His cluster largely eliminated its pH sensitivity. An enzymatically active PAM protein with the same mutations (PAM-1/H3A) was expressed in HEK293 cells and AtT-20 corticotrope tumor cells. Metabolic labeling followed by immunoprecipitation revealed more rapid loss of newly synthesized PAM-1/H3A than PAM-1; although release of newly synthesized monofunctional PHM/H3A was increased, release of soluble bifunctional PAM/H3A, a product of the endocytic pathway, was decreased. Surface biotinylation revealed rapid loss of PAM-1/H3A, with no detectable return of the mutant protein to secretory granules. Consistent with its altered endocytic trafficking, little PAM-1/H3A was subjected to regulated intramembrane proteolysis followed by release of a small nuclear-targeted cytosolic fragment. AtT-20 cells expressing PAM-1/H3A adopted the morphology of wild-type AtT-20 cells; secretory products no longer accumulated in the trans-Golgi network and secretory granule exocytosis was more responsive to secretagogue.

CPIC: a curvilinear Particle-In-Cell code for plasma-material interaction studies

NASA Astrophysics Data System (ADS)

Delzanno, G.; Camporeale, E.; Moulton, J. D.; Borovsky, J. E.; MacDonald, E.; Thomsen, M. F.

2012-12-01

We present a recently developed Particle-In-Cell (PIC) code in curvilinear geometry called CPIC (Curvilinear PIC) [1], where the standard PIC algorithm is coupled with a grid generation/adaptation strategy. Through the grid generator, which maps the physical domain to a logical domain where the grid is uniform and Cartesian, the code can simulate domains of arbitrary complexity, including the interaction of complex objects with a plasma. At present the code is electrostatic. Poisson's equation (in logical space) can be solved with either an iterative method based on the Conjugate Gradient (CG) or the Generalized Minimal Residual (GMRES) coupled with a multigrid solver used as a preconditioner, or directly with multigrid. The multigrid strategy is critical for the solver to perform optimally or nearly optimally as the dimension of the problem increases. CPIC also features a hybrid particle mover, where the computational particles are characterized by position in logical space and velocity in physical space. The advantage of a hybrid mover, as opposed to more conventional movers that move particles directly in the physical space, is that the interpolation of the particles in logical space is straightforward and computationally inexpensive, since one does not have to track the position of the particle. We will present our latest progress on the development of the code and document the code performance on standard plasma-physics tests. Then we will present the (preliminary) application of the code to a basic dynamic-charging problem, namely the charging and shielding of a spherical spacecraft in a magnetized plasma for various level of magnetization and including the pulsed emission of an electron beam from the spacecraft. The dynamical evolution of the sheath and the time-dependent current collection will be described. This study is in support of the ConnEx mission concept to use an electron beam from a magnetospheric spacecraft to trace magnetic field lines from the magnetosphere to the ionosphere [2]. [1] G.L. Delzanno, E. Camporeale, "CPIC: a new Particle-in-Cell code for plasma-material interaction studies", in preparation (2012). [2] J.E. Borovsky, D.J. McComas, M.F. Thomsen, J.L. Burch, J. Cravens, C.J. Pollock, T.E. Moore, and S.B. Mende, "Magnetosphere-Ionosphere Observatory (MIO): A multisatellite mission designed to solve the problem of what generates auroral arcs," Eos. Trans. Amer. Geophys. Union 79 (45), F744 (2000).

Amyloid-like assembly of the low complexity domain of yeast Nab3.

PubMed

O'Rourke, Thomas W; Loya, Travis J; Head, PamelaSara E; Horton, John R; Reines, Daniel

2015-01-01

Termination of transcription of short non-coding RNAs is carried out in yeast by the Nab3-Nrd1-Sen1 complex. Nab3 and Nrd1 are hnRNP-like proteins that dimerize and bind RNA with sequence specificity. We show here that an essential region of Nab3 that is predicted to be prion-like based upon its sequence bias, formed amyloid-like filaments. A similar region from Nrd1 also assembled into filaments in vitro. The purified Nab3 domain formed a macroscopic gel whose lattice organization was observed by X-ray fiber diffraction. Filaments were resistant to dissociation in anionic detergent, bound the fluorescent dye thioflavin T, and showed a β-sheet rich structure by circular dichroism spectroscopy, similar to human amyloid β which served as a reference amyloid. A version of the Nab3 domain with a mutation that impairs its termination function, also formed fibers as observed by electron microscopy. Using a protein fragment interaction assay, the purified Nab3 domain was seen to interact with itself in living yeast. A similar observation was made for full length Nab3. These results suggest that the Nab3 and Nrd1 RNA-binding proteins can attain a complex polymeric form and raise the possibility that this property is important for organizing their functional state during termination. These findings are congruent with recent work showing that RNA binding proteins with low complexity domains form a dynamic subcellular matrix in which RNA metabolism takes place but can also aberrantly yield pathological aggregated particles.

Molecular dynamics simulations of human tRNA Lys,3 UUU: the role of modified bases in mRNA recognition.

PubMed

McCrate, Nina E; Varner, Mychel E; Kim, Kenneth I; Nagan, Maria C

2006-01-01

Accuracy in translation of the genetic code into proteins depends upon correct tRNA-mRNA recognition in the context of the ribosome. In human tRNA(Lys,3)UUU three modified bases are present in the anticodon stem-loop--2-methylthio-N6-threonylcarbamoyladenosine at position 37 (ms2t6A37), 5-methoxycarbonylmethyl-2-thiouridine at position 34 (mcm5s2U34) and pseudouridine (psi) at position 39--two of which, ms2t6A37 and mcm5s2U34, are required to achieve wild-type binding activity of wild-type human tRNA(Lys,3)UUU [C. Yarian, M. Marszalek, E. Sochacka, A. Malkiewicz, R. Guenther, A. Miskiewicz and P. F. Agris (2000) Biochemistry, 39, 13390-13395]. Molecular dynamics simulations of nine tRNA anticodon stem-loops with different combinations of nonstandard bases were performed. The wild-type simulation exhibited a canonical anticodon stair-stepped conformation. The ms2t6 modification at position 37 is required for maintenance of this structure and reduces solvent accessibility of U36. Ms2t6A37 generally hydrogen bonds across the loop and may prevent U36 from rotating into solution. A water molecule does coordinate to psi39 most of the simulation time but weakly, as most of the residence lifetimes are <40 ps.

Expression of Innate Immunity Genes in Epithelial Cells of Hypertrophic Adenoids with and without Pediatric Chronic Rhinosinusitis: A Preliminary Report

PubMed Central

Qu, Xiao-Peng; Huang, Zhen-Xiao; Sun, Yan; Ye, Ting; Cui, Shun-Jiu; Huang, Qian; Ma, Li-Jing; Yang, Qing-Wen; Wang, Hong; Fan, Er-Zhong; Li, Ying; Zhang, Liang; Zhou, Bing

2015-01-01

Background: Adenoid hypertrophy (AH) is associated with pediatric chronic rhinosinusitis (pCRS), but its role in the inflammatory process of pCRS is unclear. It is thought that innate immunity gene expression is disrupted in the epithelium of patients with chronic rhinosinusitis (CRS), including antimicrobial peptides and pattern recognition receptors (PRRs). The aim of this preliminary study was to detect the expression of innate immunity genes in epithelial cells of hypertrophic adenoids with and without pCRS to better understand their role in pCRS. Methods: Nine pCRS patients and nine simple AH patients undergoing adenoidectomy were recruited for the study. Adenoidal epithelium was isolated, and real-time quantitative polymerase chain reaction (RT-qPCR) was employed to measure relative expression levels of the following messenger RNAs in hypertrophic adenoid epithelial cells of pediatric patients with and without CRS: Human β-defensin (HBD) 2 and 3, surfactant protein (SP)-A and D, toll-like receptors 1–10, nucleotide-binding oligomerization domain (NOD)-like receptors NOD 1, NOD 2, and NACHT, LRR and PYD domains-containing protein 3, retinoic acid-induced gene 1, melanoma differentiation-associated gene 5, and nuclear factor-κB (NF-κB). RT-qPCR data from two groups were analyzed by independent sample t-tests and Mann-Whitney U-tests. Results: The relative expression of SP-D in adenoidal epithelium of pCRS group was significantly lower than that in AH group (pCRS 0.73 ± 0.10 vs. AH 1.21 ± 0.15; P = 0.0173, t = 2.654). The relative expression levels of all tested PRRs and NF-κB, as well as HBD-2, HBD-3, and SP-A, showed no statistically significant differences in isolated adenoidal epithelium between pCRS group and AH group. Conclusions: Down-regulated SP-D levels in adenoidal epithelium may contribute to the development of pCRS. PRRs, however, are unlikely to play a significant role in the inflammatory process of pCRS. PMID:26521790

Novel pathogenic mutations and skin biopsy analysis in Knobloch syndrome

PubMed Central

Suzuki, Oscar; Kague, Erika; Bagatini, Kelly; Tu, Hongmin; Heljasvaara, Ritva; Carvalhaes, Lorenza; Gava, Elisandra; de Oliveira, Gisele; Godoi, Paulo; Oliva, Glaucius; Kitten, Gregory; Pihlajaniemi, Taina; Passos-Bueno, Maria-Rita

2009-01-01

Purpose To facilitate future diagnosis of Knobloch syndrome (KS) and better understand its etiology, we sought to identify not yet described COL18A1 mutations in KS patients. In addition, we tested whether mutations in this gene lead to absence of the COL18A1 gene product and attempted to better characterize the functional effect of a previously reported missense mutation. Methods Direct sequencing of COL18A1 exons was performed in KS patients from four unrelated pedigrees. We used immunofluorescent histochemistry in skin biopsies to evaluate the presence of type XVIII collagen in four KS patients carrying two already described mutations: c.3277C>T, a nonsense mutation, and c.3601G>A, a missense mutation. Furthermore, we determined the binding properties of the mutated endostatin domain p.A1381T (c.3601G>A) to extracellular matrix proteins using ELISA and surface plasmon resonance assays. Results We identified four novel mutations in COL18A1, including a large deletion involving exon 41. Skin biopsies from KS patients revealed lack of type XVIII collagen in epithelial basement membranes and blood vessels. We also found a reduced affinity of p.A1381T endostatin to some extracellular matrix components. Conclusions COL18A1 mutations involved in Knobloch syndrome have a distribution bias toward the coding exons of the C-terminal end. Large deletions must also be considered when point mutations are not identified in patients with characteristic KS phenotype. We report, for the first time, lack of type XVIII collagen in KS patients by immunofluorescent histochemistry in skin biopsy samples. As a final point, we suggest the employment of this technique as a preliminary and complementary test for diagnosis of KS in cases when mutation screening either does not detect mutations or reveals mutations of uncertain effect, such as the p.A1381T change. PMID:19390655

Novel pathogenic mutations and skin biopsy analysis in Knobloch syndrome.

PubMed

Suzuki, Oscar; Kague, Erika; Bagatini, Kelly; Tu, Hongmin; Heljasvaara, Ritva; Carvalhaes, Lorenza; Gava, Elisandra; de Oliveira, Gisele; Godoi, Paulo; Oliva, Glaucius; Kitten, Gregory; Pihlajaniemi, Taina; Passos-Bueno, Maria-Rita

2009-01-01

To facilitate future diagnosis of Knobloch syndrome (KS) and better understand its etiology, we sought to identify not yet described COL18A1 mutations in KS patients. In addition, we tested whether mutations in this gene lead to absence of the COL18A1 gene product and attempted to better characterize the functional effect of a previously reported missense mutation. Direct sequencing of COL18A1 exons was performed in KS patients from four unrelated pedigrees. We used immunofluorescent histochemistry in skin biopsies to evaluate the presence of type XVIII collagen in four KS patients carrying two already described mutations: c.3277C>T, a nonsense mutation, and c.3601G>A, a missense mutation. Furthermore, we determined the binding properties of the mutated endostatin domain p.A1381T (c.3601G>A) to extracellular matrix proteins using ELISA and surface plasmon resonance assays. We identified four novel mutations in COL18A1, including a large deletion involving exon 41. Skin biopsies from KS patients revealed lack of type XVIII collagen in epithelial basement membranes and blood vessels. We also found a reduced affinity of p.A1381T endostatin to some extracellular matrix components. COL18A1 mutations involved in Knobloch syndrome have a distribution bias toward the coding exons of the C-terminal end. Large deletions must also be considered when point mutations are not identified in patients with characteristic KS phenotype. We report, for the first time, lack of type XVIII collagen in KS patients by immunofluorescent histochemistry in skin biopsy samples. As a final point, we suggest the employment of this technique as a preliminary and complementary test for diagnosis of KS in cases when mutation screening either does not detect mutations or reveals mutations of uncertain effect, such as the p.A1381T change.

Neuropeptides of the beetle, Tenebrio molitor identified using MALDI-TOF mass spectrometry and deduced sequences from the Tribolium castaneum genome.

PubMed

Weaver, Robert J; Audsley, Neil

2008-02-01

Four neuropeptides were identified from the brain and corpora cardiaca-corpora allata (CC-CA) of the mealworm beetle Tenebrio molitor using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and information derived from the genome of the red flour beetle, Tribolium castaneum. Leucomyosuppressin (a FLRFamide), previously associated with cockroaches, but also subsequently identified from honey bee seen as a prominent peptide in both brain and CC-CA of T.molitor. A coding sequence for this peptide is found in the genome of T. castaneum. In addition, three FXPRLamides (pyrokinins), provisionally Tenmo-PK-1, Tenmo-PK-2 and Tenmo-PK-3 (HVVNFTPRLamide, SPPFAPRLamide, HL(I)SPFSPRLamide) were identified in both CC-CA and brain of T. molitor, again on the basis of predicted occurrence or similarity in T. castaneum. The sequence of Tenmo-PK-2 is the same as the PK-2 of the cockroach, Periplaneta americana. Other peptides readily predicted from the genome of T. castaneum include two AKH/HrTH peptides (Trica-AKH-1; pELNFSTDWamide and Trica-AKH-2; pELNFTPNWamide), the second of which is identical to Pyrap-AKH, an AKH-related peptide (Trica AKH-L; pEVTFSRDWPamide), two CRF-related diuretic factors (Trica-DH 37 and Trica-DH 47), the latter identical to Tenmo-DH 47, a putative antidiuretic factor (Trica-ADFb; LYDDGSYKPHVYGF-OH), two sulfakinin-like peptides (Trica-SK-1; pETSDDY(SO(3))GHLRFamide, and Trica SK-2; GEEPFDDYGHMRFamide), a potential allatostatin-C (Trica-AS; pESRYRQCYFNPISCF-OH), six allatostatin-B/myoinhibitory peptides (Trica-AST-B-1,2,3,4,5 & 6; DWNKDLHIWamide, GWNNLHEGWamide, AWQSLQSGWamide, NWGQFHGGWamide, SKWDNFRGSWamide, EPAWSNLGIWamide), an allatotropin-like peptide (Trica-ATL; GIEALKYHNMDLGTARGYamide), four 'CAPA'-related peptides (Trica-CAPA-1,2,3,4; NKLASVYALTPSLRVamide, RIGKMVSFPRIamide, PGANSGGMWFGPRLamide, SENFTPWAYIILNGEAPIIREVHYSPRLamide), proctolin (RYLPT), a potential SIFamide (Trica-SIFa; TYRKPPFNGSIFamide), an arginine-vasopressin-related peptide (Trica-AVP; CLITNCPRGamide) and an ITP-related peptide (Trica-ITP). No evidence was found for the presence of 'A' allatostatins (Y/FxFGLamides) or corazonin, either in T. molitor, or in the genome of T. castaneum.

The Argonaute CSR-1 and its 22G-RNA cofactors are required for holocentric chromosome segregation.

PubMed

Claycomb, Julie M; Batista, Pedro J; Pang, Ka Ming; Gu, Weifeng; Vasale, Jessica J; van Wolfswinkel, Josien C; Chaves, Daniel A; Shirayama, Masaki; Mitani, Shohei; Ketting, René F; Conte, Darryl; Mello, Craig C

2009-10-02

RNAi-related pathways regulate diverse processes, from developmental timing to transposon silencing. Here, we show that in C. elegans the Argonaute CSR-1, the RNA-dependent RNA polymerase EGO-1, the Dicer-related helicase DRH-3, and the Tudor-domain protein EKL-1 localize to chromosomes and are required for proper chromosome segregation. In the absence of these factors chromosomes fail to align at the metaphase plate and kinetochores do not orient to opposing spindle poles. Surprisingly, the CSR-1-interacting small RNAs (22G-RNAs) are antisense to thousands of germline-expressed protein-coding genes. Nematodes assemble holocentric chromosomes in which continuous kinetochores must span the expressed domains of the genome. We show that CSR-1 interacts with chromatin at target loci but does not downregulate target mRNA or protein levels. Instead, our findings support a model in which CSR-1 complexes target protein-coding domains to promote their proper organization within the holocentric chromosomes of C. elegans.

Identification of a Novel GJA8 (Cx50) Point Mutation Causes Human Dominant Congenital Cataracts

NASA Astrophysics Data System (ADS)

Ge, Xiang-Lian; Zhang, Yilan; Wu, Yaming; Lv, Jineng; Zhang, Wei; Jin, Zi-Bing; Qu, Jia; Gu, Feng

2014-02-01

Hereditary cataracts are clinically and genetically heterogeneous lens diseases that cause a significant proportion of visual impairment and blindness in children. Human cataracts have been linked with mutations in two genes, GJA3 and GJA8, respectively. To identify the causative mutation in a family with hereditary cataracts, family members were screened for mutations by PCR for both genes. Sequencing the coding regions of GJA8, coding for connexin 50, revealed a C > A transversion at nucleotide 264, which caused p.P88T mutation. To dissect the molecular consequences of this mutation, plasmids carrying wild-type and mutant mouse ORFs of Gja8 were generated and ectopically expressed in HEK293 cells and human lens epithelial cells, respectively. The recombinant proteins were assessed by confocal microscopy and Western blotting. The results demonstrate that the molecular consequences of the p.P88T mutation in GJA8 include changes in connexin 50 protein localization patterns, accumulation of mutant protein, and increased cell growth.

Modern gyrokinetic particle-in-cell simulation of fusion plasmas on top supercomputers

DOE PAGES

Wang, Bei; Ethier, Stephane; Tang, William; ...

2017-06-29

The Gyrokinetic Toroidal Code at Princeton (GTC-P) is a highly scalable and portable particle-in-cell (PIC) code. It solves the 5D Vlasov-Poisson equation featuring efficient utilization of modern parallel computer architectures at the petascale and beyond. Motivated by the goal of developing a modern code capable of dealing with the physics challenge of increasing problem size with sufficient resolution, new thread-level optimizations have been introduced as well as a key additional domain decomposition. GTC-P's multiple levels of parallelism, including inter-node 2D domain decomposition and particle decomposition, as well as intra-node shared memory partition and vectorization have enabled pushing the scalability ofmore » the PIC method to extreme computational scales. In this paper, we describe the methods developed to build a highly parallelized PIC code across a broad range of supercomputer designs. This particularly includes implementations on heterogeneous systems using NVIDIA GPU accelerators and Intel Xeon Phi (MIC) co-processors and performance comparisons with state-of-the-art homogeneous HPC systems such as Blue Gene/Q. New discovery science capabilities in the magnetic fusion energy application domain are enabled, including investigations of Ion-Temperature-Gradient (ITG) driven turbulence simulations with unprecedented spatial resolution and long temporal duration. Performance studies with realistic fusion experimental parameters are carried out on multiple supercomputing systems spanning a wide range of cache capacities, cache-sharing configurations, memory bandwidth, interconnects and network topologies. These performance comparisons using a realistic discovery-science-capable domain application code provide valuable insights on optimization techniques across one of the broadest sets of current high-end computing platforms worldwide.« less

Modern gyrokinetic particle-in-cell simulation of fusion plasmas on top supercomputers

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

Wang, Bei; Ethier, Stephane; Tang, William

The Gyrokinetic Toroidal Code at Princeton (GTC-P) is a highly scalable and portable particle-in-cell (PIC) code. It solves the 5D Vlasov-Poisson equation featuring efficient utilization of modern parallel computer architectures at the petascale and beyond. Motivated by the goal of developing a modern code capable of dealing with the physics challenge of increasing problem size with sufficient resolution, new thread-level optimizations have been introduced as well as a key additional domain decomposition. GTC-P's multiple levels of parallelism, including inter-node 2D domain decomposition and particle decomposition, as well as intra-node shared memory partition and vectorization have enabled pushing the scalability ofmore » the PIC method to extreme computational scales. In this paper, we describe the methods developed to build a highly parallelized PIC code across a broad range of supercomputer designs. This particularly includes implementations on heterogeneous systems using NVIDIA GPU accelerators and Intel Xeon Phi (MIC) co-processors and performance comparisons with state-of-the-art homogeneous HPC systems such as Blue Gene/Q. New discovery science capabilities in the magnetic fusion energy application domain are enabled, including investigations of Ion-Temperature-Gradient (ITG) driven turbulence simulations with unprecedented spatial resolution and long temporal duration. Performance studies with realistic fusion experimental parameters are carried out on multiple supercomputing systems spanning a wide range of cache capacities, cache-sharing configurations, memory bandwidth, interconnects and network topologies. These performance comparisons using a realistic discovery-science-capable domain application code provide valuable insights on optimization techniques across one of the broadest sets of current high-end computing platforms worldwide.« less

New-Generation Laser-lithographed Dual-Axis Magnetically Assisted Remote-controlled Endovascular Catheter for Interventional MR Imaging: In Vitro Multiplanar Navigation at 1.5 T and 3 T versus X-ray Fluoroscopy.

PubMed

Moftakhar, Parham; Lillaney, Prasheel; Losey, Aaron D; Cooke, Daniel L; Martin, Alastair J; Thorne, Bradford R H; Arenson, Ronald L; Saeed, Maythem; Wilson, Mark W; Hetts, Steven W

2015-12-01

To assess the feasibility of multiplanar vascular navigation with a new magnetically assisted remote-controlled (MARC) catheter with real-time magnetic resonance (MR) imaging at 1.5 T and 3 T and to compare it with standard x-ray guidance in simulated endovascular catheterization procedures. A 1.6-mm-diameter custom clinical-grade microcatheter prototype with lithographed double-saddle coils at the distal tip was deflected with real-time MR imaging. Two inexperienced operators and two experienced operators catheterized anteroposterior (celiac, superior mesenteric, and inferior mesenteric arteries) and mediolateral (renal arteries) branch vessels in a cryogel abdominal aortic phantom. This was repeated with conventional x-ray fluoroscopy by using clinical catheters and guidewires. Mean procedure times and percentage success data were analyzed with linear mixed-effects regression. The MARC catheter tip was visible at 1.5 T and 3 T. Among inexperienced operators, MARC MR imaging guidance was not statistically different from x-ray guidance at 1.5 T (67% successful vessel selection turns with MR imaging vs 76% with x-ray guidance, P = .157) and at 3 T (75% successful turns with MR imaging vs 76% with x-ray guidance, P = .869). Experienced operators were more successful in catheterizing vessels with x-ray guidance (98% success within 60 seconds) than with 1.5-T (65%, P < .001) or 3-T (75%) MR imaging. Among inexperienced operators, mean procedure time was nearly equivalent by using MR imaging (31 seconds) and x-ray guidance (34 seconds, P = .436). Among experienced operators, catheterization was faster with x-ray guidance (20 seconds) compared with 1.5-T MR imaging (42 seconds, P < .001), but MARC guidance improved at 3 T (31 seconds). MARC MR imaging guidance at 3 T was not significantly different from x-ray guidance for the celiac (P = .755), superior mesenteric (P = .358), and inferior mesenteric (P = .065) arteries. Multiplanar navigation with a new MARC catheter with real-time MR imaging at 1.5 T and 3 T is feasible and comparable to x-ray guidance for anteroposterior vessels at 3 T in a vascular phantom.

New-Generation Laser-lithographed Dual-Axis Magnetically Assisted Remote-controlled Endovascular Catheter for Interventional MR Imaging: In Vitro Multiplanar Navigation at 1.5 T and 3 T versus X-ray Fluoroscopy

PubMed Central

Moftakhar, Parham; Lillaney, Prasheel; Losey, Aaron D.; Cooke, Daniel L.; Martin, Alastair J.; Thorne, Bradford R. H.; Arenson, Ronald L.; Saeed, Maythem; Wilson, Mark W.

2015-01-01

Purpose To assess the feasibility of multiplanar vascular navigation with a new magnetically assisted remote-controlled (MARC) catheter with real-time magnetic resonance (MR) imaging at 1.5 T and 3 T and to compare it with standard x-ray guidance in simulated endovascular catheterization procedures. Materials and Methods A 1.6-mm–diameter custom clinical-grade microcatheter prototype with lithographed double-saddle coils at the distal tip was deflected with real-time MR imaging. Two inexperienced operators and two experienced operators catheterized anteroposterior (celiac, superior mesenteric, and inferior mesenteric arteries) and mediolateral (renal arteries) branch vessels in a cryogel abdominal aortic phantom. This was repeated with conventional x-ray fluoroscopy by using clinical catheters and guidewires. Mean procedure times and percentage success data were analyzed with linear mixed-effects regression. Results The MARC catheter tip was visible at 1.5 T and 3 T. Among inexperienced operators, MARC MR imaging guidance was not statistically different from x-ray guidance at 1.5 T (67% successful vessel selection turns with MR imaging vs 76% with x-ray guidance, P = .157) and at 3 T (75% successful turns with MR imaging vs 76% with x-ray guidance, P = .869). Experienced operators were more successful in catheterizing vessels with x-ray guidance (98% success within 60 seconds) than with 1.5-T (65%, P < .001) or 3-T (75%) MR imaging. Among inexperienced operators, mean procedure time was nearly equivalent by using MR imaging (31 seconds) and x-ray guidance (34 seconds, P = .436). Among experienced operators, catheterization was faster with x-ray guidance (20 seconds) compared with 1.5-T MR imaging (42 seconds, P < .001), but MARC guidance improved at 3 T (31 seconds). MARC MR imaging guidance at 3 T was not significantly different from x-ray guidance for the celiac (P = .755), superior mesenteric (P = .358), and inferior mesenteric (P = .065) arteries. Conclusion Multiplanar navigation with a new MARC catheter with real-time MR imaging at 1.5 T and 3 T is feasible and comparable to x-ray guidance for anteroposterior vessels at 3 T in a vascular phantom. © RSNA, 2015 Online supplemental material is available for this article. PMID:26030659

System and method for constructing filters for detecting signals whose frequency content varies with time

DOEpatents

Qian, S.; Dunham, M.E.

1996-11-12

A system and method are disclosed for constructing a bank of filters which detect the presence of signals whose frequency content varies with time. The present invention includes a novel system and method for developing one or more time templates designed to match the received signals of interest and the bank of matched filters use the one or more time templates to detect the received signals. Each matched filter compares the received signal x(t) with a respective, unique time template that has been designed to approximate a form of the signals of interest. The robust time domain template is assumed to be of the order of w(t)=A(t)cos(2{pi}{phi}(t)) and the present invention uses the trajectory of a joint time-frequency representation of x(t) as an approximation of the instantaneous frequency function {phi}{prime}(t). First, numerous data samples of the received signal x(t) are collected. A joint time frequency representation is then applied to represent the signal, preferably using the time frequency distribution series. The joint time-frequency transformation represents the analyzed signal energy at time t and frequency f, P(t,f), which is a three-dimensional plot of time vs. frequency vs. signal energy. Then P(t,f) is reduced to a multivalued function f(t), a two dimensional plot of time vs. frequency, using a thresholding process. Curve fitting steps are then performed on the time/frequency plot, preferably using Levenberg-Marquardt curve fitting techniques, to derive a general instantaneous frequency function {phi}{prime}(t) which best fits the multivalued function f(t). Integrating {phi}{prime}(t) along t yields {phi}{prime}(t), which is then inserted into the form of the time template equation. A suitable amplitude A(t) is also preferably determined. Once the time template has been determined, one or more filters are developed which each use a version or form of the time template. 7 figs.

Resting and postexercise heart rate variability in professional handball players.

PubMed

Kayacan, Yildirim; Yildiz, Sedat

2016-03-01

The aim of this study was to evaluate heart rate variability (HRV) in professional handball players during rest and following a 5 min mild jogging exercise. For that purpose, electrocardiogram (ECG) of male handball players (N.=12, mean age 25±3.95 years) and sedentary controls (N.=14, mean age 23.5±2.95 years) were recorded for 5 min at rest and just after 5 min of mild jogging. ECGs were recorded and following HRV parameters were calculated: time-domain variables such as heart rate (HR), average normal-to-normal RR intervals, standard deviation of normal-to-normal RR intervals, square root of the mean of the squares of differences between adjacent NN intervals, percentage of differences between adjacent NN intervals that are greater than 50 milliseconds (pNN50), and frequency-domain variables such as very low frequency, low (LF) and high frequency (HF) of the power and LF/HF ratio. Unpaired t-test was used to find out differences among groups while paired t-test was used for comparison of each group for pre- and postjogging HRV. Pearson correlations were carried out to find out the relationships between the parameters. Blood pressures were not different between handball players and sedentary controls but exercise increased systolic blood pressure (P<0.01). HR was increased with exercise (P<0.001) and was slower in handball players (P<0.01). QTc was increased with exercise (P<0.001) and was higher in handball players (P<0.001). Exercise decreased pNN50 values in both groups but LF/HF ratio increased only in sedentary subjects. In conclusion, results of the HRV parameters show that sympathovagal balance does not appear to change in handball players in response to a mild, short-time (5 min) jogging exercise. However, in sedentary subjects, either the sympathetic regulation of the autonomous nervous system increased or vagal withdrawal occurred.

Slow dynamics in protein fluctuations revealed by time-structure based independent component analysis: The case of domain motions

NASA Astrophysics Data System (ADS)

Naritomi, Yusuke; Fuchigami, Sotaro

2011-02-01

Protein dynamics on a long time scale was investigated using all-atom molecular dynamics (MD) simulation and time-structure based independent component analysis (tICA). We selected the lysine-, arginine-, ornithine-binding protein (LAO) as a target protein and focused on its domain motions in the open state. A MD simulation of the LAO in explicit water was performed for 600 ns, in which slow and large-amplitude domain motions of the LAO were observed. After extracting domain motions by rigid-body domain analysis, the tICA was applied to the obtained rigid-body trajectory, yielding slow modes of the LAO's domain motions in order of decreasing time scale. The slowest mode detected by the tICA represented not a closure motion described by a largest-amplitude mode determined by the principal component analysis but a twist motion with a time scale of tens of nanoseconds. The slow dynamics of the LAO were well described by only the slowest mode and were characterized by transitions between two basins. The results show that tICA is promising for describing and analyzing slow dynamics of proteins.

Slow dynamics in protein fluctuations revealed by time-structure based independent component analysis: the case of domain motions.

PubMed

Naritomi, Yusuke; Fuchigami, Sotaro

2011-02-14

Protein dynamics on a long time scale was investigated using all-atom molecular dynamics (MD) simulation and time-structure based independent component analysis (tICA). We selected the lysine-, arginine-, ornithine-binding protein (LAO) as a target protein and focused on its domain motions in the open state. A MD simulation of the LAO in explicit water was performed for 600 ns, in which slow and large-amplitude domain motions of the LAO were observed. After extracting domain motions by rigid-body domain analysis, the tICA was applied to the obtained rigid-body trajectory, yielding slow modes of the LAO's domain motions in order of decreasing time scale. The slowest mode detected by the tICA represented not a closure motion described by a largest-amplitude mode determined by the principal component analysis but a twist motion with a time scale of tens of nanoseconds. The slow dynamics of the LAO were well described by only the slowest mode and were characterized by transitions between two basins. The results show that tICA is promising for describing and analyzing slow dynamics of proteins.

New optimal asymmetric quantum codes constructed from constacyclic codes

NASA Astrophysics Data System (ADS)

Xu, Gen; Li, Ruihu; Guo, Luobin; Lü, Liangdong

2017-02-01

In this paper, we propose the construction of asymmetric quantum codes from two families of constacyclic codes over finite field 𝔽q2 of code length n, where for the first family, q is an odd prime power with the form 4t + 1 (t ≥ 1 is integer) or 4t - 1 (t ≥ 2 is integer) and n1 = q2+1 2; for the second family, q is an odd prime power with the form 10t + 3 or 10t + 7 (t ≥ 0 is integer) and n2 = q2+1 5. As a result, families of new asymmetric quantum codes [[n,k,dz/dx

Dual phosphorylation of Btk by Akt/protein kinase b provides docking for 14-3-3ζ, regulates shuttling, and attenuates both tonic and induced signaling in B cells.

PubMed

Mohammad, Dara K; Nore, Beston F; Hussain, Alamdar; Gustafsson, Manuela O; Mohamed, Abdalla J; Smith, C I Edvard

2013-08-01

Bruton's tyrosine kinase (Btk) is crucial for B-lymphocyte activation and development. Mutations in the Btk gene cause X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (Xid) in mice. Using tandem mass spectrometry, 14-3-3ζ was identified as a new binding partner and negative regulator of Btk in both B-cell lines and primary B lymphocytes. The activated serine/threonine kinase Akt/protein kinase B (PKB) phosphorylated Btk on two sites prior to 14-3-3ζ binding. The interaction sites were mapped to phosphoserine pS51 in the pleckstrin homology domain and phosphothreonine pT495 in the kinase domain. The double-alanine, S51A/T495A, replacement mutant failed to bind 14-3-3ζ, while phosphomimetic aspartate substitutions, S51D/T495D, caused enhanced interaction. The phosphatidylinositol 3-kinase (PI3-kinase) inhibitor LY294002 abrogated S51/T495 phosphorylation and binding. A newly characterized 14-3-3 inhibitor, BV02, reduced binding, as did the Btk inhibitor PCI-32765 (ibrutinib). Interestingly, in the presence of BV02, phosphorylation of Btk, phospholipase Cγ2, and NF-κB increased strongly, suggesting that 14-3-3 also regulates B-cell receptor (BCR)-mediated tonic signaling. Furthermore, downregulation of 14-3-3ζ elevated nuclear translocation of Btk. The loss-of-function mutant S51A/T495A showed reduced tyrosine phosphorylation and ubiquitination. Conversely, the gain-of-function mutant S51D/T495D exhibited intense tyrosine phosphorylation, associated with Btk ubiquitination and degradation, likely contributing to the termination of BCR signaling. Collectively, this suggests that Btk could become an important new candidate for the general study of 14-3-3-mediated regulation.

Dual Phosphorylation of Btk by Akt/Protein Kinase B Provides Docking for 14-3-3ζ, Regulates Shuttling, and Attenuates both Tonic and Induced Signaling in B Cells

PubMed Central

Nore, Beston F.; Hussain, Alamdar; Gustafsson, Manuela O.; Mohamed, Abdalla J.

2013-01-01

Bruton's tyrosine kinase (Btk) is crucial for B-lymphocyte activation and development. Mutations in the Btk gene cause X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (Xid) in mice. Using tandem mass spectrometry, 14-3-3ζ was identified as a new binding partner and negative regulator of Btk in both B-cell lines and primary B lymphocytes. The activated serine/threonine kinase Akt/protein kinase B (PKB) phosphorylated Btk on two sites prior to 14-3-3ζ binding. The interaction sites were mapped to phosphoserine pS51 in the pleckstrin homology domain and phosphothreonine pT495 in the kinase domain. The double-alanine, S51A/T495A, replacement mutant failed to bind 14-3-3ζ, while phosphomimetic aspartate substitutions, S51D/T495D, caused enhanced interaction. The phosphatidylinositol 3-kinase (PI3-kinase) inhibitor LY294002 abrogated S51/T495 phosphorylation and binding. A newly characterized 14-3-3 inhibitor, BV02, reduced binding, as did the Btk inhibitor PCI-32765 (ibrutinib). Interestingly, in the presence of BV02, phosphorylation of Btk, phospholipase Cγ2, and NF-κB increased strongly, suggesting that 14-3-3 also regulates B-cell receptor (BCR)-mediated tonic signaling. Furthermore, downregulation of 14-3-3ζ elevated nuclear translocation of Btk. The loss-of-function mutant S51A/T495A showed reduced tyrosine phosphorylation and ubiquitination. Conversely, the gain-of-function mutant S51D/T495D exhibited intense tyrosine phosphorylation, associated with Btk ubiquitination and degradation, likely contributing to the termination of BCR signaling. Collectively, this suggests that Btk could become an important new candidate for the general study of 14-3-3-mediated regulation. PMID:23754751

Open Rotor Noise Prediction Methods at NASA Langley- A Technology Review

NASA Technical Reports Server (NTRS)

Farassat, F.; Dunn, Mark H.; Tinetti, Ana F.; Nark, Douglas M.

2009-01-01

Open rotors are once again under consideration for propulsion of the future airliners because of their high efficiency. The noise generated by these propulsion systems must meet the stringent noise standards of today to reduce community impact. In this paper we review the open rotor noise prediction methods available at NASA Langley. We discuss three codes called ASSPIN (Advanced Subsonic-Supersonic Propeller Induced Noise), FW - Hpds (Ffowcs Williams-Hawkings with penetrable data surface) and the FSC (Fast Scattering Code). The first two codes are in the time domain and the third code is a frequency domain code. The capabilities of these codes and the input data requirements as well as the output data are presented. Plans for further improvements of these codes are discussed. In particular, a method based on equivalent sources is outlined to get rid of spurious signals in the FW - Hpds code.

MHD Simulation of the HIT-SI Experiment

NASA Astrophysics Data System (ADS)

Marklin, George

2003-10-01

The Helicity Injected Torus (HIT) experiment at the University of Washington has been reconfigured into a high beta spheromak with steady state AC current drive [1]. Helicity is injected by two half torus Reversed Field Pinches (RFP's) connected to the ends of the cylindrically symmetric flux conserver, rotated by 90 degrees from each other. The RFP's are driven with sinusoidally varying voltage and flux. Each side has its voltage and flux in phase, but is 90 degrees out of phase from the other side. The helicity injection rate, which is proportional to the voltage times the flux, goes like sin(wt)^2 on one side and cos(wt)^2 on the other, making the total injection rate constant in time. The complex multiply connected 3-dimensional geometry of this device make it difficult to simulate with existing codes that typically use a structured mesh. This poster will describe a new 3D MHD simulation code and a new 3D Taylor state code which both use an unstructured finite element mesh. The mesh is generated from a CAD-like description of an arbitrary arrangement of 3D geometrical objects. Taylor states in the HIT-SI geometry will be shown for different combinations of fluxes in the two injectors. MHD simulation results will be shown starting from a Taylor state with uniform density and temperature and continuing through several cycles of time dependent helicity injection. Field line tracing plots will show the quality of the flux surfaces at various stages in the injection cycle. [1] T. R. Jarboe, Fusion Technology, vol. 36, p. 85, 1999

T Cell Responses Induced by Adenoviral Vectored Vaccines Can Be Adjuvanted by Fusion of Antigen to the Oligomerization Domain of C4b-Binding Protein

PubMed Central

Forbes, Emily K.; de Cassan, Simone C.; Llewellyn, David; Biswas, Sumi; Goodman, Anna L.; Cottingham, Matthew G.; Long, Carole A.; Pleass, Richard J.; Hill, Adrian V. S.; Hill, Fergal; Draper, Simon J.

2012-01-01

Viral vectored vaccines have been shown to induce both T cell and antibody responses in animals and humans. However, the induction of even higher level T cell responses may be crucial in achieving vaccine efficacy against difficult disease targets, especially in humans. Here we investigate the oligomerization domain of the α-chain of C4b-binding protein (C4 bp) as a candidate T cell “molecular adjuvant” when fused to malaria antigens expressed by human adenovirus serotype 5 (AdHu5) vectored vaccines in BALB/c mice. We demonstrate that i) C-terminal fusion of an oligomerization domain can enhance the quantity of antigen-specific CD4+ and CD8+ T cell responses induced in mice after only a single immunization of recombinant AdHu5, and that the T cells maintain similar functional cytokine profiles; ii) an adjuvant effect is observed for AdHu5 vectors expressing either the 42 kDa C-terminal domain of Plasmodium yoelii merozoite surface protein 1 (PyMSP142) or the 83 kDa ectodomain of P. falciparum strain 3D7 apical membrane antigen 1 (PfAMA1), but not a candidate 128kDa P. falciparum MSP1 biallelic fusion antigen; iii) following two homologous immunizations of AdHu5 vaccines, antigen-specific T cell responses are further enhanced, however, in both BALB/c mice and New Zealand White rabbits no enhancement of functional antibody responses is observed; and iv) that the T cell adjuvant activity of C4 bp is not dependent on a functional Fc-receptor γ-chain in the host, but is associated with the oligomerization of small (<80 kDa) antigens expressed by recombinant AdHu5. The oligomerization domain of C4 bp can thus adjuvant T cell responses induced by AdHu5 vectors against selected antigens and its clinical utility as well as mechanism of action warrant further investigation. PMID:22984589

New nonbinary quantum codes with larger distance constructed from BCH codes over 𝔽q2

NASA Astrophysics Data System (ADS)

Xu, Gen; Li, Ruihu; Fu, Qiang; Ma, Yuena; Guo, Luobin

2017-03-01

This paper concentrates on construction of new nonbinary quantum error-correcting codes (QECCs) from three classes of narrow-sense imprimitive BCH codes over finite field 𝔽q2 (q ≥ 3 is an odd prime power). By a careful analysis on properties of cyclotomic cosets in defining set T of these BCH codes, the improved maximal designed distance of these narrow-sense imprimitive Hermitian dual-containing BCH codes is determined to be much larger than the result given according to Aly et al. [S. A. Aly, A. Klappenecker and P. K. Sarvepalli, IEEE Trans. Inf. Theory 53, 1183 (2007)] for each different code length. Thus families of new nonbinary QECCs are constructed, and the newly obtained QECCs have larger distance than those in previous literature.

Comparison of a Simple Patched Conic Trajectory Code to Commercially Available Software

NASA Technical Reports Server (NTRS)

AndersonPark, Brooke M.; Wright, Henry S.

2007-01-01

Often in spaceflight proposal development, mission designers must eva luate numerous trajectories as different design factors are investiga ted. Although there are numerous commercial software packages availab le to help develop and analyze trajectories, most take a significant amount of time to develop the trajectory itself, which isn't effectiv e when working on proposals. Thus a new code, PatCon, which is both q uick and easy to use, was developed to aid mission designers to condu ct trade studies on launch and arrival times for any given target pla net. The code is able to run quick analyses, due to the incorporation of the patched conic approximation, to determine the trajectory. PatCon provides a simple but accurate approximation of the four body moti on problem that would be needed to solve any planetary trajectory. P atCon has been compared to a patched conic test case for verification, with limited validation or comparison with other COTS software. This paper describes the patched conic technique and its implementation i n PatCon. A description of the results and comparison of PatCon to ot her more evolved codes such as AGI#s Satellite Tool Kit and JAQAR As trodynamics# Swingby Calculator is provided. The results will include percent differences in values such as C3 numbers, and Vinfinity at a rrival, and other more subjective results such as the time it takes to build the simulation, and actual calculation time.

Acoustic wave simulation using an overset grid for the global monitoring system

NASA Astrophysics Data System (ADS)

Kushida, N.; Le Bras, R.

2017-12-01

The International Monitoring System of the Comprehensive Nuclear-Test-Ban Treaty Organization (CTBTO) has been monitoring hydro-acoustic and infrasound waves over the globe. Because of the complex natures of the oceans and the atmosphere, computer simulation can play an important role in understanding the observed signals. In this regard, methods which depend on partial differential equations and require minimum modelling, are preferable. So far, to our best knowledge, acoustic wave propagation simulations based on partial differential equations on such a large scale have not been performed (pp 147 - 161 of ref [1], [2]). The main difficulties in building such simulation codes are: (1) considering the inhomogeneity of medium including background flows, (2) high aspect ratio of computational domain, (3) stability during long time integration. To overcome these difficulties, we employ a two-dimensional finite different (FDM) scheme on spherical coordinates with the Yin-Yang overset grid[3] solving the governing equation of acoustic waves introduces by Ostashev et. al.[4]. The comparison with real recording examples in hydro-acoustic will be presented at the conference. [1] Paul C. Etter: Underwater Acoustic Modeling and Simulation, Fourth Edition, CRC Press, 2013. [2] LIAN WANG et. al.: REVIEW OF UNDERWATER ACOUSTIC PROPAGATION MODELS, NPL Report AC 12, 2014. [3] A. Kageyama and T. Sato: "Yin-Yang grid": An overset grid in spherical geometry, Geochem. Geophys. Geosyst., 5, Q09005, 2004. [4] Vladimir E. Ostashev et. al: Equations for finite-difference, time-domain simulation of sound propagation in moving inhomogeneous media and numerical implementation, Acoustical Society of America. DOI: 10.1121/1.1841531, 2005.

Influence of the Helicopter Time Domain Electromagnetic System Off-Time Response by the Transmitter Assembly

NASA Astrophysics Data System (ADS)

Vetrov, A.; Mejzr, I.

2010-12-01

While developing a new Helicopter Time Domain Electromagnetic system (P-THEM), Pico Envirotec Inc (PEI) has studied the effect of the transmitter assembly on the acquired data. The P-THEM system consists of a loop-transmitter assembly, powered by a motor generator, 3-axis coil receiver attached at the midpoint of a tow cable and an additional Z-axis (dB/dt) receiver installed on the rear section of the transmitter loop. The system is towed by a helicopter on a 230 foot long tow cable. The transmitter loop is designed to produce a peak magnetic moment of approximately 250,000 NIA with a base frequency of 30 Hz (adjustable to 25Hz) and a quarter length duty cycle (4 ms on-time). The secondary field acquired with a dB/dt receiver coil consists of a ground response and a system response: SF=Rg+Rsys, where SF - the secondary field, Rg - ground response, Rsys - system response. The system itself, especially the transmitter assembly, being a conductor in an induced magnetic field, creates a magnetic anomaly. The influence of the transmitter assembly anomaly on the received signal depends on the position of the receiver coil against the transmitter, the intensity of on-time pulse and transmitter electro-magnetic properties. At the same time, the ground response acquired with a receiver coil depends on the length and the moment of transmitter pulse, as well as the position and distance of the receiver coil from the ground. This can be for vertical field (Z) receiver coil described as RXz(t)=e(t)pz(t)Rgz(t)+d(t)k(t)j(t)TXz(t), where RXz(t) - receiver response, e(t) - elevation of the receiver over the ground, pz(t) - horizontal projection of the receiver coil, Rgz(t) - vertical component of ground response, d(t) - distance (elevation) between the receiver coil and the transmitter loop, k(t) - the position of the receiver in the transmitter field, j(t) - the transmitter assembly electromagnetic properties, TXz(t) -transmitter field (Primary field on-time, and transmitter assembly response off-time). Changes in the electromagnetic properties of the transmitter loop and mechanical vibrations of the transmitter and receiver are much lower frequency in comparison with the base frequency and can be omitted from consideration of a one cycle length period. The transmitter assembly response has to be subtracted from acquired off-time decay for a correct interpretation of ground response. The transmitter influence is very low when the receiving coil is placed far away. However, the transmitter influence is very important when the receiver is close to the transmitter assembly due to the transmitter anomaly decay which then becomes greater than the ground response. The transmitter assembly off-time response can be registered when the system is flown at a sufficiently high altitude and it is not affected by ground conductors. A number of experiments were conducted to determine the transmitter influence content in the acquired data. The secondary dB/dt receiver installed at different elevations over the transmitter loop in test flights It showed the influence change of the transmitter assembly on the acquired secondary field (OFF-time) dependent upon the distance between the transmitter assembly and the receiver loop.

Identification of RNF213 as a susceptibility gene for moyamoya disease and its possible role in vascular development.

PubMed

Liu, Wanyang; Morito, Daisuke; Takashima, Seiji; Mineharu, Yohei; Kobayashi, Hatasu; Hitomi, Toshiaki; Hashikata, Hirokuni; Matsuura, Norio; Yamazaki, Satoru; Toyoda, Atsushi; Kikuta, Ken-ichiro; Takagi, Yasushi; Harada, Kouji H; Fujiyama, Asao; Herzig, Roman; Krischek, Boris; Zou, Liping; Kim, Jeong Eun; Kitakaze, Masafumi; Miyamoto, Susumu; Nagata, Kazuhiro; Hashimoto, Nobuo; Koizumi, Akio

2011-01-01

Moyamoya disease is an idiopathic vascular disorder of intracranial arteries. Its susceptibility locus has been mapped to 17q25.3 in Japanese families, but the susceptibility gene is unknown. Genome-wide linkage analysis in eight three-generation families with moyamoya disease revealed linkage to 17q25.3 (P<10(-4)). Fine mapping demonstrated a 1.5-Mb disease locus bounded by D17S1806 and rs2280147. We conducted exome analysis of the eight index cases in these families, with results filtered through Ng criteria. There was a variant of p.N321S in PCMTD1 and p.R4810K in RNF213 in the 1.5-Mb locus of the eight index cases. The p.N321S variant in PCMTD1 could not be confirmed by the Sanger method. Sequencing RNF213 in 42 index cases confirmed p.R4810K and revealed it to be the only unregistered variant. Genotyping 39 SNPs around RNF213 revealed a founder haplotype transmitted in 42 families. Sequencing the 260-kb region covering the founder haplotype in one index case did not show any coding variants except p.R4810K. A case-control study demonstrated strong association of p.R4810K with moyamoya disease in East Asian populations (251 cases and 707 controls) with an odds ratio of 111.8 (P = 10(-119)). Sequencing of RNF213 in East Asian cases revealed additional novel variants: p.D4863N, p.E4950D, p.A5021V, p.D5160E, and p.E5176G. Among Caucasian cases, variants p.N3962D, p.D4013N, p.R4062Q and p.P4608S were identified. RNF213 encodes a 591-kDa cytosolic protein that possesses two functional domains: a Walker motif and a RING finger domain. These exhibit ATPase and ubiquitin ligase activities. Although the mutant alleles (p.R4810K or p.D4013N in the RING domain) did not affect transcription levels or ubiquitination activity, knockdown of RNF213 in zebrafish caused irregular wall formation in trunk arteries and abnormal sprouting vessels. We provide evidence suggesting, for the first time, the involvement of RNF213 in genetic susceptibility to moyamoya disease.

Transition from Target to Gaze Coding in Primate Frontal Eye Field during Memory Delay and Memory-Motor Transformation.

PubMed

Sajad, Amirsaman; Sadeh, Morteza; Yan, Xiaogang; Wang, Hongying; Crawford, John Douglas

2016-01-01

The frontal eye fields (FEFs) participate in both working memory and sensorimotor transformations for saccades, but their role in integrating these functions through time remains unclear. Here, we tracked FEF spatial codes through time using a novel analytic method applied to the classic memory-delay saccade task. Three-dimensional recordings of head-unrestrained gaze shifts were made in two monkeys trained to make gaze shifts toward briefly flashed targets after a variable delay (450-1500 ms). A preliminary analysis of visual and motor response fields in 74 FEF neurons eliminated most potential models for spatial coding at the neuron population level, as in our previous study (Sajad et al., 2015). We then focused on the spatiotemporal transition from an eye-centered target code (T; preferred in the visual response) to an eye-centered intended gaze position code (G; preferred in the movement response) during the memory delay interval. We treated neural population codes as a continuous spatiotemporal variable by dividing the space spanning T and G into intermediate T-G models and dividing the task into discrete steps through time. We found that FEF delay activity, especially in visuomovement cells, progressively transitions from T through intermediate T-G codes that approach, but do not reach, G. This was followed by a final discrete transition from these intermediate T-G delay codes to a "pure" G code in movement cells without delay activity. These results demonstrate that FEF activity undergoes a series of sensory-memory-motor transformations, including a dynamically evolving spatial memory signal and an imperfect memory-to-motor transformation.

Structure of Thermotoga maritima Stationary Phase Survival Protein SurE: A Novel Acid Phosphatase

PubMed Central

Zhang, R.-G.; Skarina, T.; Katz, J.E.; Beasley, S.; Khachatryan, A.; Vyas, S.; Arrowsmith, C.H.; Clarke, S.; Edwards, A.; Joachimiak, A.; Savchenko, A.

2009-01-01

Summary Background The rpoS, nlpD, pcm, and surE genes are among many whose expression is induced during the stationary phase of bacterial growth. rpoS codes for the stationary-phase RNA polymerase σ subunit, and nlpD codes for a lipoprotein. The pcm gene product repairs damaged proteins by converting the atypical isoaspartyl residues back to L-aspartyls. The physiological and biochemical functions of surE are unknown, but its importance in stress is supported by the duplication of the surE gene in E. coli subjected to high-temperature growth. The pcm and surE genes are highly conserved in bacteria, archaea, and plants. Results The structure of SurE from Thermotoga maritima was determined at 2.0 Å. The SurE monomer is composed of two domains; a conserved N-terminal domain, a Rossman fold, and a C-terminal oligomerization domain, a new fold. Monomers form a dimer that assembles into a tetramer. Biochemical analysis suggests that SurE is an acid phosphatase, with an optimum pH of 5.5–6.2. The active site was identified in the N-terminal domain through analysis of conserved residues. Structure-based site-directed point mutations abolished phosphatase activity. T. maritima SurE intra- and inter-subunit salt bridges were identified that may explain the SurE thermostability. Conclusions The structure of SurE provided information about the protein’s fold, oligomeric state, and active site. The protein possessed magnesium-dependent acid phosphatase activity, but the physiologically relevant substrate(s) remains to be identified. The importance of three of the assigned active site residues in catalysis was confirmed by site-directed mutagenesis. PMID:11709173

[Effects of lipopolysaccharides from Porphyromonas endodontalis on the expression of MIP-1α in mouse osteoblasts].

PubMed

Yu, Ya-Qiong; Li, Xiao-Lin; Qiu, Li-Hong; Guo, Jia-Jie; Yang, Di; Guo, Yan

2017-06-01

To investigate the effects of lipopolysaccharides(LPS) extracted from Porphyromonas endodontalis(P.e) on the expression of macrophageinflammatoryprotein-1α (MIP-1α) mRNA and protein levels in MC3T3-E1 cells and the influence of curcumin in the process. MC3T3-E1 cells were treated with 20 mg/L P.e-LPS for different times (0-48 h). The expression of MIP-1α mRNA and protein was detected by real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) and enzyme linked immunosorbent assay(ELISA). MC3T3-E1 cells were pretreated with inhibitor of (curcumin) for 1 h, and then treated with 20 mg/L P.e-LPS. The expression of MIP-1α was also detected by real-time RT-PCR and ELISA.Statistical analysis was performed using one-way ANOVA and Dunnett's t test with SPSS 13.0 software package. In the observation time (0-48 h), the impact of 20 P.e-LPS mg/L on induction of MIP-1α in MC3T3-El cells exhibited a time-dependent manner. The expression of MIP-1α mRNA and protein decreased significantly after pretreatment with 10 μmol/L curcumin for 1 h. The results suggest that P.e-LPS may mediate MIP-1α expression in MC3T3-E1 cells, and curcumin has a significant inhibitory effect on this process.

Job Demands, Burnout, and Teamwork in Healthcare Professionals Working in a General Hospital that Was Analysed At Two Points in Time

PubMed Central

Mijakoski, Dragan; Karadzhinska-Bislimovska, Jovanka; Stoleski, Sasho; Minov, Jordan; Atanasovska, Aneta; Bihorac, Elida

2018-01-01

AIM: The purpose of the paper was to assess job demands, burnout, and teamwork in healthcare professionals (HPs) working in a general hospital that was analysed at two points in time with a time lag of three years. METHODS: Time 1 respondents (N = 325) were HPs who participated during the first wave of data collection (2011). Time 2 respondents (N = 197) were HPs from the same hospital who responded at Time 2 (2014). Job demands, burnout, and teamwork were measured with Hospital Experience Scale, Maslach Burnout Inventory, and Hospital Survey on Patient Safety Culture, respectively. RESULTS: Significantly higher scores of emotional exhaustion (21.03 vs. 15.37, t = 5.1, p < 0.001), depersonalization (4.48 vs. 2.75, t = 3.8, p < 0.001), as well as organizational (2.51 vs. 2.34, t = 2.38, p = 0.017), emotional (2.46 vs. 2.25, t = 3.68, p < 0.001), and cognitive (2.82 vs. 2.64, t = 2.68, p = 0.008) job demands were found at Time 2. Teamwork levels were similar at both points in time (Time 1 = 3.84 vs. Time 2 = 3.84, t = 0.043, p = 0.97). CONCLUSION: Actual longitudinal study revealed significantly higher mean values of emotional exhaustion and depersonalization in 2014 that could be explained by significantly increased job demands between analysed points in time. PMID:29731948

Structure of the Pseudomonas aeruginosa Type IVa Pilus Secretin at 7.4 Å.

PubMed

Koo, Jason; Lamers, Ryan P; Rubinstein, John L; Burrows, Lori L; Howell, P Lynne

2016-10-04

Type IVa pili (T4aP) function as bacterial virulence factors. T4aP pass through the outer membranes of Gram-negative bacteria via homo-oligomeric secretins. We present a 7.4 Å cryoelectron microscopy structure of the Pseudomonas aeruginosa PilQ secretin. Peripheral and internal features show that the secretin is composed of 14 subunits with C7 symmetry. The channel is a ribbed cylinder with central peripheral spokes and a central gate closed on the periplasmic side. The structure suggests that during pilus extrusion, the central gate is displaced to the interior walls and that no additional conformational changes are required, as the internal diameter can accommodate the pilus. The N1 domain was resolved, while the N0 and the N-terminal β-domains proposed to bind peptidoglycan were absent in class average images and the final 3D map, indicating a high flexibility. These data provide the highest-resolution structure to date of a T4aP secretin. Copyright © 2016 Elsevier Ltd. All rights reserved.

Association between developmental steps in the organogenesis of the uterine cervix and locoregional progression of cervical cancer: a prospective clinicopathological analysis.

PubMed

Höckel, Michael; Hentschel, Bettina; Horn, Lars-Christian

2014-04-01

Our previous work provided evidence that early cervical cancer is locally confined to the Müllerian compartment that develops in women from the embryonic paramesonephric-mesonephric complex. We aimed to investigate if the concept of tumour permeation within ontogenetic domains is also valid for tumour progression and advanced disease. Starting from Carnegie stage 13, four successive steps in the organogenesis of the human uterine cervix were defined and an ontogenetic staging system for cervical cancer based on organ development was described. Histopathological and clinical data of patients with cervical cancer FIGO stages IB-IVA were raised prospectively from Oct 16, 1999, until Dec 20, 2012, and from March 8, 2000, until April 4, 2013, for two surgical trials of ontogenetic compartment resection without adjuvant radiation at the University of Leipzig (total or extended mesometrial resection [TMMR or EMMR]; and [laterally] extended endopelvic resection [LEER]). The primary endpoints of these trials were pathological resection state and locoregional tumour control. Patients who underwent TMMR and EMMR had follow-up assessment every 3-6 months for 5 years, and yearly thereafter. Patients who had (L)EER, every 3-6 months for 10 years, and yearly thereafter. By analysing the presence of disease within the classified tissues and disease outcome in these patients, and by examining relapse patterns, we were able to observe whether surgical excision within developmental compartments was sufficient for disease control. Survival curves were compared using the log-rank test. The effect of ontogenetic tumour stage and pathological tumour stage on overall survival was assessed by Cox proportional hazard models. The trials are registered as an ongoing observational monocentric study at the University of Leipzig Cancer Centre (ULCC012-13-28012013). 367 patients were included in our analysis. Staged organogenesis of the uterine cervix and progressive local growth of cervical carcinoma occur in the same tissue domains. The neoplasm originating in the uterine cervix, ontogenetic tumour stage 1 (oT1, n=217), permeates successively during its malignant progression the tissues developed from the Müllerian compartment (oT2, n=101), the genital metacompartment (oT3, n=38), and the urogenitorectal metacompartment (oT4, n=11). Ontogenetic staging, when comparing patients with oT1 and oT2 disease to those with oT3 and oT4 disease (hazard ratio 5·9, 95% CI 2·2-15·5; p=0·00036) was a better prognostic indicator for survival than pathological staging when comparing pT1b and pT2a with pT2b and pT4 disease (2·0, 95% CI 0·7-5·5; p=0·170). Resection of the stage-related ontogenetically specified tissue domains and their associated regional lymphoid tissues achieved an R0 resection in 363 (99%) of 367 patients and locoregional tumour control at 5 years was 94% (95% CI 92-97). 13 patients had grade 3 or 4 adverse events, the majority of which were urinary (10, 77%). Cervical cancer infiltrates the adult tissues established during ontogeny, pursuing the developmental steps in retrograde sequence. Clinical translation of these insights into ontogenetic tumour staging and compartment resection holds the potential to improve prognostic assessment and curative treatment. University of Leipzig and Leipzig School of Radical Pelvic Surgery. Copyright © 2014 Elsevier Ltd. All rights reserved.

Molecular and functional characterization of a Taenia adhesion gene family (TAF) encoding potential protective antigens of Taenia saginata oncospheres.

PubMed

Gonzalez, Luis Miguel; Bonay, Pedro; Benitez, Laura; Ferrer, Elizabeth; Harrison, Leslie J S; Parkhouse, R Michael E; Garate, Teresa

2007-02-01

Two clones from an activated Taenia saginata oncosphere cDNA library, Ts45W and Ts45S, were isolated and sequenced. Both of these genes belong to the Taenia ovis 45W gene family. The Ts45W and Ts45S cDNAs are 997- and 1,004-bp-long, each corresponding to 255 amino acids and with theoretical molecular masses of 27.8 and 27.7 kDa, respectively. Southern blot profiles obtained with Ts45W cDNA as a probe suggest that these two genes are members of a multigene family with tandem organization. The full genomic sequence was determined for the Ts45W gene and a new family member, the Ts45W/2 gene. The genomic sequences of the T. saginata Ts45W and Ts45W/2 genes were at least 2.2 kb in length with four exons separated by three introns. Exons 1 and 4 coded for hydrophobic domains, while, importantly, exons 2 and 3 coded for fibronectin homologous domains. These domains are presumably responsible for the demonstrated cell adhesion and, perhaps, the protective nature of this family of molecules and the acronym TAF (Taenia adhesion family) is proposed for this group of genes. We hypothesize that these TAF proteins and another T. saginata-protective antigen, HP6, have evolved the dual functions of facilitating tissue invasion and stimulating protective immunity to first ensure primary infection and subsequently to establish a concomitant protective immunity to protect the host from death or debilitation through superinfection by subsequent infections and thus help ensure parasite survival.

The TDP-43 N-terminal domain structure at high resolution.

PubMed

Mompeán, Miguel; Romano, Valentina; Pantoja-Uceda, David; Stuani, Cristiana; Baralle, Francisco E; Buratti, Emanuele; Laurents, Douglas V

2016-04-01

Transactive response DNA-binding protein 43 kDa (TDP-43) is an RNA transporting and processing protein whose aberrant aggregates are implicated in neurodegenerative diseases. The C-terminal domain of this protein plays a key role in mediating this process. However, the N-terminal domain (residues 1-77) is needed to effectively recruit TDP-43 monomers into this aggregate. In the present study, we report, for the first time, the essentially complete (1) H, (15) N and (13) C NMR assignments and the structure of the N-terminal domain determined on the basis of 26 hydrogen-bond, 60 torsion angle and 1058 unambiguous NOE structural restraints. The structure consists of an α-helix and six β-strands. Two β-strands form a β-hairpin not seen in the ubiquitin fold. All Pro residues are in the trans conformer and the two Cys are reduced and distantly separated on the surface of the protein. The domain has a well defined hydrophobic core composed of F35, Y43, W68, Y73 and 17 aliphatic side chains. The fold is topologically similar to the reported structure of axin 1. The protein is stable and no denatured species are observed at pH 4 and 25 °C. At 4 kcal·mol(-1) , the conformational stability of the domain, as measured by hydrogen/deuterium exchange, is comparable to ubiquitin (6 kcal·mol(-1) ). The β-strands, α-helix, and three of four turns are generally rigid, although the loop formed by residues 47-53 is mobile, as determined by model-free analysis of the (15) N{(1) H}NOE, as well as the translational and transversal relaxation rates. Structural data have been deposited in the Protein Data Bank under accession code: 2n4p. The NMR assignments have been deposited in the BMRB database under access code: 25675. © 2016 Federation of European Biochemical Societies.

Structures of a bifunctional cell wall hydrolase CwlT containing a novel bacterial lysozyme and an NlpC/P60 DL-endopeptidase.

PubMed

Xu, Qingping; Chiu, Hsiu-Ju; Farr, Carol L; Jaroszewski, Lukasz; Knuth, Mark W; Miller, Mitchell D; Lesley, Scott A; Godzik, Adam; Elsliger, Marc-André; Deacon, Ashley M; Wilson, Ian A

2014-01-09

Tn916-like conjugative transposons carrying antibiotic resistance genes are found in a diverse range of bacteria. Orf14 within the conjugation module encodes a bifunctional cell wall hydrolase CwlT that consists of an N-terminal bacterial lysozyme domain (N-acetylmuramidase, bLysG) and a C-terminal NlpC/P60 domain (γ-d-glutamyl-l-diamino acid endopeptidase) and is expected to play an important role in the spread of the transposons. We determined the crystal structures of CwlT from two pathogens, Staphylococcus aureus Mu50 (SaCwlT) and Clostridium difficile 630 (CdCwlT). These structures reveal that NlpC/P60 and LysG domains are compact and conserved modules, connected by a short flexible linker. The LysG domain represents a novel family of widely distributed bacterial lysozymes. The overall structure and the active site of bLysG bear significant similarity to other members of the glycoside hydrolase family 23 (GH23), such as the g-type lysozyme (LysG) and Escherichia coli lytic transglycosylase MltE. The active site of bLysG contains a unique structural and sequence signature (DxxQSSES+S) that is important for coordinating a catalytic water. Molecular modeling suggests that the bLysG domain may recognize glycan in a similar manner to MltE. The C-terminal NlpC/P60 domain contains a conserved active site (Cys-His-His-Tyr) that appears to be specific to murein tetrapeptide. Access to the active site is likely regulated by isomerism of a side chain atop the catalytic cysteine, allowing substrate entry or product release (open state), or catalysis (closed state). © 2013.

BCS-BEC crossover and quantum hydrodynamics in p-wave superfluids with a symmetry of the A1 phase

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

Kagan, M. Yu., E-mail: kagan@kapitza.ras.ru; Efremov, D. V.

2010-03-15

We solve the Leggett equations for the BCS-BEC crossover in a three dimensional resonance p-wave superfluid with the symmetry of the A1 phase. We calculate the sound velocity, the normal density, and the specific heat for the BCS domain ({mu} > 0), for the BEC domain ({mu} < 0), and close to the important point {mu} = 0 in the 100% polarized case. We find the indications of a quantum phase transition close to the point {mu}(T = 0) = 0. Deep in the BCS and BEC domains, the crossover ideas of Leggett, Nozieres, and Schmitt-Rink work quite well. Wemore » discuss the spectrum of orbital waves, the paradox of intrinsic angular momentum and the complicated problem of chiral anomaly in the BCS A1 phase at T = 0. We present two different approaches to the chiral anomaly, based on supersymmetric hydrodynamics and on the formal analogy with the Dirac equation in quantum electrodynamics. We evaluate the damping of nodal fermions due to different decay processes in the superclean case at T = 0 and find that a ballistic regime {omega}{tau} >> 1 occurs. We propose to use aerogel or nonmagnetic impurities to reach the hydrodynamic regime {omega}{tau} << 1 at T = 0. We discuss the concept of the spectral flow and exact cancelations between time derivatives of anomalous and quasiparticle currents in the equation for the total linear momentum conservation. We propose to derive and solve the kinetic equation for the nodal quasiparticles in both the hydrodynamic and ballistic regimes to demonstrate this cancelation explicitly. We briefly discuss the role of the other residual interactions different from damping and invite experimentalists to measure the spectrum and damping of orbital waves in the A phase of {sup 3}He at low temperatures.« less

Truncating variants in the majority of the cytoplasmic domain of PCDH15 are unlikely to cause Usher syndrome 1F.

PubMed

Perreault-Micale, Cynthia; Frieden, Alexander; Kennedy, Caleb J; Neitzel, Dana; Sullivan, Jessica; Faulkner, Nicole; Hallam, Stephanie; Greger, Valerie

2014-11-01

Loss of function variants in the PCDH15 gene can cause Usher syndrome type 1F, an autosomal recessive disease associated with profound congenital hearing loss, vestibular dysfunction, and retinitis pigmentosa. The Ashkenazi Jewish population has an increased incidence of Usher syndrome type 1F (founder variant p.Arg245X accounts for 75% of alleles), yet the variant spectrum in a panethnic population remains undetermined. We sequenced the coding region and intron-exon borders of PCDH15 using next-generation DNA sequencing technology in approximately 14,000 patients from fertility clinics. More than 600 unique PCDH15 variants (single nucleotide changes and small indels) were identified, including previously described pathogenic variants p.Arg3X, p.Arg245X (five patients), p.Arg643X, p.Arg929X, and p.Arg1106X. Novel truncating variants were also found, including one in the N-terminal extracellular domain (p.Leu877X), but all other novel truncating variants clustered in the exon 33 encoded C-terminal cytoplasmic domain (52 patients, 14 variants). One variant was observed predominantly in African Americans (carrier frequency of 2.3%). The high incidence of truncating exon 33 variants indicates that they are unlikely to cause Usher syndrome type 1F even though many remove a large portion of the gene. They may be tolerated because PCDH15 has several alternate cytoplasmic domain exons and differentially spliced isoforms may function redundantly. Effects of some PCDH15 truncating variants were addressed by deep sequencing of a panethnic population. Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Turn Off the TV and Dance! Participation in Culturally Tailored Health Interventions: Implications for Obesity Prevention among Mexican American Girls

PubMed Central

Azevedo, Kathryn J.; Mendoza, Sonia; Fernández, María; Haydel, K. Farish; Fujimoto, Michelle; Tirumalai, Evelyn C.; Robinson, Thomas N.

2014-01-01

Our evaluation study identifies facilitators and barriers to participation among families participating in the treatment arm of Stanford ECHALE. This culturally tailored obesity prevention trial consisted of a combined intervention with two main treatment components: 1) a folkloric dance program; and 2) a screen time reduction curriculum designed for 7–11 year old Latinas and their families. We conducted 83 interviews (40 parents and 43 girls) in participant homes after 6 months of enrollment in the ECHALE trial. The Spradley ethnographic method and NVivo 8.0 were used to code and analyze narrative data. Three domains emerged for understanding participation: 1) family cohesiveness; 2) perceived gains; and 3) culturally relevant program structure. Two domains emerged for non-participation: program requirements and perceived discomforts. Non-parametric, Spearman’s rank correlation coefficients were calculated to assess the relationships with participant attendance data. Sustained participation was most strongly influenced by the domain perceived gains when parents reported better self-esteem, confidence, improved attitude, improved grades, etc. (Spearman r=.45, P=.003). Alternatively, under the domain, perceived discomforts, with subthemes such as child bullying, participation in the combined intervention was inversely associated with attendance (Spearman r=.38, P=.02). Family-centered, school-based, community obesity prevention programs that focus on tangible short-term gains for girls may generate greater participation rates, enhance social capital, and promote community empowerment. These factors can be emphasized in future obesity prevention program design and implementation. (Ethn Dis. 2013; 23[4]:452–461) PMID:24392608

A theoretical study of the H-abstraction reactions from HOI by moist air radiolytic products (H, OH, and O (3P)) and iodine atoms (2P(3/2)).

PubMed

Hammaecher, Catherine; Canneaux, Sébastien; Louis, Florent; Cantrel, Laurent

2011-06-23

The rate constants of the reactions of HOI molecules with H, OH, O ((3)P), and I ((2)P(3/2)) atoms have been estimated over the temperature range 300-2500 K using four different levels of theory. Geometry optimizations and vibrational frequency calculations are performed using MP2 methods combined with two basis sets (cc-pVTZ and 6-311G(d,p)). Single-point energy calculations are performed with the highly correlated ab initio coupled cluster method in the space of single, double, and triple (pertubatively) electron excitations CCSD(T) using the cc-pVTZ, cc-pVQZ, 6-311+G(3df,2p), and 6-311++G(3df,3pd) basis sets. Reaction enthalpies at 0 K were calculated at the CCSD(T)/cc-pVnZ//MP2/cc-pVTZ (n = T and Q), CCSD(T)/6-311+G(3df,2p)//MP2/6-311G(d,p), and CCSD(T)/6-311++G(3df,3pd)//MP2/6-311G(d,p) levels of theory and compared to the experimental values taken from the literature. Canonical transition-state theory with an Eckart tunneling correction is used to predict the rate constants as a function of temperature. The computational procedure has been used to predict rate constants for H-abstraction elementary reactions because there are actually no literature data to which the calculated rate constants can be directly compared. The final objective is to implement kinetics of gaseous reactions in the ASTEC (accident source term evaluation code) program to improve speciation of fission products, which can be transported along the reactor coolant system (RCS) of a pressurized water reactor (PWR) in the case of a severe accident.

Time-domain seismic modeling in viscoelastic media for full waveform inversion on heterogeneous computing platforms with OpenCL

NASA Astrophysics Data System (ADS)

Fabien-Ouellet, Gabriel; Gloaguen, Erwan; Giroux, Bernard

2017-03-01

Full Waveform Inversion (FWI) aims at recovering the elastic parameters of the Earth by matching recordings of the ground motion with the direct solution of the wave equation. Modeling the wave propagation for realistic scenarios is computationally intensive, which limits the applicability of FWI. The current hardware evolution brings increasing parallel computing power that can speed up the computations in FWI. However, to take advantage of the diversity of parallel architectures presently available, new programming approaches are required. In this work, we explore the use of OpenCL to develop a portable code that can take advantage of the many parallel processor architectures now available. We present a program called SeisCL for 2D and 3D viscoelastic FWI in the time domain. The code computes the forward and adjoint wavefields using finite-difference and outputs the gradient of the misfit function given by the adjoint state method. To demonstrate the code portability on different architectures, the performance of SeisCL is tested on three different devices: Intel CPUs, NVidia GPUs and Intel Xeon PHI. Results show that the use of GPUs with OpenCL can speed up the computations by nearly two orders of magnitudes over a single threaded application on the CPU. Although OpenCL allows code portability, we show that some device-specific optimization is still required to get the best performance out of a specific architecture. Using OpenCL in conjunction with MPI allows the domain decomposition of large models on several devices located on different nodes of a cluster. For large enough models, the speedup of the domain decomposition varies quasi-linearly with the number of devices. Finally, we investigate two different approaches to compute the gradient by the adjoint state method and show the significant advantages of using OpenCL for FWI.

Family satisfaction, pain, and quality-of-life in emerging adults with spina bifida: a longitudinal analysis.

PubMed

Bellin, Melissa H; Dicianno, Brad E; Osteen, Philip; Dosa, Nienke; Aparicio, Elizabeth; Braun, Patricia; Zabel, T Andrew

2013-08-01

This study uses the Life Course Model for Spina Bifida (SB) to advance knowledge of factors associated with change in quality-of-life (QOL) among emerging adults with SB. Forty-eight participants (mean [SD], 22.04 [2.16] yrs) completed self-report questionnaires at two time points, 15 mos apart. Four QOL domains (physical health, psychological, social relationships, and environment) were measured using the World Health Organization QOL-BREF version. SB clinical data were collected via chart reviews. Paired t tests and reliable change indices evaluated group- and individual-level QOL change, respectively. Multiple regression analyses tested the contributions of the Life Course variables in explaining change in QOL over time. No significant group-level differences in the QOL domains were found between time 1 and time 2, but there was substantial individual variation in QOL over time. SB severity was related to a decline only in psychological QOL (B = -0.68, P = 0.02). Increased pain was associated with reduced physical health (B = -0.29, P = 0.049) and psychological (B = -0.29, P = 0.03) QOL at time 2, whereas greater family satisfaction was related to improved QOL in several domains. Clinicians should be aware of the negative impact of pain and the protective influence of family satisfaction on QOL in emerging adults with SB.

Archaea recruited D-Tyr-tRNATyr deacylase for editing in Thr-tRNA synthetase.

PubMed

Rigden, Daniel J

2004-12-01

Aminoacyl-tRNA synthetases (AARSs) are key players in the maintenance of the genetic code through correct pairing of amino acids with their cognate tRNA molecules. To this end, some AARSs, as well as seeking to recognize the correct amino acid during synthesis of aminoacyl-tRNA, enhance specificity through recognition of mischarged aminoacyl-tRNA molecules in a separate editing reaction. Recently, an editing domain, of uncertain provenance, idiosyncratic to some archaeal ThrRSs has been characterized. Here, sequence analyses and molecular modeling are reported that clearly show a relationship of the archaea-specific ThrRS editing domains with d-Tyr-tRNATyr deacylases (DTDs). The model enables the identification of the catalytic site and other substrate binding residues, as well as the proposal of a likely catalytic mechanism. Interestingly, typical DTD sequences, common in bacteria and eukaryotes, are entirely absent in archaea, consistent with an evolutionary scheme in which DTD was co-opted to serve as a ThrRS editing domain in archaea soon after their divergence from eukaryotes. A group of present-day archaebacteria contain a ThrRS obtained from a bacterium by horizontal gene transfer. In some of these cases a vestigial version of the original archaeal ThrRS, of potentially novel function, is maintained.

Archaea recruited d-Tyr-tRNATyr deacylase for editing in Thr–tRNA synthetase

PubMed Central

RIGDEN, DANIEL J.

2004-01-01

Aminoacyl–tRNA synthetases (AARSs) are key players in the maintenance of the genetic code through correct pairing of amino acids with their cognate tRNA molecules. To this end, some AARSs, as well as seeking to recognize the correct amino acid during synthesis of aminoacyl–tRNA, enhance specificity through recognition of mischarged aminoacyl–tRNA molecules in a separate editing reaction. Recently, an editing domain, of uncertain provenance, idiosyncratic to some archaeal ThrRSs has been characterized. Here, sequence analyses and molecular modeling are reported that clearly show a relationship of the archaea-specific ThrRS editing domains with d-Tyr-tRNATyr deacylases (DTDs). The model enables the identification of the catalytic site and other substrate binding residues, as well as the proposal of a likely catalytic mechanism. Interestingly, typical DTD sequences, common in bacteria and eukaryotes, are entirely absent in archaea, consistent with an evolutionary scheme in which DTD was co-opted to serve as a ThrRS editing domain in archaea soon after their divergence from eukaryotes. A group of present-day archaebacteria contain a ThrRS obtained from a bacterium by horizontal gene transfer. In some of these cases a vestigial version of the original archaeal ThrRS, of potentially novel function, is maintained. PMID:15525705

Protection with Recombinant Clostridium botulinum C1 and D Binding Domain Subunit (Hc) Vaccines Against C and D Neurotoxins

DTIC Science & Technology

2007-03-16

A p o p f b a © K 1 c s r h a d t f f r i 0 d Vaccine 25 (2007) 4273–4282 Protection with recombinant Clostridium botulinum C1 and D binding domain...reserved. r-bindin s r t r w i t l s eywords: Botulinum neurotoxin subtypes; Recombinant vaccine; Recepto . Introduction Botulism is the collective term...amedd.army.mil (L.A. Smith). e c t B i T c s 264-410X/$ – see front matter © 2007 Elsevier Ltd. All rights reserved. oi:10.1016/j.vaccine

Real-Time Implementation of a Speech Digitization Algorithm Combining Time-Domain Harmonic Scaling and Adaptive Residual Coding. Volume 1.

DTIC Science & Technology

1983-06-01

recomuended values are b1 - 1.79 b2 - -1.40 b3 - 0.57 b4 - -0.15 s - 0.95 abias - 0.001 g - 0.15 The bi are determined using the technique suggested by...R.A. McDonald (1966). The term, max{.), computes the biased percent change desired. The abias term helps the coefficient move from the zero level

Genetic analysis of LRRK2 functional domains in Brazilian patients with Parkinson's disease.

PubMed

Abdalla-Carvalho, C B; Santos-Rebouças, C B; Guimarães, B C; Campos, M; Pereira, J S; de Rosso, A L Zuma; Nicaretta, D H; Marinho e Silva, M; dos Santos, Mendonça J; Pimentel, M M G

2010-12-01

Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) have been associated with Parkinson's disease (PD), and the majority of the pathogenic variants are located in the ROC and MAPKKK domains. Exons 29-31 and 38-44 (ROC and MAPKKK domains) were sequenced in 204 patients with PD, mostly Brazilian. We identified four polymorphisms, a novel silent variant p.R1398R and four substitutions: p.T1410M, p.G2019S, p.Y2189C and the novel variant p.C2139S. The most prevalent mutation was the p.G2019S (2.4%). We consider that the p.T1410M and the p.Y2189C variants are probably polymorphisms and that the p.C2139S mutation is potentially pathogenic. © 2010 The Author(s). European Journal of Neurology © 2010 EFNS.

Developing a Machine-Supported Coding System for Constructed-Response Items in PISA. Research Report. ETS RR-17-47

ERIC Educational Resources Information Center

Yamamoto, Kentaro; He, Qiwei; Shin, Hyo Jeong; von Davier, Mattias

2017-01-01

Approximately a third of the Programme for International Student Assessment (PISA) items in the core domains (math, reading, and science) are constructed-response items and require human coding (scoring). This process is time-consuming, expensive, and prone to error as often (a) humans code inconsistently, and (b) coding reliability in…

Alternative splicing for members of human mosaic domain superfamilies. I. The CH and LIM domains containing group of proteins.

PubMed

Friedberg, Felix

2009-05-01

In this paper we examine (restricted to homo sapiens) the products resulting from gene duplication and the subsequent alternative splicing for the members of a multidomain group of proteins which possess the evolutionary conserved calponin homology CH domain, i.e. an "actin binding domain", as a singlet and which, in addition, contain the conserved cysteine rich double Zn finger possessing Lim domain, also as a singlet. Seven genes, resulting from gene duplications, were identified that code for seven group members for which pre-mRNAs appear to have undergone multiple alternative splicing: Mical 1, 2 and 3 are located on chromosomes 6q21, 11p15 and 22q11, respectively. The LMO7 gene is present on chromosome 13q22 and the LIMCH1 gene on chromosome 4p13. Micall1 is mapped to chromosome 22q13 and Micall2 to chromosome 7p22. Translated Gen/Bank ESTs suggest the existence of multiple products alternatively spliced from the pre-mRNAs encoded by these genes. Characteristic indicators of such splicing among the proteins derived from one gene must include containment of some common extensive 100% identical regions. In some instances only one exon might be partly or completely eliminated. Sometimes alternative splicing is also associated with an increased frequency of creation of an exon or part of an exon from an intron. Not only coding regions for the body of the protein but also for its N- or -C ends could be affected by the splicing. If created forms are merely beginning at different starting points but remain identical in sequence thereafter, their existence as products of alternate splicing must be questioned. In the splicings, described in this paper, multiple isoforms rather than a single isoform appear as products during the gene expression.

Maternal abuse history, postpartum depression, and parenting: links with preschoolers' internalizing problems.

PubMed

Madigan, Sheri; Wade, Mark; Plamondon, Andre; Jenkins, Jennifer

2015-01-01

The current study examined a temporal cascade linking mothers' history of abuse with their children's internalizing difficulties through proximal processes such as maternal postnatal depressive symptoms and responsive parenting. Participants consisted of 490 mother-child dyads assessed at three time points when children were, on average, 2 months old at Time 1 (T1), 18 months at Time 2 (T2), and 36 months at Time 3 (T3). Maternal abuse history and depressive symptoms were assessed via questionnaires at T1. Observations of responsive parenting were collected at T2 and were coded using a validated coding scheme. Children's internalizing difficulties were assessed in the preschool period using averaged parental reports. Path analysis revealed that maternal physical abuse was associated with depressive symptoms postnatally, which were in turn associated with children's internalizing behavior at 36 months of age. We also found that the association between physical abuse history and responsive parenting operated indirectly through maternal depressive symptoms. These findings remained after controlling for covariates including socioeconomic status, child gender, and age. After accounting for physical abuse history, sexual abuse history was not associated with child internalizing problems either directly or indirectly through maternal depressive symptoms and/or parenting behavior. Thus, mothers' physical abuse history is a risk factor for relatively poor mental health, which is itself predictive of both later parenting behavior and children's internalizing problems. © 2015 Michigan Association for Infant Mental Health.

Model-driven requirements engineering (MDRE) for real-time ultra-wide instantaneous bandwidth signal simulation

NASA Astrophysics Data System (ADS)

Chang, Daniel Y.; Rowe, Neil C.

2013-05-01

While conducting a cutting-edge research in a specific domain, we realize that (1) requirements clarity and correctness are crucial to our success [1], (2) hardware is hard to change, most work is in software requirements development, coding and testing [2], (3) requirements are constantly changing, so that configurability, reusability, scalability, adaptability, modularity and testability are important non-functional attributes [3], (4) cross-domain knowledge is necessary for complex systems [4], and (5) if our research is successful, the results could be applied to other domains with similar problems. In this paper, we propose to use model-driven requirements engineering (MDRE) to model and guide our requirements/development, since models are easy to understand, execute, and modify. The domain for our research is Electronic Warfare (EW) real-time ultra-wide instantaneous bandwidth (IBW1) signal simulation. The proposed four MDRE models are (1) Switch-and-Filter architecture, (2) multiple parallel data bit streams alignment, (3) post-ADC and pre-DAC bits re-mapping, and (4) Discrete Fourier Transform (DFT) filter bank. This research is unique since the instantaneous bandwidth we are dealing with is in gigahertz range instead of conventional megahertz.

A large shRNA library approach identifies lncRNA Ntep as an essential regulator of cell proliferation

PubMed Central

Beermann, Julia; Kirste, Dominique; Iwanov, Katharina; Lu, Dongchao; Kleemiß, Felix; Kumarswamy, Regalla; Schimmel, Katharina; Bär, Christian; Thum, Thomas

2018-01-01

The mammalian cell cycle is a complex and tightly controlled event. Myriads of different control mechanisms are involved in its regulation. Long non-coding RNAs (lncRNA) have emerged as important regulators of many cellular processes including cellular proliferation. However, a more global and unbiased approach to identify lncRNAs with importance for cell proliferation is missing. Here, we present a lentiviral shRNA library-based approach for functional lncRNA profiling. We validated our library approach in NIH3T3 (3T3) fibroblasts by identifying lncRNAs critically involved in cell proliferation. Using stringent selection criteria we identified lncRNA NR_015491.1 out of 3842 different RNA targets represented in our library. We termed this transcript Ntep (non-coding transcript essential for proliferation), as a bona fide lncRNA essential for cell cycle progression. Inhibition of Ntep in 3T3 and primary fibroblasts prevented normal cell growth and expression of key fibroblast markers. Mechanistically, we discovered that Ntep is important to activate P53 concomitant with increased apoptosis and cell cycle blockade in late G2/M. Our findings suggest Ntep to serve as an important regulator of fibroblast proliferation and function. In summary, our study demonstrates the applicability of an innovative shRNA library approach to identify long non-coding RNA functions in a massive parallel approach. PMID:29099486

Control and Optimization of Regenerative Power Flow in 21st Century Airlifters

DTIC Science & Technology

2001-12-01

Figure 3.14. 32 R,=50 Li V , Input Voltage Respose Output Voltage Response’ vaAvB< 40V AVណ t t Figure 3.14. Time domain constraints for the converter...as it will influence the rate of rise of the current pulse. In the current work, L is limited to Self -inductance of the entire assembly is found under

Molecular and cellular characteristics of ABCA3 mutations associated with diffuse parenchymal lung diseases in children

PubMed Central

Flamein, Florence; Riffault, Laure; Muselet-Charlier, Céline; Pernelle, Julie; Feldmann, Delphine; Jonard, Laurence; Durand-Schneider, Anne-Marie; Coulomb, Aurore; Maurice, Michèle; Nogee, Lawrence M.; Inagaki, Nobuya; Amselem, Serge; Dubus, Jean Christophe; Rigourd, Virginie; Brémont, François; Marguet, Christophe; Brouard, Jacques; de Blic, Jacques; Clement, Annick; Epaud, Ralph; Guillot, Loïc

2012-01-01

ABCA3 (ATP-binding cassette subfamily A, member 3) is expressed in the lamellar bodies of alveolar type II cells and is crucial to pulmonary surfactant storage and homeostasis. ABCA3 gene mutations have been associated with neonatal respiratory distress (NRD) and pediatric interstitial lung disease (ILD). The objective of this study was to look for ABCA3 gene mutations in patients with severe NRD and/or ILD. The 30 ABCA3 coding exons were screened in 47 patients with severe NRD and/or ILD. ABCA3 mutations were identified in 10 out of 47 patients, including 2 homozygous, 5 compound heterozygous and 3 heterozygous patients. SP-B and SP-C expression patterns varied across patients. Among patients with ABCA3 mutations, five died shortly after birth and five developed ILD (including one without NRD). Functional studies of p.D253H and p.T1173R mutations revealed that p.D253H and p.T1173R induced abnormal lamellar bodies. Additionally, p.T1173R increased IL-8 secretion in vitro. In conclusion, we identified new ABCA3 mutations in patients with life-threatening NRD and/or ILD. Two mutations associated with ILD acted via different pathophysiological mechanisms despite similar clinical phenotypes. PMID:22068586

Isosurface Display of 3-D Scalar Fields from a Meteorological Model on Google Earth

DTIC Science & Technology

2013-07-01

facets to four, we have chosen to adopt and implement a revised method discussed and made available by Bourke (1994), which can accommodate up to...five facets for a given grid cube. While the published code from Bourke (1994) is in the public domain, it was originally implemented in the C...and atmospheric temperatures. 17 4. References Bourke , P. Polygonising a Scalar Field. http://paulbourke.net/geometry/polygonise

Next generation sequencing yields the complete mitochondrial genome of the Hornlip mullet Plicomugil labiosus (Teleostei: Mugilidae).

PubMed

Shen, Kang-Ning; Chen, Ching-Hung; Hsiao, Chung-Der

2016-05-01

In this study, the complete mitogenome sequence of hornlip mullet Plicomugil labiosus (Teleostei: Mugilidae) has been sequenced by next-generation sequencing method. The assembled mitogenome, consisting of 16,829 bp, had the typical vertebrate mitochondrial gene arrangement, including 13 protein coding genes, 22 transfer RNAs, 2 ribosomal RNAs genes and a non-coding control region of D-loop. D-loop contains 1057 bp length is located between tRNA-Pro and tRNA-Phe. The overall base composition of P. labiosus is 28.0% for A, 29.3% for C, 15.5% for G and 27.2% for T. The complete mitogenome may provide essential and important DNA molecular data for further population, phylogenetic and evolutionary analysis for Mugilidae.

Candida ficus sp. nov., a novel yeast species from the gut of Apriona germari larvae.

PubMed

Hui, Feng-Li; Niu, Qiu-Hong; Ke, Tao; Liu, Zheng

2012-11-01

A novel yeast species is described based on three strains from the gut of wood-boring larvae collected in a tree trunk of Ficus carica cultivated in parks near Nanyang, central China. Phylogenetic analysis based on sequences of the D1/D2 domains of the large subunit rRNA gene showed that these strains occurred in a separate clade that was genetically distinct from all known ascomycetous yeasts. In terms of pairwise sequence divergence, the novel strains differed by 15.3% divergence from the type strain of Pichia terricola, and by 15.8% divergence from the type strains of Pichia exigua and Candida rugopelliculosa in the D1/D2 domains. All three are ascomycetous yeasts in the Pichia clade. Unlike P. terricola, P. exigua and C. rugopelliculosa, the novel isolates did not ferment glucose. The name Candida ficus sp. nov. is proposed to accommodate these highly divergent organisms, with STN-8(T) (=CICC 1980(T)=CBS 12638(T)) as the type strain.

Pooled Sequencing of 531 Genes in Inflammatory Bowel Disease Identifies an Associated Rare Variant in BTNL2 and Implicates Other Immune Related Genes

PubMed Central

Prescott, Natalie J.; Lehne, Benjamin; Stone, Kristina; Lee, James C.; Taylor, Kirstin; Knight, Jo; Papouli, Efterpi; Mirza, Muddassar M.; Simpson, Michael A.; Spain, Sarah L.; Lu, Grace; Fraternali, Franca; Bumpstead, Suzannah J.; Gray, Emma; Amar, Ariella; Bye, Hannah; Green, Peter; Chung-Faye, Guy; Hayee, Bu’Hussain; Pollok, Richard; Satsangi, Jack; Parkes, Miles; Barrett, Jeffrey C.; Mansfield, John C.; Sanderson, Jeremy; Lewis, Cathryn M.; Weale, Michael E.; Schlitt, Thomas; Mathew, Christopher G.

2015-01-01

The contribution of rare coding sequence variants to genetic susceptibility in complex disorders is an important but unresolved question. Most studies thus far have investigated a limited number of genes from regions which contain common disease associated variants. Here we investigate this in inflammatory bowel disease by sequencing the exons and proximal promoters of 531 genes selected from both genome-wide association studies and pathway analysis in pooled DNA panels from 474 cases of Crohn’s disease and 480 controls. 80 variants with evidence of association in the sequencing experiment or with potential functional significance were selected for follow up genotyping in 6,507 IBD cases and 3,064 population controls. The top 5 disease associated variants were genotyped in an extension panel of 3,662 IBD cases and 3,639 controls, and tested for association in a combined analysis of 10,147 IBD cases and 7,008 controls. A rare coding variant p.G454C in the BTNL2 gene within the major histocompatibility complex was significantly associated with increased risk for IBD (p = 9.65x10−10, OR = 2.3[95% CI = 1.75–3.04]), but was independent of the known common associated CD and UC variants at this locus. Rare (<1%) and low frequency (1–5%) variants in 3 additional genes showed suggestive association (p<0.005) with either an increased risk (ARIH2 c.338-6C>T) or decreased risk (IL12B p.V298F, and NICN p.H191R) of IBD. These results provide additional insights into the involvement of the inhibition of T cell activation in the development of both sub-phenotypes of inflammatory bowel disease. We suggest that although rare coding variants may make a modest overall contribution to complex disease susceptibility, they can inform our understanding of the molecular pathways that contribute to pathogenesis. PMID:25671699

Review of particle-in-cell modeling for the extraction region of large negative hydrogen ion sources for fusion

NASA Astrophysics Data System (ADS)

Wünderlich, D.; Mochalskyy, S.; Montellano, I. M.; Revel, A.

2018-05-01

Particle-in-cell (PIC) codes are used since the early 1960s for calculating self-consistently the motion of charged particles in plasmas, taking into account external electric and magnetic fields as well as the fields created by the particles itself. Due to the used very small time steps (in the order of the inverse plasma frequency) and mesh size, the computational requirements can be very high and they drastically increase with increasing plasma density and size of the calculation domain. Thus, usually small computational domains and/or reduced dimensionality are used. In the last years, the available central processing unit (CPU) power strongly increased. Together with a massive parallelization of the codes, it is now possible to describe in 3D the extraction of charged particles from a plasma, using calculation domains with an edge length of several centimeters, consisting of one extraction aperture, the plasma in direct vicinity of the aperture, and a part of the extraction system. Large negative hydrogen or deuterium ion sources are essential parts of the neutral beam injection (NBI) system in future fusion devices like the international fusion experiment ITER and the demonstration reactor (DEMO). For ITER NBI RF driven sources with a source area of 0.9 × 1.9 m2 and 1280 extraction apertures will be used. The extraction of negative ions is accompanied by the co-extraction of electrons which are deflected onto an electron dump. Typically, the maximum negative extracted ion current is limited by the amount and the temporal instability of the co-extracted electrons, especially for operation in deuterium. Different PIC codes are available for the extraction region of large driven negative ion sources for fusion. Additionally, some effort is ongoing in developing codes that describe in a simplified manner (coarser mesh or reduced dimensionality) the plasma of the whole ion source. The presentation first gives a brief overview of the current status of the ion source development for ITER NBI and of the PIC method. Different PIC codes for the extraction region are introduced as well as the coupling to codes describing the whole source (PIC codes or fluid codes). Presented and discussed are different physical and numerical aspects of applying PIC codes to negative hydrogen ion sources for fusion as well as selected code results. The main focus of future calculations will be the meniscus formation and identifying measures for reducing the co-extracted electrons, in particular for deuterium operation. The recent results of the 3D PIC code ONIX (calculation domain: one extraction aperture and its vicinity) for the ITER prototype source (1/8 size of the ITER NBI source) are presented.

Physiological falls risk assessment in older people with Alzheimer's disease.

PubMed

Lorbach, Edwina R; Webster, Kate E; Menz, Hylton B; Wittwer, Joanne E; Merory, John R

2007-01-01

Falls are common in people with Alzheimer's disease (AD). There is some evidence that deficits in vision, peripheral sensation, strength, reaction time and balance may be partly responsible for this increased risk. To determine the feasibility and test-retest reliability of a physiological test battery designed to assess falls risk [the Physiological Profile Assessment (PPA)] in people with AD, and to compare their PPA scores to age- and sex-matched controls. Twenty-one community-dwelling people with probable, mild to moderate AD aged 63-91 years, and 21 age- and sex-matched controls underwent the PPA tests and the Mini-Mental State Examination. All tests were then repeated in the AD group to determine test-retest reliability. Most of the PPA tests could be successfully administered to participants with AD. The AD group had a significantly higher overall falls risk score (t(40) = -2.41, p < 0.02), slower hand (t(40) = -4.86, p < 0.01) and foot reaction time (t(40) = -2.26, p < 0.05) and worse coordinated stability (t(40) = -2.40, p < 0.05) than the controls. Physiological falls risk assessment is feasible in older people with mild to moderate AD. Older people with AD demonstrate significant impairments in several physiological domains, particularly reaction time, compared to controls.

Fission time scale from pre-scission neutron and α multiplicities in the 16O + 194Pt reaction

NASA Astrophysics Data System (ADS)

Kapoor, K.; Verma, S.; Sharma, P.; Mahajan, R.; Kaur, N.; Kaur, G.; Behera, B. R.; Singh, K. P.; Kumar, A.; Singh, H.; Dubey, R.; Saneesh, N.; Jhingan, A.; Sugathan, P.; Mohanto, G.; Nayak, B. K.; Saxena, A.; Sharma, H. P.; Chamoli, S. K.; Mukul, I.; Singh, V.

2017-11-01

Pre- and post-scission α -particle multiplicities have been measured for the reaction 16O+P194t at 98.4 MeV forming R210n compound nucleus. α particles were measured at various angles in coincidence with the fission fragments. Moving source technique was used to extract the pre- and post-scission contributions to the particle multiplicity. Study of the fission mechanism using the different probes are helpful in understanding the detailed reaction dynamics. The neutron multiplicities for this reaction have been reported earlier. The multiplicities of neutrons and α particles were reproduced using standard statistical model code joanne2 by varying the transient (τt r) and saddle to scission (τs s c) times. This code includes deformation dependent-particle transmission coefficients, binding energies and level densities. Fission time scales of the order of 50-65 ×10-21 s are required to reproduce the neutron and α -particle multiplicities.

Intranasal P particle vaccine provided partial cross-variant protection against human GII.4 norovirus diarrhea in gnotobiotic pigs.

PubMed

Kocher, Jacob; Bui, Tammy; Giri-Rachman, Ernawati; Wen, Ke; Li, Guohua; Yang, Xingdong; Liu, Fangning; Tan, Ming; Xia, Ming; Zhong, Weiming; Jiang, Xi; Yuan, Lijuan

2014-09-01

Noroviruses (NoVs) are the leading cause of nonbacterial acute gastroenteritis worldwide in people of all ages. The P particle is a novel vaccine candidate derived from the protruding (P) domain of the NoV VP1 capsid protein. This study utilized the neonatal gnotobiotic pig model to evaluate the protective efficacies of primary infection, P particles, and virus-like particles (VLPs) against NoV infection and disease and the T cell responses to these treatments. Pigs either were vaccinated intranasally with GII.4/1997 NoV (VA387)-derived P particles or VLPs or were inoculated orally with a GII.4/2006b NoV variant. At postinoculation day (PID) 28, pigs either were euthanized or were challenged with the GII.4/2006b variant and monitored for diarrhea and virus shedding for 7 days. The T cell responses in intestinal and systemic lymphoid tissues were examined. Primary NoV infection provided 83% homologous protection against diarrhea and 49% homologous protection against virus shedding, while the P particle and VLP vaccines provided cross-variant protection (47% and 60%, respectively) against diarrhea. The protection rates against diarrhea are significantly inversely correlated with T cell expansion in the duodenum and are positively correlated with T cell expansion in the ileum and spleen. The P particle vaccine primed for stronger immune responses than VLPs, including significantly higher numbers of activated CD4+ T cells in all tissues, gamma interferon-producing (IFN-γ+) CD8+ T cells in the duodenum, regulatory T cells (Tregs) in the blood, and transforming growth factor β (TGF-β)-producing CD4+ CD25- FoxP3+ Tregs in the spleen postchallenge, indicating that P particles are more immunogenic than VLPs at the same dose. In conclusion, the P particle vaccine is a promising vaccine candidate worthy of further development. The norovirus (NoV) P particle is a vaccine candidate derived from the protruding (P) domain of the NoV VP1 capsid protein. P particles can be easily produced in Escherichia coli at high yields and thus may be more economically viable than the virus-like particle (VLP) vaccine. This study demonstrated, for the first time, the cross-variant protection (46.7%) of the intranasal P particle vaccine against human NoV diarrhea and revealed in detail the intestinal and systemic T cell responses by using the gnotobiotic pig model. The cross-variant protective efficacy of the P particle vaccine was comparable to that of the VLP vaccine in pigs (60%) and to the homologous protective efficacy of the VLP vaccine in humans (47%). NoV is now the leading cause of pediatric dehydrating diarrhea, responsible for approximately 1 million hospital visits for U.S. children and 218,000 deaths in developing countries. The P particle vaccine holds promise for reducing the disease burden and mortality. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Issues in Developing a Surveillance Case Definition for Nonfatal Suicide Attempt and Intentional Self-harm Using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) Coded Data.

PubMed

Hedegaard, Holly; Schoenbaum, Michael; Claassen, Cynthia; Crosby, Alex; Holland, Kristin; Proescholdbell, Scott

2018-02-01

Suicide and intentional self-harm are among the leading causes of death in the United States. To study this public health issue, epidemiologists and researchers often analyze data coded using the International Classification of Diseases (ICD). Prior to October 1, 2015, health care organizations and providers used the clinical modification of the Ninth Revision of ICD (ICD-9-CM) to report medical information in electronic claims data. The transition in October 2015 to use of the clinical modification of the Tenth Revision of ICD (ICD-10-CM) resulted in the need to update methods and selection criteria previously developed for ICD-9-CM coded data. This report provides guidance on the use of ICD-10-CM codes to identify cases of nonfatal suicide attempts and intentional self-harm in ICD-10-CM coded data sets. ICD-10-CM codes for nonfatal suicide attempts and intentional self-harm include: X71-X83, intentional self-harm due to drowning and submersion, firearms, explosive or thermal material, sharp or blunt objects, jumping from a high place, jumping or lying in front of a moving object, crashing of motor vehicle, and other specified means; T36-T50 with a 6th character of 2 (except for T36.9, T37.9, T39.9, T41.4, T42.7, T43.9, T45.9, T47.9, and T49.9, which are included if the 5th character is 2), intentional self-harm due to drug poisoning (overdose); T51-T65 with a 6th character of 2 (except for T51.9, T52.9, T53.9, T54.9, T56.9, T57.9, T58.0, T58.1, T58.9, T59.9, T60.9, T61.0, T61.1, T61.9, T62.9, T63.9, T64.0, T64.8, and T65.9, which are included if the 5th character is 2), intentional self-harm due to toxic effects of nonmedicinal substances; T71 with a 6th character of 2, intentional self-harm due to asphyxiation, suffocation, strangulation; and T14.91, Suicide attempt. Issues to consider when selecting records for nonfatal suicide attempts and intentional self-harm from ICD-10-CM coded administrative data sets are also discussed. All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as to source, however, is appreciated.

Seismic anisotropy of the upper mantle beneath Fennoscandia - Preliminary results of anisotropic tomography with novel code AniTomo

NASA Astrophysics Data System (ADS)

Munzarova, Helena; Plomerova, Jaroslava; Kissling, Edi; Vecsey, Ludek; Babuska, Vladislav

2016-04-01

Seismological investigations of the continental mantle lithosphere, particularly its anisotropic structure, advance our understanding of plate tectonics and formation of continents. Orientation of the anisotropic fabrics reflect stress field during the lithosphere origin and its later deformations. We process teleseismic body waves recorded during passive seismic experiments SVEKALAPKO (1998-1999) and LAPNET (2007-2009), deployed in the south-central and northern Fennoscandia, around the contact of the Archean and Proterozoic parts of the shield, to retrieve both anisotropic and isotropic velocity images of the upper mantle. Standard isotropic teleseismic P-wave tomography distinguishes two major regions of the mantle lithosphere in the northern part of Fennoscandia, boundary of which follows the surface trace of the Baltic-Bothnia Megashear Zone (BBZ). Apart from that, joint interpretation of lateral variations of anisotropic P- and SKS-wave pattern detected domains of mantle lithosphere with differently oriented anisotropic fabrics within those two regions (Vecsey et al., Tectonophysics, 2007; Plomerova et al., Solid Earth, 2011). The retrieved anisotropy reflects fossil fabrics of the mantle lithosphere (Babuska and Plomerova, Phys. Earth Planet. Int., 2006). The contact of the Proterozoic and Archean Fennoscandia appears as a broad transition in the south-central Fennoscandia (Vecsey et al., Tectonophysics, 2007), while the contact seems to be more distinct towards the north. We have developed a novel code (AniTomo) that allows us to invert relative P-wave travel time residuals for coupled isotropic-anisotropic P-wave velocity models assuming weak hexagonal anisotropy with symmetry axis oriented generally in 3D. The code was successfully tested on synthetic data and here we present results of its first application to real data. The region of Fennoscandia seems to be a right choice for the first calculation of anisotropic tomography with the new code as this Precambrian region is tectonicly stable and it has thick anisotropic mantle lithosphere (Plomerova and Babuska, Lithos, 2010) without significant thermal heterogeneities.

Flexible DNA binding of the BTB/POZ-domain protein FBI-1.

PubMed

Pessler, Frank; Hernandez, Nouria

2003-08-01

POZ-domain transcription factors are characterized by the presence of a protein-protein interaction domain called the POZ or BTB domain at their N terminus and zinc fingers at their C terminus. Despite the large number of POZ-domain transcription factors that have been identified to date and the significant insights that have been gained into their cellular functions, relatively little is known about their DNA binding properties. FBI-1 is a BTB/POZ-domain protein that has been shown to modulate HIV-1 Tat trans-activation and to repress transcription of some cellular genes. We have used various viral and cellular FBI-1 binding sites to characterize the interaction of a POZ-domain protein with DNA in detail. We find that FBI-1 binds to inverted sequence repeats downstream of the HIV-1 transcription start site. Remarkably, it binds efficiently to probes carrying these repeats in various orientations and spacings with no particular rotational alignment, indicating that its interaction with DNA is highly flexible. Indeed, FBI-1 binding sites in the adenovirus 2 major late promoter, the c-fos gene, and the c-myc P1 and P2 promoters reveal variously spaced direct, inverted, and everted sequence repeats with the consensus sequence G(A/G)GGG(T/C)(C/T)(T/C)(C/T) for each repeat.

Personnel-General: Army Substance Abuse Program Civilian Services

DTIC Science & Technology

2001-10-15

destroyed. Additional reproduction and distribution of completed records is prohibited. c. SECTION I. IDENTIFICATION. (1) Block I. Date of Report. Enter...AMPHETAMINE B BARBITUATES C COCAINE H HALLUCINOGENS (LSD) M METHAQUALONE, SEDATIVE, HYPNOTIC , OR ANXIOLYTIC O OPIATES P PHENCYCLIDINE (PCP) T CANNABIS...Table 5–6 Codes for TABLE F (T-DIAG-CODE) Code Rejection Reason 30390 ALCOHOL DEPENDENCE 30400 OPIOID DEPENDENCE 30410 SEDATIVE, HYPNOTIC , OR ANXIOLYTIC

Candida northwykensis sp. nov., a novel yeast isolated from the gut of the click beetle Melanotus villosus.

PubMed

Ravella, Sreenivas Rao; Donovan, Neil; James, Stephen A; Shivaji, Sisinthy; Arunasri, Kotakonda; Bond, Christopher J; Roberts, Ian N; Hobbs, Phil J

2011-08-01

Two yeast morphotypes, BET 4(T) and BET 7, were isolated from the gut of click beetle Melanotus villosus. Click beetles were collected from the decaying timber within the woodlands of North Wyke Research, South West England, UK (latitude, 50°46'29″N; longitude, 3°55'23″W). Morphotype BET 7 was identified as Debaryomyces hansenii, and the other morphotype, BET 4(T), was found to differ from Priceomyces castillae and Priceomyces haplophilus, its closest phylogenetic neighbours, by 5.0% with respect to the nucleotide sequence of the D1/D2 domain of the large-subunit (LSU) rRNA gene, and by 8.0% with respect to the ribosomal internal-transcribed spacer (ITS) region. BET 4(T) also differ from P. castillae and P. haplophilus in a number of different phenotypic characteristics. Thus, based on the unique nucleotide sequences of its D1/D2 domain and ITS region, its physiological characteristics and an inability to sporulate, strain BET 4(T) is assigned the status of a new species of Candida, for which the name Candida northwykensis sp. nov., is proposed. The type strain is BET 4(T) (NCYC 3525(T) = CBS 11370(T)).

Interactions of polyomavirus middle T with the SH2 domains of the pp85 subunit of phosphatidylinositol-3-kinase.

PubMed Central

Yoakim, M; Hou, W; Liu, Y; Carpenter, C L; Kapeller, R; Schaffhausen, B S

1992-01-01

The binding of phosphatidylinositol-3-kinase to the polyomavirus middle T antigen is facilitated by tyrosine phosphorylation of middle T on residue 315. The pp85 subunit of phosphatidylinositol-3-kinase contains two SH2 domains, one in the middle of the molecule and one at the C terminus. When assayed by blotting with phosphorylated middle T, the more N-terminal SH2 domain is responsible for binding to middle T. When assayed in solution with glutathione S transferase fusions, both SH2s are capable of binding phosphorylated middle T. While both SH2 fusions can compete with intact pp85 for binding to middle T, the C-terminal SH2 is the more efficient of the two. Interaction between pp85 or its SH2 domains and middle T can be blocked by a synthetic peptide comprising the tyrosine phosphorylation sequence around middle T residue 315. Despite the fact that middle T can interact with both SH2s, these domains are not equivalent. Only the C-terminal SH2-middle T interaction was blocked by anti-SH2 antibody; the two SH2 fusions also interact with different cellular proteins. Images PMID:1380095

An Exposed KID-Like Domain in Human T-Cell Lymphotropic Virus Type 1 Tax Is Responsible for the Recruitment of Coactivators CBP/p300

PubMed Central

Harrod, Robert; Tang, Yong; Nicot, Christophe; Lu, Hsieng S.; Vassilev, Alex; Nakatani, Yoshihiro; Giam, Chou-Zen

1998-01-01

Human T-cell lymphotropic virus type 1 (HTLV-1) transcriptional activation is mediated by the viral transactivator, Tax, and three 21-bp repeats (Tax response element [TxRE]) located in the U3 region of the viral long terminal repeat (LTR). Each TxRE contains a core cyclic AMP response element (CRE) flanked by 5′ G-rich and 3′ C-rich sequences. The TxRE binds CREB (CRE-binding protein) and Tax to form a ternary complex and confers Tax-dependent transactivation. Recent data indicate that Tax functions as a specific link to connect CREB-binding protein (CBP)/p300 in a phosphorylation-independent manner to CREB/ATF-1 assembled on the viral 21-bp repeats. Glutathione S-transferase pull-down performed with Tax deletion mutants and peptide competition have localized the site in Tax critical for binding CBP/p300 to a highly protease-sensitive region around amino acid residues 81 to 95 (81QRTSKTLKVLTPPIT95) which lies between the domains previously proposed to be important for CREB binding and Tax subunit dimerization. Amino acid residues around the trypsin- and chymotrypsin-sensitive sites (88KVL90) of Tax bear resemblance to those in the kinase-inducible domain of CREB (129SRRPSYRKILNE140) surrounding Ser-133, which undergoes signal-induced phosphorylation to recruit CBP/p300. Site-directed mutagenesis of residues in this domain (R82A, K85A, K88A, and V89A) resulted in proteins which failed to transactivate from the HTLV-1 LTR in vivo. These mutants (K85A, K88A, and V89A) bind CREB with similar affinities as wild-type Tax, yet interaction with CBP/p300 is abrogated in various biochemical assays, indicating that the recruitment of CBP/p300 is crucial for Tax transactivation. A Tax mutant, M47, defective in the COOH-terminal transactivation domain, continued to interact with CBP/p300, suggesting that interactions with additional cellular factors are required for proper Tax function. PMID:9710589

Novel mutations of the SRD5A2 and AR genes in Thai patients with 46, XY disorders of sex development.

PubMed

Ittiwut, Chupong; Pratuangdejkul, Jaturong; Supornsilchai, Vichit; Muensri, Sasipa; Hiranras, Yodporn; Sahakitrungruang, Taninee; Watcharasindhu, Suttipong; Suphapeetiporn, Kanya; Shotelersuk, Vorasuk

2017-01-01

Abnormalities of dihydrotestosterone conversion [5α-reductase deficiency: online Mendelian inheritance in man (OMIM) 607306] or actions of androgens [partial androgen insensitivity syndrome (PAIS): OMIM 312300] during the 8th-12th weeks of gestation cause varying degrees of undervirilized external genitalia in 46, XY disorders of sex development (DSD) with increased testosterone production. The objective of the study was to determine clinical and genetic characteristics of Thai patients with 46, XY DSD. A cross-sectional study was conducted in 46, XY DSD with increased testosterone production (n=43) evaluated by a human chorionic gonadotropin (hCG) stimulation test or clinical features consistent with 5α-reductase deficiency or PAIS. PCR sequencing of the entire coding regions of the SRD5A2 and AR genes was performed. Molecular modeling analysis of the androgen receptor-ligand-binding domain (AR-LBD) of a novel mutation was constructed. Mutations were found in seven patients (16.3%): five (11.6%) and two (4.7%) patients had mutations in SRD5A2 and AR, respectively. Two novel mutations, SRD5A2 c.383A>G (p.Y128C) and AR c.2176C>T (p.R726C), were identified. Dimensional structural analysis of the novel mutated AR (p.R726C) revealed that it affected the co-activator binding [binding function-3 (BF-3)], not the testosterone binding site. Short phallus length was associated with 5α-reductase deficiency. Around 16.3% of our patients with 46, XY DSD had 5α-reductase deficiency or PAIS. Two novel mutations of SRD5A2 and AR were identified. The novel mutated AR (p.R726C) might affect the co-activator binding (BF-3), not the testosterone binding site.

Variant in the RFWD3 gene associated with PATN1, a modifier of leopard complex spotting.

PubMed

Holl, H M; Brooks, S A; Archer, S; Brown, K; Malvick, J; Penedo, M C T; Bellone, R R

2016-02-01

Leopard complex spotting (LP), the result of an incompletely dominant mutation in TRPM1, produces a collection of unique depigmentation patterns in the horse. Although the LP mutation allows for expression of the various patterns, other loci are responsible for modification of the extent of white. Pedigree analysis of families segregating for high levels of patterning indicated a single dominant gene, named Pattern-1 (PATN1), as a major modifier of LP. Linkage analysis in two half-sibling families segregating for PATN1 identified a 15-Mb region on ECA3p that warranted further investigation. Whole transcriptome sequencing of skin samples from horses with and without the PATN1 allele was performed to identify genic SNPs for fine mapping. Two Sequenom assays were utilized to genotype 192 individuals from five LP-carrying breeds. The initial panel highlighted a 1.6-Mb region without a clear candidate gene. In the second round of fine mapping, SNP ECA3:23 658 447T>G in the 3'-UTR of RING finger and WD repeat domain 3 (RFWD3) reached a significance level of P = 1.063 × 10(-39). Sequencing of RFWD3 did not identify any coding polymorphisms specific to PATN1 horses. Genotyping of the RFWD3 3'-UTR SNP in 54 additional LP animals and 327 horses from nine breeds not segregating for LP further supported the association (P = 4.17 × 10(-115)). This variant is a strong candidate for PATN1 and may be particularly useful for LP breeders to select for high levels of white patterning. © 2015 Stichting International Foundation for Animal Genetics.

LRP4 third β-propeller domain mutations cause novel congenital myasthenia by compromising agrin-mediated MuSK signaling in a position-specific manner

PubMed Central

Ohkawara, Bisei; Cabrera-Serrano, Macarena; Nakata, Tomohiko; Milone, Margherita; Asai, Nobuyuki; Ito, Kenyu; Ito, Mikako; Masuda, Akio; Ito, Yasutomo; Engel, Andrew G.; Ohno, Kinji

2014-01-01

Congenital myasthenic syndromes (CMS) are heterogeneous disorders in which the safety margin of neuromuscular transmission is compromised by one or more specific mechanisms. Using Sanger and exome sequencing in a CMS patient, we identified two heteroallelic mutations, p.Glu1233Lys and p.Arg1277His, in LRP4 coding for the postsynaptic low-density lipoprotein receptor-related protein 4. LRP4, expressed on the surface of the postsynaptic membrane of the neuromuscular junction, is a receptor for neurally secreted agrin, and LRP4 bound by agrin activates MuSK. Activated MuSK in concert with Dok-7 stimulates rapsyn to concentrate and anchor AChR on the postsynaptic membrane and interacts with other proteins implicated in the assembly and maintenance of the neuromuscular junction. LRP4 also functions as an inhibitor of Wnt/beta-catenin signaling. The identified mutations in LRP4 are located at the edge of its 3rd beta-propeller domain and decrease binding affinity of LRP4 for both MuSK and agrin. Mutations in the LRP4 3rd beta-propeller domain were previously reported to impair Wnt signaling and cause bone diseases including Cenani–Lenz syndactyly syndrome and sclerosteosis-2. By analyzing naturally occurring and artificially introduced mutations in the LRP4 3rd beta-propeller domain, we show that the edge of the domain regulates the MuSK signaling whereas its central cavity governs Wnt signaling. We conclude that LRP4 is a new CMS disease gene and that the 3rd beta propeller domain of LRP4 mediates the two signaling pathways in a position-specific manner. PMID:24234652

Molecular cloning, expression profile, polymorphism and the genetic effects of the dopamine D1 receptor gene on duck reproductive traits.

PubMed

Wang, Cui; Li, Shijun; Li, Chuang; Feng, Yanping; Peng, Xiuli; Gong, Yanzhang

2012-09-01

The dopamine D1 receptor (DRD1), a member of the dopamine receptor (DR) gene family, participates in the regulation of reproductive behaviors in birds. In this study, a 1,390 bp fragment covering the complete coding region (CDS) of duck DRD1 gene was obtained. The cDNA (GenBank: JQ346726) contains a 1,353 bp CDS and a 37 bp 3'- UTR including a TGA termination codon (nucleotides 1,354-1,356 bp). The duck DRD1 shares about 76-96 % nucleic acid identity and 82-98 % amino acid identity with their counterparts in other species. A phylogenetic tree based on amino acid sequences displays that duck DRD1 protein is closely related with those of chicken and zebra finch. The quantitative real-time PCR analysis indicates that the DRD1 mRNA is widely expressed in all examined tissues. Five single nucleotide polymorphisms (SNPs) (c.189A > T, c.507C > T, c.681C > T, c.765A > T, c.1044A > G) in the CDS of duck DRD1 gene were indentified, c.681C > T and c.765A > T were genotyped and analyzed in a two generations duck population by using of PCR-RFLP. Association analysis demonstrated that the c.681C > T genotypes were significantly associated with body weight at sexual maturity (when laying their first egg) (P < 0.01), egg production within 360 days (P < 0.05) and 420 days (P < 0.01); the c.765A > T genotypes were significantly associated with egg shape index and egg shell strength (P < 0.05). Those results suggest that the DRD1 gene may be a potential genetic marker to improve some reproductive traits in ducks.

Activation-induced proteolysis of cytoplasmic domain of zeta in T cell receptors and Fc receptors.

PubMed

Taupin, J L; Anderson, P

1994-12-01

The CD3-T cell receptor (TCR) complex on T cells and the Fc gamma receptor type III (Fc gamma RIII)-zeta-gamma complex on natural killer cells are functionally analogous activation receptors that associate with a family of disulfide-linked dimers composed of the related subunits zeta and gamma. Immunochemical analysis of receptor complexes separated on two-dimensional diagonal gels allowed the identification of a previously uncharacterized zeta-p14 heterodimer. zeta-p14 is a component of both CD3-TCR and Fc gamma RIII-zeta-gamma. Peptide mapping analysis shows that p14 is structurally related to zeta, suggesting that it is either: (i) derived from zeta proteolytically or (ii) the product of an alternatively spliced mRNA. The observation that COS cells transformed with a cDNA encoding zeta express zeta-p14 supports the former possibility. The expression of CD3-TCR complexes including zeta-p14 increases following activation with phorbol 12-myristate 13-acetate or concanavalin A, suggesting that proteolysis of zeta may contribute to receptor modulation or desensitization.

The PH Domain of PDK1 Exhibits a Novel, Phospho-Regulated Monomer-Dimer Equilibrium With Important Implications for Kinase Domain Activation: Single Molecule and Ensemble Studies†

PubMed Central

Ziemba, Brian P.; Pilling, Carissa; Calleja, Véronique; Larijani, Banafshé; Falke, Joseph J.

2013-01-01

Phosphoinositide-Dependent Kinase-1 (PDK1) is an essential master kinase recruited to the plasma membrane by the binding of its C-terminal PH domain to the signaling lipid phosphatidylinositol-3,4-5-trisphosphate (PIP3). Membrane binding leads to PDK1 phospho-activation, but despite the central role of PDK1 in signaling and cancer biology this activation mechanism remains poorly understood. PDK1 has been shown to exist as a dimer in cells, and one crystal structure of its isolated PH domain exhibits a putative dimer interface. It has been proposed that phosphorylation of PH domain residue T513 (or the phospho-mimetic T513E mutation) may regulate a novel PH domain dimer-monomer equilibrium, thereby converting an inactive PDK1 dimer to an active monomer. However, the oligomeric state(s) of the PH domain on the membrane have not yet been determined, nor whether a negative charge at position 513 is sufficient to regulate its oligomeric state. The present study investigates the binding of purified WT and T513E PDK1 PH domains to lipid bilayers containing the PIP3 target lipid, using both single molecule and ensemble measurements. Single molecule analysis of the brightness of fluorescent PH domain shows that the PIP3-bound WT PH domain on membranes is predominantly dimeric, while the PIP3-bound T513E PH domain is monomeric, demonstrating that negative charge at the T513 position is sufficient to dissociate the PH domain dimer and is thus likely to play a central role in PDK1 monomerization and activation. Single molecule analysis of 2-D diffusion of PH domain-PIP3 complexes reveals that the dimeric WT PH domain diffuses at the same rate a single lipid molecule, indicating that only one of its two PIP3 binding sites is occupied and there is little protein penetration into the bilayer as observed for other PH domains. The 2-D diffusion of T513E PH domain is slower, suggesting the negative charge disrupts local structure in a way that enables greater protein insertion into the viscous bilayer, thereby increasing the diffusional friction. Ensemble measurements of PH domain affinity for PIP3 on plasma membrane-like bilayers reveals that dimeric WT PH domain possesses a one-order of magnitude higher target membrane affinity than the previously characterized monomeric PH domains, consistent with a dimerization-triggered, allosterically-enhanced affinity for one PIP3 molecule (a much larger affinity enhancement would be expected for dimerization-triggered binding to two PIP3 molecules). The monomeric T513E PDK1 PH domain, like other monomeric PH domains, exhibits a PIP3 affinity and bound state lifetime that are each a full order of magnitude lower than dimeric WT PH domain, which is predicted to facilitate release of activated, monomeric PDK1 to cytoplasm. Overall, the study yields the first molecular picture of PH domain regulation via electrostatic control of dimer-monomer conversion. PMID:23745598

The PH domain of phosphoinositide-dependent kinase-1 exhibits a novel, phospho-regulated monomer-dimer equilibrium with important implications for kinase domain activation: single-molecule and ensemble studies.

PubMed

Ziemba, Brian P; Pilling, Carissa; Calleja, Véronique; Larijani, Banafshé; Falke, Joseph J

2013-07-16

Phosphoinositide-dependent kinase-1 (PDK1) is an essential master kinase recruited to the plasma membrane by the binding of its C-terminal PH domain to the signaling lipid phosphatidylinositol-3,4,5-trisphosphate (PIP3). Membrane binding leads to PDK1 phospho-activation, but despite the central role of PDK1 in signaling and cancer biology, this activation mechanism remains poorly understood. PDK1 has been shown to exist as a dimer in cells, and one crystal structure of its isolated PH domain exhibits a putative dimer interface. It has been proposed that phosphorylation of PH domain residue T513 (or the phospho-mimetic T513E mutation) may regulate a novel PH domain dimer-monomer equilibrium, thereby converting an inactive PDK1 dimer to an active monomer. However, the oligomeric states of the PH domain on the membrane have not yet been determined, nor whether a negative charge at position 513 is sufficient to regulate its oligomeric state. This study investigates the binding of purified wild-type (WT) and T513E PDK1 PH domains to lipid bilayers containing the PIP3 target lipid, using both single-molecule and ensemble measurements. Single-molecule analysis of the brightness of the fluorescent PH domain shows that the PIP3-bound WT PH domain on membranes is predominantly dimeric while the PIP3-bound T513E PH domain is monomeric, demonstrating that negative charge at the T513 position is sufficient to dissociate the PH domain dimer and is thus likely to play a central role in PDK1 monomerization and activation. Single-molecule analysis of two-dimensional (2D) diffusion of PH domain-PIP3 complexes reveals that the dimeric WT PH domain diffuses at the same rate as a single lipid molecule, indicating that only one of its two PIP3 binding sites is occupied and there is little penetration of the protein into the bilayer as observed for other PH domains. The 2D diffusion of T513E PH domain is slower, suggesting the negative charge disrupts local structure in a way that allows deeper insertion of the protein into the viscous bilayer, thereby increasing the diffusional friction. Ensemble measurements of PH domain affinity for PIP3 on plasma membrane-like bilayers reveal that the dimeric WT PH domain possesses a one order of magnitude higher target membrane affinity than the previously characterized monomeric PH domains, consistent with a dimerization-triggered, allosterically enhanced affinity for one PIP3 molecule (a much larger affinity enhancement would be expected for dimerization-triggered binding to two PIP3 molecules). The monomeric T513E PDK1 PH domain, like other monomeric PH domains, exhibits a PIP3 affinity and bound state lifetime that are each 1 order of magnitude lower than those of the dimeric WT PH domain, which is predicted to facilitate release of activated, monomeric PDK1 to the cytoplasm. Overall, the study yields the first molecular picture of PH domain regulation via electrostatic control of dimer-monomer conversion.

Tetra-primer ARMS-PCR identified four pivotal genetic variations in bovine PNPLA3 gene and its expression patterns.

PubMed

Wang, Zi-nian; Cai, Han-fang; Li, Ming-xun; Cao, Xiu-kai; Lan, Xian-yong; Lei, Chu-zhao; Chen, Hong

2016-01-10

Patatin-like phospholipase domain-containing protein 3 (PNPLA3), a member of the patatin like phospholipase domain-containing (PNPLA) family, plays an important role in energy balance, fat metabolism regulation, glucose metabolism and fatty liver disease. Tetra-primer amplification refractory mutation system PCR (T-ARMS-PCR) is a new method offering fast detection and extreme simplicity at a negligible cost for SNP genotyping. In this paper, we investigated the genetic variations at different ages of 660 Chinese indigenous cattle belonging to three breeds (QC, NY, JX) and applied T-ARMS-PCR and PCR-RFLP methods to genotype four SNPs, SNP1: g.A2980G, SNP2: g.A2996T, SNP3: g.A36718G, SNP4: g.G36850A. The statistical analyses indicated that these 4 SNPs affected growth traits markedly (P<0.05) in QC population, whereas combined haplotypes were not (P>0.05). The qPCR (quantitative PCR) indicated that bovine PNPLA3 gene was exclusively expressed in fat tissues. Besides, the analysis between SNP and mRNA expression revealed that, in SNP1, the expression of AG was much higher than AA and GG (P<0.05), which was in accordance with the results of growth traits association analysis, while the results of SNP4 was not. These results supported high potential that SNPs of bovine PNPLA3 gene might be utilized as genetic markers in marker-assisted selection (MAS) for Chinese cattle breeding programs. Copyright © 2015 Elsevier B.V. All rights reserved.

Decreasing µ142Nd Variation in the Archean Convecting Mantle from 4.0 to 2.5 Ga: Heterogeneous Domain Mixing or Crustal Recycling?

NASA Astrophysics Data System (ADS)

Brandon, A. D.; Debaille, V.

2014-12-01

The 146Sm-142Nd (t1/2=68 Ma) chronometer can be used to examine silicate differentiation in the first 400 Ma of Earth history. Early fractionation between Sm and Nd is recorded in cratonic Archean rocks in their 142Nd/144Nd ratios that that deviate up to ±20 ppm, or μ142Nd - ppm deviation relative to the present-day convecting mantle at 0. These values likely record early extraction of incompatible trace element (ITE) enriched material with -μ142Nd, either as crust or late stage residual melt from a magma ocean, and resulting in a complimentary ITE depleted residual mantle with +μ142Nd. If this early-formed ITE-enriched material was re-incorporated rapidly back into the convecting mantle, both ITE-enriched and ITE-depleted mantle domains would have been established in the Hadean. Alternatively, if it was early-formed crust that remained stable it could have slowly eroded and progressively remixed into the convecting mantle as subducted sediment during the Archean. Each of these scenarios could potentially explain the decrease in the maximum variation in µ142Nd from ±20 at 4.0 Ga to 0 at 2.5 Ga [1,2,3]. In the scenario where these variations reflect mixing of mantle domains, this implies long mantle mixing times of greater than 1 Ga in the Archean in order to preserve the early-formed heterogeneities. This can be achieved in a stagnant lid tectonic regime in the Archean with sporadic and short subduction cycles [2]. This scenario would also indicate that mixing times in the convecting mantle were much slower than the previously proposed 100 Ma in the Hadean and Archean. In the alternative scenario, sediment with -µ142Nd was progressively mixed into the mantle via subduction in the Archean [3]. This scenario doesn't require slow mantle mixing times or a stagnant-lid regime. It requires crustal resident times of up to 750 Ma to maintain a steady supply of ancient sediment recycling over the Archean. Each of these scenarios evoke very contrasting conditions for early Earth history and additional examination is needed. We will consider the geochemical consequences of crustal sediment subduction in order to test the hypothesis of crustal recycling as well as provide additional evidence to aid in resolving this issue. [1] Bennett et al., Science, 318 (2007), p.1907 [2] Debaille et al., EPSL, 373 (2013), p.83 [3] Roth et al., G3, 2014

Moral sensitivity relating to the application of the code of ethics.

PubMed

Kim, Yong-Soon; Kang, Se-Won; Ahn, Jeong-Ah

2013-06-01

This study investigated the clinical application of the 2006 Third Revised Korean Nurses' Code of Ethics and the moral sensitivity of nurses. A total of 303 clinical nurses in South Korea participated in the survey in May and June 2011. As instruments of this study, we used the 15 statements of the Korean Nurses' Code of Ethics and Korean Moral Sensitivity Questionnaire. The mean score for application was 3.77 ± 0.59 (out of 5), and the mean score for moral sensitivity was 5.14 ± 0.55 (out of 7). The correlation coefficient (r) of the application and moral sensitivity was 0.336 (p < 0.001). Nurses who scored high on moral sensitivity also scored high on application (t = -5.018, p < 0.001). In clinical settings, educational programmes to develop the moral sensitivity of nurses are necessary for improving the application of the code of ethics.

SU-C-207A-05: Feature Based Water Equivalent Path Length (WEPL) Determination for Proton Radiography by the Technique of Time Resolved Dose Measurement

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

Zhang, R; Jee, K; Sharp, G

Purpose: Studies show that WEPL can be determined from modulated dose rate functions (DRF). However, the previous calibration method based on statistics of the DRF is sensitive to energy mixing of protons due to scattering through different materials (termed as range mixing here), causing inaccuracies in the determination of WEPL. This study intends to explore time-domain features of the DRF to reduce the effect of range mixing in proton radiography (pRG) by this technique. Methods: An amorphous silicon flat panel (PaxScan™ 4030CB, Varian Medical Systems, Inc., Palo Alto, CA) was placed behind phantoms to measure DRFs from a proton beammore » modulated by a specially designed modulator wheel. The performance of two methods, the previously used method based on the root mean square (RMS) and the new approach based on time-domain features of the DRF, are compared for retrieving WEPL and RSP from pRG of a Gammex phantom. Results: Calibration by T{sub 80} (the time point for 80% of the major peak) was more robust to range mixing and produced WEPL with improved accuracy. The error of RSP was reduced from 8.2% to 1.7% for lung equivalent material, with the mean error for all other materials reduced from 1.2% to 0.7%. The mean error of the full width at half maximum (FWHM) of retrieved inserts was decreased from 25.85% to 5.89% for the RMS and T{sub 80} method respectively. Monte Carlo simulations in simplified cases also demonstrated that the T{sub 80} method is less sensitive to range mixing than the RMS method. Conclusion: WEPL images have been retrieved based on single flat panel measured DRFs, with inaccuracies reduced by exploiting time-domain features as the calibration parameter. The T{sub 80} method is validated to be less sensitive to range mixing and can thus retrieve the WEPL values in proximity of interfaces with improved numerical and spatial accuracy for proton radiography.« less

CUDA Fortran acceleration for the finite-difference time-domain method

NASA Astrophysics Data System (ADS)

Hadi, Mohammed F.; Esmaeili, Seyed A.

2013-05-01

A detailed description of programming the three-dimensional finite-difference time-domain (FDTD) method to run on graphical processing units (GPUs) using CUDA Fortran is presented. Two FDTD-to-CUDA thread-block mapping designs are investigated and their performances compared. Comparative assessment of trade-offs between GPU's shared memory and L1 cache is also discussed. This presentation is for the benefit of FDTD programmers who work exclusively with Fortran and are reluctant to port their codes to C in order to utilize GPU computing. The derived CUDA Fortran code is compared with an optimized CPU version that runs on a workstation-class CPU to present a realistic GPU to CPU run time comparison and thus help in making better informed investment decisions on FDTD code redesigns and equipment upgrades. All analyses are mirrored with CUDA C simulations to put in perspective the present state of CUDA Fortran development.

Risk perception influences athletic pacing strategy.

PubMed

Micklewright, Dominic; Parry, David; Robinson, Tracy; Deacon, Greg; Renfree, Andrew; St Clair Gibson, Alan; Matthews, William J

2015-05-01

The objective of this study is to examine risk taking and risk perception associations with perceived exertion, pacing, and performance in athletes. Two experiments were conducted in which risk perception was assessed using the domain-specific risk taking (DOSPERT) scale in 20 novice cyclists (experiment 1) and 32 experienced ultramarathon runners (experiment 2). In experiment 1, participants predicted their pace and then performed a 5-km maximum effort cycling time trial on a calibrated Kingcycle mounted bicycle. Split times and perceived exertion were recorded every kilometer. In experiment 2, each participant predicted their split times before running a 100-km ultramarathon. Split times and perceived exertion were recorded at seven checkpoints. In both experiments, higher and lower risk perception groups were created using median split of DOSPERT scores. In experiment 1, pace during the first kilometer was faster among lower risk perceivers compared with higher risk perceivers (t(18) = 2.0, P = 0.03) and faster among higher risk takers compared with lower risk takers (t(18) = 2.2, P = 0.02). Actual pace was slower than predicted pace during the first kilometer in both the higher risk perceivers (t(9) = -4.2, P = 0.001) and lower risk perceivers (t(9) = -1.8, P = 0.049). In experiment 2, pace during the first 36 km was faster among lower risk perceivers compared with higher risk perceivers (t(16) = 2.0, P = 0.03). Irrespective of risk perception group, actual pace was slower than predicted pace during the first 18 km (t(16) = 8.9, P < 0.001) and from 18 to 36 km (t(16) = 4.0, P < 0.001). In both experiments, there was no difference in performance between higher and lower risk perception groups. Initial pace is associated with an individual's perception of risk, with low perceptions of risk being associated with a faster starting pace. Large differences between predicted and actual pace suggest that the performance template lacks accuracy, perhaps indicating greater reliance on momentary pacing decisions rather than preplanned strategy.

A phase transition in the first passage of a Brownian process through a fluctuating boundary with implications for neural coding.

PubMed

Taillefumier, Thibaud; Magnasco, Marcelo O

2013-04-16

Finding the first time a fluctuating quantity reaches a given boundary is a deceptively simple-looking problem of vast practical importance in physics, biology, chemistry, neuroscience, economics, and industrial engineering. Problems in which the bound to be traversed is itself a fluctuating function of time include widely studied problems in neural coding, such as neuronal integrators with irregular inputs and internal noise. We show that the probability p(t) that a Gauss-Markov process will first exceed the boundary at time t suffers a phase transition as a function of the roughness of the boundary, as measured by its Hölder exponent H. The critical value occurs when the roughness of the boundary equals the roughness of the process, so for diffusive processes the critical value is Hc = 1/2. For smoother boundaries, H > 1/2, the probability density is a continuous function of time. For rougher boundaries, H < 1/2, the probability is concentrated on a Cantor-like set of zero measure: the probability density becomes divergent, almost everywhere either zero or infinity. The critical point Hc = 1/2 corresponds to a widely studied case in the theory of neural coding, in which the external input integrated by a model neuron is a white-noise process, as in the case of uncorrelated but precisely balanced excitatory and inhibitory inputs. We argue that this transition corresponds to a sharp boundary between rate codes, in which the neural firing probability varies smoothly, and temporal codes, in which the neuron fires at sharply defined times regardless of the intensity of internal noise.

Barriers and enablers to the delivery of psychological care in the management of patients with type 2 diabetes mellitus in China: a qualitative study using the theoretical domains framework.

PubMed

Chapman, Anna; Yang, Hui; Thomas, Shane A; Searle, Kendall; Browning, Colette

2016-03-29

China has the largest number of type 2 diabetes mellitus (T2DM) cases globally and individuals with T2DM have an increased risk of developing mental health disorders and functional problems. Despite guidelines recommending that psychological care be delivered in conjunction with standard T2DM care; psychological care is not routinely delivered in China. Community Health Centre (CHC) doctors play a key role in the management of patients with T2DM in China. Understanding the behavioural determinants of CHC doctors in the implementation of psychological care recommendations allows for the design of targeted and culturally appropriate interventions. As such, this study aimed to examine barriers and enablers to the delivery of psychological care to patients with T2DM from the perspective of CHC doctors in China. Two focus groups were conducted with 23 CHC doctors from Shenzhen, China. The discussion guide applied the Theoretical Domains Framework (TDF) that examines current practice and identifies key barriers and enablers perceived to influence practice. Focus groups were conducted with an interpreter, and were digitally recorded and transcribed. Two researchers independently coded transcripts into pre-defined themes using deductive thematic analysis. Barriers and enablers perceived by doctors as being relevant to the delivery of psychological care for patients with T2DM were primarily categorised within eight TDF domains. Key barriers included: CHC doctors' knowledge and skills; time constraints; and absence of financial incentives. Other barriers included: societal perception that treating psychological aspects of health is less important than physical health; lack of opinion leaders; doctors' intentional disregard of psychological care; and doubts regarding the efficacy of psychological care. In contrast, perceived enablers included: training of CHC doctors in psychological skills; identification of afternoon/evening clinic times when recommendations could be implemented; introduction of financial incentives; and the creation of a professional role (e.g. diabetes educator), that could implement psychological care recommendations to patients with T2DM. The utilisation of the TDF allowed for the comprehensive understanding of barriers and enablers to the implementation of psychological care recommendations for patients with T2DM, and consequently, has given direction to future interventions strategies aimed at improving the implementation of such recommendations.

Optical digital chaos cryptography

NASA Astrophysics Data System (ADS)

Arenas-Pingarrón, Álvaro; González-Marcos, Ana P.; Rivas-Moscoso, José M.; Martín-Pereda, José A.

2007-10-01

In this work we present a new way to mask the data in a one-user communication system when direct sequence - code division multiple access (DS-CDMA) techniques are used. The code is generated by a digital chaotic generator, originally proposed by us and previously reported for a chaos cryptographic system. It is demonstrated that if the user's data signal is encoded with a bipolar phase-shift keying (BPSK) technique, usual in DS-CDMA, it can be easily recovered from a time-frequency domain representation. To avoid this situation, a new system is presented in which a previous dispersive stage is applied to the data signal. A time-frequency domain analysis is performed, and the devices required at the transmitter and receiver end, both user-independent, are presented for the optical domain.

The element level time domain (ELTD) method for the analysis of nano-optical systems: I. Nondispersive media

NASA Astrophysics Data System (ADS)

Fallahi, Arya; Oswald, Benedikt; Leidenberger, Patrick

2012-04-01

We study a 3-dimensional, dual-field, fully explicit method for the solution of Maxwell's equations in the time domain on unstructured, tetrahedral grids. The algorithm uses the element level time domain (ELTD) discretization of the electric and magnetic vector wave equations. In particular, the suitability of the method for the numerical analysis of nanometer structured systems in the optical region of the electromagnetic spectrum is investigated. The details of the theory and its implementation as a computer code are introduced and its convergence behavior as well as conditions for stable time domain integration is examined. Here, we restrict ourselves to non-dispersive dielectric material properties since dielectric dispersion will be treated in a subsequent paper. Analytically solvable problems are analyzed in order to benchmark the method. Eventually, a dielectric microlens is considered to demonstrate the potential of the method. A flexible method of 2nd order accuracy is obtained that is applicable to a wide range of nano-optical configurations and can be a serious competitor to more conventional finite difference time domain schemes which operate only on hexahedral grids. The ELTD scheme can resolve geometries with a wide span of characteristic length scales and with the appropriate level of detail, using small tetrahedra where delicate, physically relevant details must be modeled.

Axisymmetric Implementation for 3D-Based DSMC Codes

NASA Technical Reports Server (NTRS)

Stewart, Benedicte; Lumpkin, F. E.; LeBeau, G. J.

2011-01-01

The primary objective in developing NASA s DSMC Analysis Code (DAC) was to provide a high fidelity modeling tool for 3D rarefied flows such as vacuum plume impingement and hypersonic re-entry flows [1]. The initial implementation has been expanded over time to offer other capabilities including a novel axisymmetric implementation. Because of the inherently 3D nature of DAC, this axisymmetric implementation uses a 3D Cartesian domain and 3D surfaces. Molecules are moved in all three dimensions but their movements are limited by physical walls to a small wedge centered on the plane of symmetry (Figure 1). Unfortunately, far from the axis of symmetry, the cell size in the direction perpendicular to the plane of symmetry (the Z-direction) may become large compared to the flow mean free path. This frequently results in inaccuracies in these regions of the domain. A new axisymmetric implementation is presented which aims to solve this issue by using Bird s approach for the molecular movement while preserving the 3D nature of the DAC software [2]. First, the computational domain is similar to that previously used such that a wedge must still be used to define the inflow surface and solid walls within the domain. As before molecules are created inside the inflow wedge triangles but they are now rotated back to the symmetry plane. During the move step, molecules are moved in 3D but instead of interacting with the wedge walls, the molecules are rotated back to the plane of symmetry at the end of the move step. This new implementation was tested for multiple flows over axisymmetric shapes, including a sphere, a cone, a double cone and a hollow cylinder. Comparisons to previous DSMC solutions and experiments, when available, are made.

Performance of a parallel thermal-hydraulics code TEMPEST

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

Fann, G.I.; Trent, D.S.

The authors describe the parallelization of the Tempest thermal-hydraulics code. The serial version of this code is used for production quality 3-D thermal-hydraulics simulations. Good speedup was obtained with a parallel diagonally preconditioned BiCGStab non-symmetric linear solver, using a spatial domain decomposition approach for the semi-iterative pressure-based and mass-conserved algorithm. The test case used here to illustrate the performance of the BiCGStab solver is a 3-D natural convection problem modeled using finite volume discretization in cylindrical coordinates. The BiCGStab solver replaced the LSOR-ADI method for solving the pressure equation in TEMPEST. BiCGStab also solves the coupled thermal energy equation. Scalingmore » performance of 3 problem sizes (221220 nodes, 358120 nodes, and 701220 nodes) are presented. These problems were run on 2 different parallel machines: IBM-SP and SGI PowerChallenge. The largest problem attains a speedup of 68 on an 128 processor IBM-SP. In real terms, this is over 34 times faster than the fastest serial production time using the LSOR-ADI solver.« less

Mutations of the RTEL1 Helicase in a Hoyeraal-Hreidarsson Syndrome Patient Highlight the Importance of the ARCH Domain.

PubMed

Jullien, Laurent; Kannengiesser, Caroline; Kermasson, Laetitia; Cormier-Daire, Valérie; Leblanc, Thierry; Soulier, Jean; Londono-Vallejo, Arturo; de Villartay, Jean-Pierre; Callebaut, Isabelle; Revy, Patrick

2016-05-01

The DNA helicase RTEL1 participates in telomere maintenance and genome stability. Biallelic mutations in the RTEL1 gene account for the severe telomere biology disorder characteristic of the Hoyeraal-Hreidarsson syndrome (HH). Here, we report a HH patient (P4) carrying two novel compound heterozygous mutations in RTEL1: a premature stop codon (c.949A>T, p.Lys317*) and an intronic deletion leading to an exon skipping and an in-frame deletion of 25 amino-acids (p.Ile398_Lys422). P4's cells exhibit short and dysfunctional telomeres similarly to other RTEL1-deficient patients. 3D structure predictions indicated that the p.Ile398_Lys422 deletion affects a part of the helicase ARCH domain, which lines the pore formed with the core HD and the iron-sulfur cluster domains and is highly specific of sequences from the eukaryotic XPD family members. © 2016 WILEY PERIODICALS, INC.

Impairment of different protein domains causes variable clinical presentation within Pitt-Hopkins syndrome and suggests intragenic molecular syndromology of TCF4.

PubMed

Bedeschi, Maria Francesca; Marangi, Giuseppe; Calvello, Maria Rosaria; Ricciardi, Stefania; Leone, Francesca Pia Chiara; Baccarin, Marco; Guerneri, Silvana; Orteschi, Daniela; Murdolo, Marina; Lattante, Serena; Frangella, Silvia; Keena, Beth; Harr, Margaret H; Zackai, Elaine; Zollino, Marcella

2017-11-01

Pitt-Hopkins syndrome is a neurodevelopmental disorder characterized by severe intellectual disability and a distinctive facial gestalt. It is caused by haploinsufficiency of the TCF4 gene. The TCF4 protein has different functional domains, with the NLS (nuclear localization signal) domain coded by exons 7-8 and the bHLH (basic Helix-Loop-Helix) domain coded by exon 18. Several alternatively spliced TCF4 variants have been described, allowing for translation of variable protein isoforms. Typical PTHS patients have impairment of at least the bHLH domain. To which extent impairment of the remaining domains contributes to the final phenotype is not clear. There is recent evidence that certain loss-of-function variants disrupting TCF4 are associated with mild ID, but not with typical PTHS. We describe a frameshift-causing partial gene deletion encompassing exons 4-6 of TCF4 in an adult patient with mild ID and nonspecific facial dysmorphisms but without the typical features of PTHS, and a c.520C > T nonsense variant within exon 8 in a child presenting with a severe phenotype largely mimicking PTHS, but lacking the typical facial dysmorphism. Investigation on mRNA, along with literature review, led us to suggest a preliminary phenotypic map of loss-of-function variants affecting TCF4. An intragenic phenotypic map of loss-of-function variants in TCF4 is suggested here for the first time: variants within exons 1-4 and exons 4-6 give rise to a recurrent phenotype with mild ID not in the spectrum of Pitt-Hopkins syndrome (biallelic preservation of both the NLS and bHLH domains); variants within exons 7-8 cause a severe phenotype resembling PTHS but in absence of the typical facial dysmorphism (impairment limited to the NLS domain); variants within exons 9-19 cause typical Pitt-Hopkins syndrome (impairment of at least the bHLH domain). Understanding the TCF4 molecular syndromology can allow for proper nosology in the current era of whole genomic investigations. Copyright © 2017. Published by Elsevier Masson SAS.

Single Airfoil Gust Response Problem: Category 3, Problem 1

NASA Technical Reports Server (NTRS)

Scott, James R.

2004-01-01

An unsteady aerodynamic code, called GUST3D (ref. 3), has been developed to solve equation (8) for flows with periodic vortical disturbances. The code uses a frequency-domain approach with second-order central differences and a pressure radiation condition in the far field. GUST3D requires as input certain mean flow quantities which are calculated separately by a potential flow solver. The solver calculates the mean ow using a Gothert's Rule approximation (ref. 3). On the airfoil surface, it uses the solution calculated by the potential code FLO36 (ref. 4). Figures 1-2 show the mean pressure along the airfoil surface for the two airfoil geometries. In Figures 3 - 8, we present the RMS pressure on the airfoil surface. Each figure shows three GUST3D solutions (calculated on grids with different far-field boundary locations). Three solutions are shown to provide some indication of the numerical uncertainty in the results. Figures 9 - 13 present the acoustic intensity. We again show three solutions per case. Note that no results are presented for the k1 = k2 = 2.0 loaded airfoil case, as an acceptable solution could not be obtained. A few comments need to be made about the results shown. First, since the last Workshop, the GUST3D code has been substantially upgraded. This includes implementing a more accurate far-field boundary condition (ref. 5) and developing improved gridding capabilities. This is the reason for any differences that may exist between the present results and results from the last Workshop. Second, the intensity results on the circle R = 4C were obtained using a Kirchoff method (ref. 6). The Kirchoff surface was the circle R = 2C. Finally, the GUST3D code is most accurate for low reduced frequencies. A new domain decomposition approach (ref. 7) has been developed to improve accuracy. Both the single domain and domain decomposition approaches were used in generating the present results.

Slow dynamics of a protein backbone in molecular dynamics simulation revealed by time-structure based independent component analysis

NASA Astrophysics Data System (ADS)

Naritomi, Yusuke; Fuchigami, Sotaro

2013-12-01

We recently proposed the method of time-structure based independent component analysis (tICA) to examine the slow dynamics involved in conformational fluctuations of a protein as estimated by molecular dynamics (MD) simulation [Y. Naritomi and S. Fuchigami, J. Chem. Phys. 134, 065101 (2011)]. Our previous study focused on domain motions of the protein and examined its dynamics by using rigid-body domain analysis and tICA. However, the protein changes its conformation not only through domain motions but also by various types of motions involving its backbone and side chains. Some of these motions might occur on a slow time scale: we hypothesize that if so, we could effectively detect and characterize them using tICA. In the present study, we investigated slow dynamics of the protein backbone using MD simulation and tICA. The selected target protein was lysine-, arginine-, ornithine-binding protein (LAO), which comprises two domains and undergoes large domain motions. MD simulation of LAO in explicit water was performed for 1 μs, and the obtained trajectory of Cα atoms in the backbone was analyzed by tICA. This analysis successfully provided us with slow modes for LAO that represented either domain motions or local movements of the backbone. Further analysis elucidated the atomic details of the suggested local motions and confirmed that these motions truly occurred on the expected slow time scale.

The tetramerization domain potentiates Kv4 channel function by suppressing closed-state inactivation.

PubMed

Tang, Yi-Quan; Zhou, Jing-Heng; Yang, Fan; Zheng, Jie; Wang, KeWei

2014-09-02

A-type Kv4 potassium channels undergo a conformational change toward a nonconductive state at negative membrane potentials, a dynamic process known as pre-open closed states or closed-state inactivation (CSI). CSI causes inhibition of channel activity without the prerequisite of channel opening, thus providing a dynamic regulation of neuronal excitability, dendritic signal integration, and synaptic plasticity at resting. However, the structural determinants underlying Kv4 CSI remain largely unknown. We recently showed that the auxiliary KChIP4a subunit contains an N-terminal Kv4 inhibitory domain (KID) that directly interacts with Kv4.3 channels to enhance CSI. In this study, we utilized the KChIP4a KID to probe key structural elements underlying Kv4 CSI. Using fluorescence resonance energy transfer two-hybrid mapping and bimolecular fluorescence complementation-based screening combined with electrophysiology, we identified the intracellular tetramerization (T1) domain that functions to suppress CSI and serves as a receptor for the binding of KID. Disrupting the Kv4.3 T1-T1 interaction interface by mutating C110A within the C3H1 motif of T1 domain facilitated CSI and ablated the KID-mediated enhancement of CSI. Furthermore, replacing the Kv4.3 T1 domain with the T1 domain from Kv1.4 (without the C3H1 motif) or Kv2.1 (with the C3H1 motif) resulted in channels functioning with enhanced or suppressed CSI, respectively. Taken together, our findings reveal a novel (to our knowledge) role of the T1 domain in suppressing Kv4 CSI, and that KChIP4a KID directly interacts with the T1 domain to facilitate Kv4.3 CSI, thus leading to inhibition of channel function. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Reaction time and anticipatory skill of athletes in open and closed skill-dominated sport.

PubMed

Nuri, Leila; Shadmehr, Azadeh; Ghotbi, Nastaran; Attarbashi Moghadam, Behrouz

2013-01-01

In sports, reaction time and anticipatory skill are critical aspects of perceptual abilities. To date, no study has compared reaction time and anticipatory skill of athletes from open and closed skill-dominated sport. Accordingly, the present study investigated whether a difference exists in sensory-cognitive skills between these two different sport domains. Eleven volleyball players and 11 sprinters participated in this experiment. Reaction time and anticipatory skill of both groups were recorded by a custom-made software called SART (speed anticipation and reaction time test). This software consists of six sensory-cognitive tests that evaluate visual choice reaction time, visual complex choice reaction time, auditory choice reaction time, auditory complex choice reaction time, and anticipatory skill of the high speed and low speed of the ball. For each variable, an independent t-test was performed. Results suggested that sprinters were better in both auditory reaction times (P<0.001 for both tests) and volleyball players were better in both anticipatory skill tests (P = 0.007 and P = 0.04 for anticipatory skill of the high speed and low speed of the ball, respectively). However, no significant differences were found in both visual choice reaction time tests (P > 0.05 for both visual reaction time tests). It is concluded that athletes have greater sensory-cognitive skills related to their specific sport domain either open or closed.

Coupling MHD and PIC models in 2 dimensions

NASA Astrophysics Data System (ADS)

Daldorff, L.; Toth, G.; Sokolov, I.; Gombosi, T. I.; Lapenta, G.; Brackbill, J. U.; Markidis, S.; Amaya, J.

2013-12-01

Even for extended fluid plasma models, like Hall, anisotropic ion pressure and multi fluid MHD, there are still many plasma phenomena that are not well captured. For this reason, we have coupled the Implicit Particle-In-Cell (iPIC3D) code with the BATSRUS global MHD code. The PIC solver is applied in a part of the computational domain, for example, in the vicinity of reconnection sites, and overwrites the MHD solution. On the other hand, the fluid solver provides the boundary conditions for the PIC code. To demonstrate the use of the coupled codes for magnetospheric applications, we perform a 2D magnetosphere simulation, where BATSRUS solves for Hall MHD in the whole domain except for the tail reconnection region, which is handled by iPIC3D.

Visco-elastic controlled-source full waveform inversion without surface waves

NASA Astrophysics Data System (ADS)

Paschke, Marco; Krause, Martin; Bleibinhaus, Florian

2016-04-01

We developed a frequency-domain visco-elastic full waveform inversion for onshore seismic experiments with topography. The forward modeling is based on a finite-difference time-domain algorithm by Robertsson that uses the image-method to ensure a stress-free condition at the surface. The time-domain data is Fourier-transformed at every point in the model space during the forward modeling for a given set of frequencies. The motivation for this approach is the reduced amount of memory when computing kernels, and the straightforward implementation of the multiscale approach. For the inversion, we calculate the Frechet derivative matrix explicitly, and we implement a Levenberg-Marquardt scheme that allows for computing the resolution matrix. To reduce the size of the Frechet derivative matrix, and to stabilize the inversion, an adapted inverse mesh is used. The node spacing is controlled by the velocity distribution and the chosen frequencies. To focus the inversion on body waves (P, P-coda, and S) we mute the surface waves from the data. Consistent spatiotemporal weighting factors are applied to the wavefields during the Fourier transform to obtain the corresponding kernels. We test our code with a synthetic study using the Marmousi model with arbitrary topography. This study also demonstrates the importance of topography and muting surface waves in controlled-source full waveform inversion.

RNAP-II transcribes two small RNAs at the promoter and terminator regions of the RNAP-I gene in Saccharomyces cerevisiae.

PubMed

Mayán, Maria D

2013-01-01

Three RNA polymerases coexist in the ribosomal DNA of Saccharomyces cerevisiae. RNAP-I transcribes the 35S rRNA, RNAP-III transcribes the 5S rRNA and RNAP-II is found in both intergenic non-coding regions. Previously, we demonstrated that RNAP-II molecules bound to the intergenic non-coding regions (IGS) of the ribosomal locus are mainly found in a stalled conformation, and the stalled polymerase mediates chromatin interactions, which isolate RNAP-I from the RNAP-III transcriptional domain. Besides, RNAP-II transcribes both IGS regions at low levels, using different cryptic promoters. This report demonstrates that RNAP-II also transcribes two sequences located in the 5'- and 3'-ends of the 35S rRNA gene that overlap with the sequences of the 35S rRNA precursor transcribed by RNAP-I. The sequence located at the promoter region of RNAP-I, called the p-RNA transcript, binds to the transcription termination-related protein, Reb1p, while the T-RNA sequence, located in the termination sites of RNAP-I gene, contains the stem-loop recognized by Rtn1p, which is necessary for proper termination of RNAP-I. Because of their location, these small RNAs may play a key role in the initiation and termination of RNAP-I transcription. To correctly synthesize proteins, eukaryotic cells may retain a mechanism that connects the three main polymerases. This report suggests that cryptic transcription by RNAP-II may be required for normal transcription by RNAP-I in the ribosomal locus of S. cerevisiae. Copyright © 2012 John Wiley & Sons, Ltd.

Human Th17 Migration in Three-Dimensional Collagen Involves p38 MAPK.

PubMed

Kadiri, Maleck; El Azreq, Mohammed-Amine; Berrazouane, Sofiane; Boisvert, Marc; Aoudjit, Fawzi

2017-09-01

T cell migration across extracellular matrix (ECM) is an important step of the adaptive immune response but is also involved in the development of inflammatory autoimmune diseases. Currently, the molecular mechanisms regulating the motility of effector T cells in ECM are not fully understood. Activation of p38 MAPK has been implicated in T cell activation and is critical to the development of immune and inflammatory responses. In this study, we examined the implication of p38 MAPK in regulating the migration of human Th17 cells through collagen. Using specific inhibitor and siRNA, we found that p38 is necessary for human Th17 migration in three-dimensional (3D) collagen and that 3D collagen increases p38 phosphorylation. We also provide evidence that the collagen receptor, discoidin domain receptor 1 (DDR1), which promotes Th17 migration in 3D collagen, is involved in p38 activation. Together, our findings suggest that targeting DDR1/p38 MAPK pathway could be beneficial for the treatment of Th17-mediated inflammatory diseases. J. Cell. Biochem. 118: 2819-2827, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

The complete mitogenome of Ginkgo-toothed beaked whale (Mesoplodon ginkgodens) (Chordata: Ziphiidae).

PubMed

Yao, Chiou-Ju; Chen, Ching-Hung; Hsiao, Chung-Der

2016-07-01

In this study, we used the next-generation sequencing method to deduce the complete mitogenome of Ginkgo-toothed beaked whale (Mesoplodon ginkgodens) for the first time. The nucleotide composition was asymmetric (33.3% A, 25.3% C, 12.6% G, and 28.7% T) with an overall GC content of 37.9%. The length of the assembled mitogenome was 16,339 bp and follows the typical vertebrate arrangement, including 13 protein coding genes, 22 transfer RNAs, 2 ribosomal RNAs genes, and a non-coding control region of D-loop. The D-loop contains 870 bp and is located between tRNA-Pro and tRNA-Phe. The complete mitogenome of Ginkgo-toothed beaked whale deduced in this study provides essential and important DNA molecular data for further phylogenetic and evolutionary analysis for cetaceans.

Fully 3D modeling of tokamak vertical displacement events with realistic parameters

NASA Astrophysics Data System (ADS)

Pfefferle, David; Ferraro, Nathaniel; Jardin, Stephen; Bhattacharjee, Amitava

2016-10-01

In this work, we model the complex multi-domain and highly non-linear physics of Vertical Displacement Events (VDEs), one of the most damaging off-normal events in tokamaks, with the implicit 3D extended MHD code M3D-C1. The code has recently acquired the capability to include finite thickness conducting structures within the computational domain. By exploiting the possibility of running a linear 3D calculation on top of a non-linear 2D simulation, we monitor the non-axisymmetric stability and assess the eigen-structure of kink modes as the simulation proceeds. Once a stability boundary is crossed, a fully 3D non-linear calculation is launched for the remainder of the simulation, starting from an earlier time of the 2D run. This procedure, along with adaptive zoning, greatly increases the efficiency of the calculation, and allows to perform VDE simulations with realistic parameters and high resolution. Simulations are being validated with NSTX data where both axisymmetric (toroidally averaged) and non-axisymmetric induced and conductive (halo) currents have been measured. This work is supported by US DOE Grant DE-AC02-09CH11466.

Sequence analysis of RNase MRP RNA reveals its origination from eukaryotic RNase P RNA

PubMed Central

Zhu, Yanglong; Stribinskis, Vilius; Ramos, Kenneth S.; Li, Yong

2006-01-01

RNase MRP is a eukaryote-specific endoribonuclease that generates RNA primers for mitochondrial DNA replication and processes precursor rRNA. RNase P is a ubiquitous endoribonuclease that cleaves precursor tRNA transcripts to produce their mature 5′ termini. We found extensive sequence homology of catalytic domains and specificity domains between their RNA subunits in many organisms. In Candida glabrata, the internal loop of helix P3 is 100% conserved between MRP and P RNAs. The helix P8 of MRP RNA from microsporidia Encephalitozoon cuniculi is identical to that of P RNA. Sequence homology can be widely spread over the whole molecule of MRP RNA and P RNA, such as those from Dictyostelium discoideum. These conserved nucleotides between the MRP and P RNAs strongly support the hypothesis that the MRP RNA is derived from the P RNA molecule in early eukaryote evolution. PMID:16540690

EssC: domain structures inform on the elusive translocation channel in the Type VII secretion system

PubMed Central

Zoltner, Martin; Ng, Wui M.A.V.; Money, Jillian J.; Fyfe, Paul K.; Kneuper, Holger; Palmer, Tracy; Hunter, William N.

2016-01-01

The membrane-bound protein EssC is an integral component of the bacterial Type VII secretion system (T7SS), which is a determinant of virulence in important Gram-positive pathogens. The protein is predicted to consist of an intracellular repeat of forkhead-associated (FHA) domains at the N-terminus, two transmembrane helices and three P-loop-containing ATPase-type domains, D1–D3, forming the C-terminal intracellular segment. We present crystal structures of the N-terminal FHA domains (EssC-N) and a C-terminal fragment EssC-C from Geobacillus thermodenitrificans, encompassing two of the ATPase-type modules, D2 and D3. Module D2 binds ATP with high affinity whereas D3 does not. The EssC-N and EssC-C constructs are monomeric in solution, but the full-length recombinant protein, with a molecular mass of approximately 169 kDa, forms a multimer of approximately 1 MDa. The observation of protomer contacts in the crystal structure of EssC-C together with similarity to the DNA translocase FtsK, suggests a model for a hexameric EssC assembly. Such an observation potentially identifies the key, and to date elusive, component of pore formation required for secretion by this recently discovered secretion system. The juxtaposition of the FHA domains suggests potential for interacting with other components of the secretion system. The structural data were used to guide an analysis of which domains are required for the T7SS machine to function in pathogenic Staphylococcus aureus. The extreme C-terminal ATPase domain appears to be essential for EssC activity as a key part of the T7SS, whereas D2 and FHA domains are required for the production of a stable and functional protein. PMID:27130157

Random oligonucleotide mutagenesis: application to a large protein coding sequence of a major histocompatibility complex class I gene, H-2DP.

PubMed Central

Murray, R; Pederson, K; Prosser, H; Muller, D; Hutchison, C A; Frelinger, J A

1988-01-01

We have used random oligonucleotide mutagenesis (or saturation mutagenesis) to create a library of point mutations in the alpha 1 protein domain of a Major Histocompatibility Complex (MHC) molecule. This protein domain is critical for T cell and B cell recognition. We altered the MHC class I H-2DP gene sequence such that synthetic mutant alpha 1 exons (270 bp of coding sequence), which contain mutations identified by sequence analysis, can replace the wild type alpha 1 exon. The synthetic exons were constructed from twelve overlapping oligonucleotides which contained an average of 1.3 random point mutations per intact exon. DNA sequence analysis of mutant alpha 1 exons has shown a point mutant distribution that fits a Poisson distribution, and thus emphasizes the utility of this mutagenesis technique to "scan" a large protein sequence for important mutations. We report our use of saturation mutagenesis to scan an entire exon of the H-2DP gene, a cassette strategy to replace the wild type alpha 1 exon with individual mutant alpha 1 exons, and analysis of mutant molecules expressed on the surface of transfected mouse L cells. Images PMID:2903482

Ruminal acidosis challenge impact on ruminal temperature in feedlot cattle.

PubMed

Wahrmund, J L; Ronchesel, J R; Krehbiel, C R; Goad, C L; Trost, S M; Richards, C J

2012-08-01

The objective of this experiment was to determine if ruminal temperature rise coincides with pH reduction using an acidosis challenge model. Twelve ruminally cannulated steers (518 ± 28 kg BW) were administered ruminal temperature-monitoring devices that recorded temperature every 2 min. Steers were fed a 63% concentrate diet at 1.6% BW for 20 d before being randomly assigned to 1 of 3 acidosis challenge treatments: no dietary change (CON), one-half of daily DMI replaced with cracked corn (HALF), or all of daily DMI replaced with cracked corn (CORN). The challenge was initiated by ruminally dosing steers with their treatment diets. Ruminal pH and rectal temperatures (T(rec)) were recorded every 3 h for 72 h. All steers were offered CON diets at 24 and 48 h after challenge. Ruminal pH showed a treatment × day effect (P = 0.01). Ruminal pH of CORN steers was lower (P = 0.03) than that of HALF steers on d 1, was lower (P ≤ 0.004) than that of HALF and CON steers on d 2, and tended to be lower (P ≤ 0.10) than that of HALF and CON steers on d 3. Treatment did not affect (P ≥ 0.42) RecT. Ruminal temperature (T(rum)) showed a treatment · d(-1) · h(-1) after feeding interaction (P < 0.01). At 3 h after challenge, T(rum) of CORN and HALF steers was higher (P ≤ 0.01) than that of CON steers. On d 2, T(rum) of CORN steers was higher (P ≤ 0.03) than that of CON between 6 and 12 h after feeding. From 15 to 21 h after feeding on d 2, T(rum) of HALF steers was higher (P < 0.01) than that of CORN and CON steers. On d 3, at the time of feeding until 3 h later, T(rum) of CORN steers was lower (P ≤ 0.04) than that of all other steers. Rectal temperature was correlated (P ≤ 0.01) with T(rum) on all days for CON and CORN steers. Ruminal pH was negatively correlated (P ≤ 0.04) with T(rec) on d 2 and T(rum) on d 1 in CORN steers, and T(rum) was negatively correlated (P ≤ 0.02) with ruminal pH in HALF and CON steers on d 1 and 3, respectively. The amount of time above T(rum) of 39.0°C or 39.45°C was correlated (P ≤ 0.05) with the time spent below a ruminal pH of 5.5 in CORN steers; however, time above T(rum) of 39.0°C did not differ (P = 0.87) among treatments. Results indicate that there is a negative relationship between T(rum) and ruminal pH during an acidotic episode; therefore, T(rum) monitoring can detect a potential acidotic episode.

Continuous positive airway pressure deepens sleep in patients with Alzheimer's disease and obstructive sleep apnea

PubMed Central

Cooke, Jana R.; Ancoli-Israel, Sonia; Liu, Lianqi; Loredo, Jose S.; Natarajan, Loki; Palmer, Barton S.; He, Feng; Corey-Bloom, Jody

2009-01-01

Objective Patients with Alzheimer's disease (AD) and obstructive sleep apnea (OSA) experience disrupted sleep. This study examined the effect of continuous positive airway pressure (CPAP) on sleep parameters in AD patients with OSA. Methods A randomized placebo-controlled trial of 3 weeks of therapeutic CPAP (tCPAP) vs. 3 weeks placebo CPAP (pCPAP) followed by 3 weeks tCPAP in patients with AD and OSA. Polysomnography data from screening after one night and after three weeks of treatment were analyzed. Records were scored for percent of each sleep stage, total sleep time (TST), sleep efficiency (SE), sleep period (SP), time in bed (TIB), sleep onset (SO), wake time after sleep onset (WASO), and arousals. A randomized design comparing one night of pCPAP to tCPAP and a paired analysis combining 3 weeks of tCPAP were performed. Results Fifty-two participants (mean age=77.8 years, SD=7.3) with AD and OSA were included. After one treatment night, the tCPAP group had significantly less % Stage 1 (p=0.04) and more % Stage 2 sleep (p=0.02) when compared to the pCPAP group. In the paired analysis, 3-weeks of tCPAP resulted in significant decreases in WASO (p=0.005), % Stage 1 (p=0.001), arousals (p=0.005), and in an increase in % Stage 3 (p=0.006). Conclusion In mild to moderate AD patients with OSA, the use of tCPAP resulted in deeper sleep after just one night, with improvements maintained for three weeks. PMID:19699148

TREM2 is associated with increased risk for Alzheimer's disease in African Americans.

PubMed

Jin, Sheng Chih; Carrasquillo, Minerva M; Benitez, Bruno A; Skorupa, Tara; Carrell, David; Patel, Dwani; Lincoln, Sarah; Krishnan, Siddharth; Kachadoorian, Michaela; Reitz, Christiane; Mayeux, Richard; Wingo, Thomas S; Lah, James J; Levey, Allan I; Murrell, Jill; Hendrie, Hugh; Foroud, Tatiana; Graff-Radford, Neill R; Goate, Alison M; Cruchaga, Carlos; Ertekin-Taner, Nilüfer

2015-04-10

TREM2 encodes for triggering receptor expressed on myeloid cells 2 and has rare, coding variants that associate with risk for late-onset Alzheimer's disease (LOAD) in Caucasians of European and North-American origin. This study evaluated the role of TREM2 in LOAD risk in African-American (AA) subjects. We performed exonic sequencing and validation in two independent cohorts of >800 subjects. We selected six coding variants (p.R47H, p.R62H, p.D87N, p.E151K, p.W191X, and p.L211P) for case-control analyses in a total of 906 LOAD cases vs. 2,487 controls. We identified significant LOAD risk association with p.L211P (p=0.01, OR=1.27, 95%CI=1.05-1.54) and suggestive association with p.W191X (p=0.08, OR=1.35, 95%CI=0.97-1.87). Conditional analysis suggests that p.L211P, which is in linkage disequilibrium with p.W191X, may be the stronger variant of the two, but does not rule out independent contribution of the latter. TREM2 p.L211P resides within the cytoplasmic domain and p.W191X is a stop-gain mutation within the shorter TREM-2V transcript. The coding variants within the extracellular domain of TREM2 previously shown to confer LOAD risk in Caucasians were extremely rare in our AA cohort and did not associate with LOAD risk. Our findings suggest that TREM2 coding variants also confer LOAD risk in AA, but implicate variants within different regions of the gene than those identified for Caucasian subjects. These results underscore the importance of investigating different ethnic populations for disease risk variant discovery, which may uncover allelic heterogeneity with potentially diverse mechanisms of action.

What factors influence uptake of retinal screening among young adults with type 2 diabetes? A qualitative study informed by the theoretical domains framework.

PubMed

Lake, Amelia J; Browne, Jessica L; Rees, Gwyneth; Speight, Jane

2017-06-01

Young adults with type 2 diabetes (T2D, 18-39years) face increased risk of vision loss from diabetic retinopathy (DR). Retinal screening is essential to detect DR, yet screening rates for this group are low and little is known about the underlying factors influencing this important behavior. Using the theoretical domains framework (TDF) to guide data collection and analysis, we explored screening barriers and facilitator, contrasting them with a comparator group of older adults with T2D (40+ years). Thirty semi-structured telephone interviews (10 younger, 20 older adults) were conducted. Data were coded into TDF domains with salience identified by "frequency" of reference. Screening facilitators and barriers were systematically compared between groups. Although many screening facilitators and barriers were shared by younger and older adults, additional factors highly relevant to the former included: social comparison with others ('social influences'); concern for the impact on the family unit, unrealistic optimism and perceived invulnerability ('beliefs about consequences'); lack of time and financial resources ('environmental context and resources'), and DR misconceptions ('knowledge'). This study demonstrated that young adult retinal screening behavior was influenced by additional social cognitive factors compared to older adults, providing a first-step evidence base for clinicians and other health professionals, and potential targets for future eye health and retinal screening interventions. Copyright © 2017 Elsevier Inc. All rights reserved.

Microsecond molecular dynamics simulations provide insight into the ATP-competitive inhibitor-induced allosteric protection of Akt kinase phosphorylation.

PubMed

Mou, Linkai; Cui, Tongwei; Liu, Weiguang; Zhang, Hong; Cai, Zhanxiu; Lu, Shaoyong; Gao, Guojun

2017-05-01

Akt is a serine/threonine protein kinase, a critical mediator of growth factor-induced survival in key cellular pathways. Allosteric signaling between protein intramolecular domains requires long-range communication mediated by hotspot residues, often triggered by ligand binding. Here, based on extensive 3 μs explicit solvent molecular dynamics (MD) simulations of Akt1 kinase domain in the unbound (apo) and ATP-competitive inhibitor, GDC-0068-bound states, we propose a molecular mechanism for allosteric regulation of Akt1 kinase phosphorylation by GDC-0068 binding to the ATP-binding site. MD simulations revealed that the apo Akt1 is flexible with two disengaged N- and C-lobes, equilibrated between the open and closed conformations. GDC-0068 occupancy of the ATP-binding site shifts the conformational equilibrium of Akt1 from the open conformation toward the closed conformation and stabilizes the closed state. This effect enables allosteric signal propagation from the GDC-0068 to the phosphorylated T308 (pT308) in the activation loop and restrains phosphatase access to pT308, thereby protecting the pT308 in the GDC-0068-bound Akt1. Importantly, functional hotspots involved in the allosteric communication from the GDC-0068 to the pT308 are identified. Our analysis of GDC-0068-induced allosteric protection of Akt kinase phosphorylation yields important new insights into the molecular mechanism of allosteric regulation of Akt kinase activity. © 2016 John Wiley & Sons A/S.

The Fortran-P Translator: Towards Automatic Translation of Fortran 77 Programs for Massively Parallel Processors

DOE PAGES

O'keefe, Matthew; Parr, Terence; Edgar, B. Kevin; ...

1995-01-01

Massively parallel processors (MPPs) hold the promise of extremely high performance that, if realized, could be used to study problems of unprecedented size and complexity. One of the primary stumbling blocks to this promise has been the lack of tools to translate application codes to MPP form. In this article we show how applications codes written in a subset of Fortran 77, called Fortran-P, can be translated to achieve good performance on several massively parallel machines. This subset can express codes that are self-similar, where the algorithm applied to the global data domain is also applied to each subdomain. Wemore » have found many codes that match the Fortran-P programming style and have converted them using our tools. We believe a self-similar coding style will accomplish what a vectorizable style has accomplished for vector machines by allowing the construction of robust, user-friendly, automatic translation systems that increase programmer productivity and generate fast, efficient code for MPPs.« less

Cluster analysis of quantitative MRI T2 and T1ρ relaxation times of cartilage identifies differences between healthy and ACL-injured individuals at 3T.

PubMed

Monu, U D; Jordan, C D; Samuelson, B L; Hargreaves, B A; Gold, G E; McWalter, E J

2017-04-01

To identify focal lesions of elevated MRI T 2 and T 1ρ relaxation times in articular cartilage of an ACL-injured group using a novel cluster analysis technique. Eighteen ACL-injured patients underwent 3T MRI T 2 and T 1ρ relaxometry at baseline, 6 months and 1 year and six healthy volunteers at baseline, 1 day and 1 year. Clusters of contiguous pixels above or below T 2 and T 1ρ intensity and area thresholds were identified on a projection map of the 3D femoral cartilage surface. The total area of femoral cartilage plate covered by clusters (%CA) was split into areas above (%CA+) and below (%CA-) the thresholds and the differences in %CA(+ or -) over time in the ACL-injured group were determined using the Wilcoxon signed rank test. %CA+ was greater in the ACL-injured patients than the healthy volunteers at 6 months and 1 year with average %CA+ of 5.2 ± 4.0% (p = 0.0054) and 6.6 ± 3.7% (p = 0.0041) for T 2 and 6.2 ± 7.1% (p = 0.063) and 8.2 ± 6.9% (p = 0.042) for T 1ρ , respectively. %CA- at 6 months and 1 year was 3.0 ± 1.8% (p > 0.1) and 5.9 ± 5.0% (p > 0.1) for T 2 and 4.4 ± 4.9% (p > 0.1) and 4.5 ± 4.6% (p > 0.1) for T 1ρ , respectively. With the proposed cluster analysis technique, we have quantified cartilage lesion coverage and demonstrated that the ACL-injured group had greater areas of elevated T 2 and T 1ρ relaxation times as compared to healthy volunteers. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Oral fluid and plasma 3,4-methylenedioxymethamphetamine (MDMA) and metabolite correlation after controlled oral MDMA administration.

PubMed

Desrosiers, Nathalie A; Barnes, Allan J; Hartman, Rebecca L; Scheidweiler, Karl B; Kolbrich-Spargo, Erin A; Gorelick, David A; Goodwin, Robert S; Huestis, Marilyn A

2013-05-01

Oral fluid (OF) offers a noninvasive sample collection for drug testing. However, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) in OF has not been adequately characterized in comparison to plasma. We administered oral low-dose (1.0 mg/kg) and high-dose (1.6 mg/kg) MDMA to 26 participants and collected simultaneous OF and plasma specimens for up to 143 h after dosing. We compared OF/plasma (OF/P) ratios, time of initial detection (t first), maximal concentrations (C max), time of peak concentrations (t max), time of last detection (t last), clearance, and 3,4-methylenedioxyamphetamine (MDA)-to-MDMA ratios over time. For OF MDMA and MDA, C max was higher, t last was later, and clearance was slower compared to plasma. For OF MDA only, t first was later compared to plasma. Median (range) OF/P ratios were 5.6 (0.1-52.3) for MDMA and 3.7 (0.7-24.3) for MDA. OF and plasma concentrations were weakly but significantly correlated (MDMA: R(2) = 0.438, MDA: R(2) = 0.197, p < 0.0001). Median OF/P ratios were significantly higher following high dose administration: MDMA low = 5.2 (0.1-40.4), high = 6.0 (0.4-52.3, p < 0.05); MDA low = 3.3 (0.7-17.1), high = 4.1 (0.9-24.3, p < 0.001). There was a large inter-subject variation in OF/P ratios. The MDA/MDMA ratios in plasma were higher than those in OF (p < 0.001), and the MDA/MDMA ratios significantly increased over time in OF and plasma. The MDMA and MDA concentrations were higher in OF than in plasma. OF and plasma concentrations were correlated, but large inter-subject variability precludes the estimation of plasma concentrations from OF.

Time Dependent Holographic Interferometry and Finite-Element Analysis of Heat Transfer Within a Rectangular Enclosure

DTIC Science & Technology

1976-09-01

describing the system are correctly assembled, a library subroutine (LEQT2F) functioning as a linear equation solver is called and the desired nodal... mooc ^30 •»-< * #00 + O00ɜ-tH Q(M I > •.-4(M-M- +30 ^f0*O I >o • -t-W-QOO 30 t^*Q(Mw O tO^ I o«o»-< •^ + 00 I fH (M(M3 -*>* (M +«o o fOOO *3Q • — » aoo...Documentation Center 2 Cameron Station Alexandria, Virginia 22314 Library , Code 0212 2 Naval Postgraduate School Monterey, California 93940 3

Human operator identification model and related computer programs

NASA Technical Reports Server (NTRS)

Kessler, K. M.; Mohr, J. N.

1978-01-01

Four computer programs which provide computational assistance in the analysis of man/machine systems are reported. The programs are: (1) Modified Transfer Function Program (TF); (2) Time Varying Response Program (TVSR); (3) Optimal Simulation Program (TVOPT); and (4) Linear Identification Program (SCIDNT). The TV program converts the time domain state variable system representative to frequency domain transfer function system representation. The TVSR program computes time histories of the input/output responses of the human operator model. The TVOPT program is an optimal simulation program and is similar to TVSR in that it produces time histories of system states associated with an operator in the loop system. The differences between the two programs are presented. The SCIDNT program is an open loop identification code which operates on the simulated data from TVOPT (or TVSR) or real operator data from motion simulators.

The critical role of p16/Rb pathway in the inhibition of GH3 cell cycle induced by T-2 toxin.

PubMed

Fatima, Zainab; Guo, Pu; Huang, Deyu; Lu, Qirong; Wu, Qinghua; Dai, Menghong; Cheng, Guyue; Peng, Dapeng; Tao, Yanfei; Ayub, Muhammad; Ul Qamar, Muhammad Tahir; Ali, Muhammad Waqar; Wang, Xu; Yuan, Zonghui

2018-05-01

T-2 toxin is a worldwide trichothecenetoxin and can cause various toxicities.T-2 toxin is involved in G1 phase arrest in several cell lines but molecular mechanism is still not clear. In present study, we used rat pituitary GH3 cells to investigate the mechanism involved in cell cycle arrest against T-2 toxin (40 nM) for 12, 24, 36 and 48 h as compared to control cells. GH3 cells showed a considerable increase in reactive oxygen species (ROS) as well as loss in mitochondrial membrane potential (△Ym) upon exposure to the T-2 toxin. Flow cytometry showed a significant time-dependent increase in percentage of apoptotic cells and gel electrophoresis showed the hallmark of apoptosis oligonucleosomal DNA fragmentation. Additionally, T-2 toxin-induced oxidative stress and DNA damage with a time-dependent significant increased expression of p53 favors the apoptotic process by the activation of caspase-3 in T-2 toxin treated cells. Cell cycle analysis by flow cytometry revealed a time-dependent increase ofG1 cell population along with the significant time-dependent up-regulation of mRNA and protein expression of p16 and p21 and significant down-regulation of cyclin D1, CDK4, and p-RB levels further verify the G1 phase arrest in GH3 cells. Morphology of GH3 cells by TEM clearly showed the damage and dysfunction to mitochondria and the cell nucleus. These findings for the first time demonstrate that T-2 toxin induces G1 phase cell cycle arrest by the involvement of p16/Rb pathway, along with ROS mediated oxidative stress and DNA damage with p53 and caspase cascade interaction, resulting in apoptosis in GH3 cells. Copyright © 2018 Elsevier B.V. All rights reserved.

Checking Equivalence of SPMD Programs Using Non-Interference

DTIC Science & Technology

2010-01-29

with it hopes to go beyond the limits of Moore’s law, but also worries that programming will become harder [5]. One of the reasons why parallel...array name in G or L, and e is an arithmetic expression of integer type. In the CUDA code shown in Section 3, b and t are represented by coreId and...b+ t. A second, optimized version of the program (using function “reverse2”, see Section 3) can be modeled as a tuple P2 = ( G ,L2, F 2), with G same

EEG error potentials detection and classification using time-frequency features for robot reinforcement learning.

PubMed

Boubchir, Larbi; Touati, Youcef; Daachi, Boubaker; Chérif, Arab Ali

2015-08-01

In thought-based steering of robots, error potentials (ErrP) can appear when the action resulting from the brain-machine interface (BMI) classifier/controller does not correspond to the user's thought. Using the Steady State Visual Evoked Potentials (SSVEP) techniques, ErrP, which appear when a classification error occurs, are not easily recognizable by only examining the temporal or frequency characteristics of EEG signals. A supplementary classification process is therefore needed to identify them in order to stop the course of the action and back up to a recovery state. This paper presents a set of time-frequency (t-f) features for the detection and classification of EEG ErrP in extra-brain activities due to misclassification observed by a user exploiting non-invasive BMI and robot control in the task space. The proposed features are able to characterize and detect ErrP activities in the t-f domain. These features are derived from the information embedded in the t-f representation of EEG signals, and include the Instantaneous Frequency (IF), t-f information complexity, SVD information, energy concentration and sub-bands' energies. The experiment results on real EEG data show that the use of the proposed t-f features for detecting and classifying EEG ErrP achieved an overall classification accuracy up to 97% for 50 EEG segments using 2-class SVM classifier.

Tetrahymena thermophila acidic ribosomal protein L37 contains an archaebacterial type of C-terminus.

PubMed

Hansen, T S; Andreasen, P H; Dreisig, H; Højrup, P; Nielsen, H; Engberg, J; Kristiansen, K

1991-09-15

We have cloned and characterized a Tetrahymena thermophila macronuclear gene (L37) encoding the acidic ribosomal protein (A-protein) L37. The gene contains a single intron located in the 3'-part of the coding region. Two major and three minor transcription start points (tsp) were mapped 39 to 63 nucleotides upstream from the translational start codon. The uppermost tsp mapped to the first T in a putative T. thermophila RNA polymerase II initiator element, TATAA. The coding region of L37 predicts a protein of 109 amino acid (aa) residues. A substantial part of the deduced aa sequence was verified by protein sequencing. The T. thermophila L37 clearly belongs to the P1-type family of eukaryotic A-proteins, but the C-terminal region has the hallmarks of archaebacterial A-proteins.

The complete mitochondrial genome of Pomacea canaliculata (Gastropoda: Ampullariidae).

PubMed

Zhou, Xuming; Chen, Yu; Zhu, Shanliang; Xu, Haigen; Liu, Yan; Chen, Lian

2016-01-01

The mitochondrial genome of Pomacea canaliculata (Gastropoda: Ampullariidae) is the first complete mtDNA sequence reported in the genus Pomacea. The total length of mtDNA is 15,707 bp, which containing 13 protein-coding genes, 2 ribosomal RNAs, 22 transfer RNAs, and a 359 bp non-coding region. The A + T content of the overall base composition of H-strand is 71.7% (T: 41%, C: 12.7%, A: 30.7%, G: 15.6%). ATP6, ATP8, CO1, CO2, ND1-3, ND5, ND6, ND4L and Cyt b genes begin with ATG as start codon, CO3 and ND4 begin with ATA. ATP8, CO2-3, ND4L, ND2-6 and Cyt b genes are terminated with TAA as stop codon, ATP6, ND1, and CO1 end with TAG. A long non-coding region is found and a 23 bp repeat unit repeat 11 times in this region.

On origin of genetic code and tRNA before translation

PubMed Central

2011-01-01

Background Synthesis of proteins is based on the genetic code - a nearly universal assignment of codons to amino acids (aas). A major challenge to the understanding of the origins of this assignment is the archetypal "key-lock vs. frozen accident" dilemma. Here we re-examine this dilemma in light of 1) the fundamental veto on "foresight evolution", 2) modular structures of tRNAs and aminoacyl-tRNA synthetases, and 3) the updated library of aa-binding sites in RNA aptamers successfully selected in vitro for eight amino acids. Results The aa-binding sites of arginine, isoleucine and tyrosine contain both their cognate triplets, anticodons and codons. We have noticed that these cases might be associated with palindrome-dinucleotides. For example, one-base shift to the left brings arginine codons CGN, with CG at 1-2 positions, to the respective anticodons NCG, with CG at 2-3 positions. Formally, the concomitant presence of codons and anticodons is also expected in the reverse situation, with codons containing palindrome-dinucleotides at their 2-3 positions, and anticodons exhibiting them at 1-2 positions. A closer analysis reveals that, surprisingly, RNA binding sites for Arg, Ile and Tyr "prefer" (exactly as in the actual genetic code) the anticodon(2-3)/codon(1-2) tetramers to their anticodon(1-2)/codon(2-3) counterparts, despite the seemingly perfect symmetry of the latter. However, since in vitro selection of aa-specific RNA aptamers apparently had nothing to do with translation, this striking preference provides a new strong support to the notion of the genetic code emerging before translation, in response to catalytic (and possibly other) needs of ancient RNA life. Consistently with the pre-translation origin of the code, we propose here a new model of tRNA origin by the gradual, Fibonacci process-like, elongation of a tRNA molecule from a primordial coding triplet and 5'DCCA3' quadruplet (D is a base-determinator) to the eventual 76 base-long cloverleaf-shaped molecule. Conclusion Taken together, our findings necessarily imply that primordial tRNAs, tRNA aminoacylating ribozymes, and (later) the translation machinery in general have been co-evolving to ''fit'' the (likely already defined) genetic code, rather than the opposite way around. Coding triplets in this primal pre-translational code were likely similar to the anticodons, with second and third nucleotides being more important than the less specific first one. Later, when the code was expanding in co-evolution with the translation apparatus, the importance of 2-3 nucleotides of coding triplets "transferred" to the 1-2 nucleotides of their complements, thus distinguishing anticodons from codons. This evolutionary primacy of anticodons in genetic coding makes the hypothesis of primal stereo-chemical affinity between amino acids and cognate triplets, the hypothesis of coding coenzyme handles for amino acids, the hypothesis of tRNA-like genomic 3' tags suggesting that tRNAs originated in replication, and the hypothesis of ancient ribozymes-mediated operational code of tRNA aminoacylation not mutually contradicting but rather co-existing in harmony. Reviewers This article was reviewed by Eugene V. Koonin, Wentao Ma (nominated by Juergen Brosius) and Anthony Poole. PMID:21342520

BIN1/M-Amphiphysin2 induces clustering of phosphoinositides to recruit its downstream partner dynamin

NASA Astrophysics Data System (ADS)

Picas, Laura; Viaud, Julien; Schauer, Kristine; Vanni, Stefano; Hnia, Karim; Fraisier, Vincent; Roux, Aurélien; Bassereau, Patricia; Gaits-Iacovoni, Frédérique; Payrastre, Bernard; Laporte, Jocelyn; Manneville, Jean-Baptiste; Goud, Bruno

2014-12-01

Phosphoinositides play a central role in many physiological processes by assisting the recruitment of proteins to membranes through specific phosphoinositide-binding motifs. How this recruitment is coordinated in space and time is not well understood. Here we show that BIN1/M-Amphiphysin2, a protein involved in T-tubule biogenesis in muscle cells and frequently mutated in centronuclear myopathies, clusters PtdIns(4,5)P2 to recruit its downstream partner dynamin. By using several mutants associated with centronuclear myopathies, we find that the N-BAR and the SH3 domains of BIN1 control the kinetics and the accumulation of dynamin on membranes, respectively. We show that phosphoinositide clustering is a mechanism shared by other proteins that interact with PtdIns(4,5)P2, but do not contain a BAR domain. Our numerical simulations point out that clustering is a diffusion-driven process in which phosphoinositide molecules are not sequestered. We propose that this mechanism plays a key role in the recruitment of downstream phosphoinositide-binding proteins.

Crystal structure of Cex1p reveals the mechanism of tRNA trafficking between nucleus and cytoplasm.

PubMed

Nozawa, Kayo; Ishitani, Ryuichiro; Yoshihisa, Tohru; Sato, Mamoru; Arisaka, Fumio; Kanamaru, Shuji; Dohmae, Naoshi; Mangroo, Dev; Senger, Bruno; Becker, Hubert D; Nureki, Osamu

2013-04-01

In all eukaryotes, transcribed precursor tRNAs are maturated by processing and modification processes in nucleus and are transported to the cytoplasm. The cytoplasmic export protein (Cex1p) captures mature tRNAs from the nuclear export receptor (Los1p) on the cytoplasmic side of the nuclear pore complex, and it delivers them to eukaryotic elongation factor 1α. This conserved Cex1p function is essential for the quality control of mature tRNAs to ensure accurate translation. However, the structural basis of how Cex1p recognizes tRNAs and shuttles them to the translational apparatus remains unclear. Here, we solved the 2.2 Å resolution crystal structure of Saccharomyces cerevisiae Cex1p with C-terminal 197 disordered residues truncated. Cex1p adopts an elongated architecture, consisting of N-terminal kinase-like and a C-terminal α-helical HEAT repeat domains. Structure-based biochemical analyses suggested that Cex1p binds tRNAs on its inner side, using the positively charged HEAT repeat surface and the C-terminal disordered region. The N-terminal kinase-like domain acts as a scaffold to interact with the Ran-exportin (Los1p·Gsp1p) machinery. These results provide the structural basis of Los1p·Gsp1p·Cex1p·tRNA complex formation, thus clarifying the dynamic mechanism of tRNA shuttling from exportin to the translational apparatus.

Development of Simulated Directional Audio for Cockpit Applications

DTIC Science & Technology

1986-01-01

011 ’rhoodore JT.. (2erth, Jeffrev M.. Enpolivinnn.,Will1am R. and Folds, Deennis J. 12a. T’fP6 OP REPORT I131. TIME QW1COVEREDT’PRPOT(r. oDO 5 AG ON...of the aludio si~nal, in the time and frequency domains, which enhance localization performance with simulated cues. Previous research is reviewed...dichotically. Localization accuracy and response time were compared for: (1) nine different filtered noise stimuli, designed to make available some

Application of LEED (trademark) and SPiRiT to a Proposed Building Design

DTIC Science & Technology

2003-03-01

TOTAL AREA S CAT ARLOC INSTALLATION NO CODE C QTY UM OCPD F CODE 1) 24004 Aberdeen Provi E1890...ARLOC INSTALLATION NO CODE C QTY UM OCPD F CODE 1) 24004 Aberdeen Provi E3832 31010 P 13,000 SF 13,000 R

Myosin 3A Kinase Activity Is Regulated by Phosphorylation of the Kinase Domain Activation Loop*

PubMed Central

Quintero, Omar A.; Unrath, William C.; Stevens, Stanley M.; Manor, Uri; Kachar, Bechara; Yengo, Christopher M.

2013-01-01

Class III myosins are unique members of the myosin superfamily in that they contain both a motor and kinase domain. We have found that motor activity is decreased by autophosphorylation, although little is known about the regulation of the kinase domain. We demonstrate by mass spectrometry that Thr-178 and Thr-184 in the kinase domain activation loop and two threonines in the loop 2 region of the motor domain are autophosphorylated (Thr-908 and Thr-919). The kinase activity of MYO3A 2IQ with the phosphomimic (T184E) or phosphoblock (T184A) mutations demonstrates that kinase activity is reduced 30-fold as a result of the T184A mutation, although the Thr-178 site only had a minor impact on kinase activity. Interestingly, the actin-activated ATPase activity of MYO3A 2IQ is slightly reduced as a result of the T178A and T184A mutations suggesting coupling between motor and kinase domains. Full-length GFP-tagged T184A and T184E MYO3A constructs transfected into COS7 cells do not disrupt the ability of MYO3A to localize to filopodia structures. In addition, we demonstrate that T184E MYO3A reduces filopodia elongation in the presence of espin-1, whereas T184A enhances filopodia elongation in a similar fashion to kinase-dead MYO3A. Our results suggest that as MYO3A accumulates at the tips of actin protrusions, autophosphorylation of Thr-184 enhances kinase activity resulting in phosphorylation of the MYO3A motor and reducing motor activity. The differential regulation of the kinase and motor activities allows for MYO3A to precisely self-regulate its concentration in the actin bundle-based structures of cells. PMID:24214986

Myosin 3A kinase activity is regulated by phosphorylation of the kinase domain activation loop.

PubMed

Quintero, Omar A; Unrath, William C; Stevens, Stanley M; Manor, Uri; Kachar, Bechara; Yengo, Christopher M

2013-12-27

Class III myosins are unique members of the myosin superfamily in that they contain both a motor and kinase domain. We have found that motor activity is decreased by autophosphorylation, although little is known about the regulation of the kinase domain. We demonstrate by mass spectrometry that Thr-178 and Thr-184 in the kinase domain activation loop and two threonines in the loop 2 region of the motor domain are autophosphorylated (Thr-908 and Thr-919). The kinase activity of MYO3A 2IQ with the phosphomimic (T184E) or phosphoblock (T184A) mutations demonstrates that kinase activity is reduced 30-fold as a result of the T184A mutation, although the Thr-178 site only had a minor impact on kinase activity. Interestingly, the actin-activated ATPase activity of MYO3A 2IQ is slightly reduced as a result of the T178A and T184A mutations suggesting coupling between motor and kinase domains. Full-length GFP-tagged T184A and T184E MYO3A constructs transfected into COS7 cells do not disrupt the ability of MYO3A to localize to filopodia structures. In addition, we demonstrate that T184E MYO3A reduces filopodia elongation in the presence of espin-1, whereas T184A enhances filopodia elongation in a similar fashion to kinase-dead MYO3A. Our results suggest that as MYO3A accumulates at the tips of actin protrusions, autophosphorylation of Thr-184 enhances kinase activity resulting in phosphorylation of the MYO3A motor and reducing motor activity. The differential regulation of the kinase and motor activities allows for MYO3A to precisely self-regulate its concentration in the actin bundle-based structures of cells.

Right- and left-handed three-helix proteins. II. Similarity and differences in mechanical unfolding of proteins.

PubMed

Glyakina, Anna V; Likhachev, Ilya V; Balabaev, Nikolay K; Galzitskaya, Oxana V

2014-01-01

Here, we study mechanical properties of eight 3-helix proteins (four right-handed and four left-handed ones), which are similar in size under stretching at a constant speed and at a constant force on the atomic level using molecular dynamics simulations. The analysis of 256 trajectories from molecular dynamics simulations with explicit water showed that the right-handed three-helix domains are more mechanically resistant than the left-handed domains. Such results are observed at different extension velocities studied (192 trajectories obtained at the following conditions: v = 0.1, 0.05, and 0.01 Å ps(-1) , T = 300 K) and under constant stretching force (64 trajectories, F = 800 pN, T = 300 K). We can explain this by the fact, at least in part, that the right-handed domains have a larger number of contacts per residue and the radius of cross section than the left-handed domains. Copyright © 2013 Wiley Periodicals, Inc.

PG1058 Is a Novel Multidomain Protein Component of the Bacterial Type IX Secretion System

PubMed Central

Veith, Paul D.; Butler, Catherine A.; Nor Muhammad, Nor A.; Chen, Yu-Yen; Slakeski, Nada; Peng, Benjamin; Zhang, Lianyi; Dashper, Stuart G.; Cross, Keith J.; Cleal, Steven M.; Moore, Caroline; Reynolds, Eric C.

2016-01-01

Porphyromonas gingivalis utilises the Bacteroidetes-specific type IX secretion system (T9SS) to export proteins across the outer membrane (OM), including virulence factors such as the gingipains. The secreted proteins have a conserved carboxy-terminal domain essential for type IX secretion that is cleaved upon export. In P. gingivalis the T9SS substrates undergo glycosylation with anionic lipopolysaccharide (A-LPS) and are attached to the OM. In this study, comparative analyses of 24 Bacteroidetes genomes identified ten putative novel components of the T9SS in P. gingivalis, one of which was PG1058. Computer modelling of the PG1058 structure predicted a novel N- to C-terminal architecture comprising a tetratricopeptide repeat (TPR) domain, a β-propeller domain, a carboxypeptidase regulatory domain-like fold (CRD) and an OmpA_C-like putative peptidoglycan binding domain. Inactivation of pg1058 in P. gingivalis resulted in loss of both colonial pigmentation and surface-associated proteolytic activity; a phenotype common to T9SS mutants. Immunoblot and LC-MS/MS analyses of subcellular fractions revealed T9SS substrates accumulated within the pg1058 mutant periplasm whilst whole-cell ELISA showed the Kgp gingipain was absent from the cell surface, confirming perturbed T9SS function. Immunoblot, TEM and whole-cell ELISA analyses indicated A-LPS was produced and present on the pg1058 mutant cell surface although it was not linked to T9SS substrate proteins. This indicated that PG1058 is crucial for export of T9SS substrates but not for the translocation of A-LPS. PG1058 is a predicted lipoprotein and was localised to the periplasmic side of the OM using whole-cell ELISA, immunoblot and LC-MS/MS analyses of subcellular fractions. The structural prediction and localisation of PG1058 suggests that it may have a role as an essential scaffold linking the periplasmic and OM components of the T9SS. PMID:27711252

Interaction of multiferroic properties and interfaces in hexagonal LuMnO3 ceramics

NASA Astrophysics Data System (ADS)

Baghizadeh, A.; Vieira, J. M.; Stroppa, D. G.; Mirzadeh Vaghefi, P.; Graça, M. P.; Amaral, J. S.; Willinger, M.-G.; Amaral, V. S.

2017-02-01

A study on the underlying interaction mechanisms between lattice constants, magnetic and dielectric properties with inhomogeneities or internal interfaces in hexagonal, off-stoichiometric LuMnO3 oxide is presented. By increasing Mn content the a-axis constant and volume of the unit cell, the antiferromagnetic (AFM) Néel temperature, T N, and frustration factor of the frustrated Mn3+ trimmers in basal plane show decreasing trends. It was found that increasing the annealing time improves the properties of the lattices and progressively eliminates secondary phases for compositions within the solid solution stability limits. A magnetic contribution below T N is observed for all samples. Two regimes of magnetization below and above 45 K were observed in the AFM state. The magnetic contribution below T N is assigned to either the secondary phase or internal interfaces like ferroelectric (FE) domain walls. Magneto-dielectric coupling at T N is preserved in off-stoichiometric ceramics. The presence of a low temperature anomaly of the dielectric constant is correlated to the composition of the solid solution in off-stoichiometric ceramics. Large FE domains are observed in piezoresponse force microscopy (PFM) images of doped and un-doped ceramics, whereas atomic structure analysis indicates the parallel formation of nano-sized FE domains. A combination of measured properties and microscopy images of micron- and nano-sized domains ascertain the role of lattice distortion and stability of solid solution on multiferroic properties.

Molecular cloning and analysis of Schizosaccharomyces pombe Reb1p: sequence-specific recognition of two sites in the far upstream rDNA intergenic spacer.

PubMed Central

Zhao, A; Guo, A; Liu, Z; Pape, L

1997-01-01

The coding sequences for a Schizosaccharomyces pombe sequence-specific DNA binding protein, Reb1p, have been cloned. The predicted S. pombe Reb1p is 24-29% identical to mouse TTF-1 (transcription termination factor-1) and Saccharomyces cerevisiae REB1 protein, both of which direct termination of RNA polymerase I catalyzed transcripts. The S.pombe Reb1 cDNA encodes a predicted polypeptide of 504 amino acids with a predicted molecular weight of 58.4 kDa. The S. pombe Reb1p is unusual in that the bipartite DNA binding motif identified originally in S.cerevisiae and Klyveromyces lactis REB1 proteins is uninterrupted and thus S.pombe Reb1p may contain the smallest natural REB1 homologous DNA binding domain. Its genomic coding sequences were shown to be interrupted by two introns. A recombinant histidine-tagged Reb1 protein bearing the rDNA binding domain has two homologous, sequence-specific binding sites in the S. pomber DNA intergenic spacer, located between 289 and 480 nt downstream of the end of the approximately 25S rRNA coding sequences. Each binding site is 13-14 bp downstream of two of the three proposed in vivo termination sites. The core of this 17 bp site, AGGTAAGGGTAATGCAC, is specifically protected by Reb1p in footprinting analysis. PMID:9016645

Crystal Structures and Thermodynamic Analysis Reveal Distinct Mechanisms of CD28 Phosphopeptide Binding to the Src Homology 2 (SH2) Domains of Three Adaptor Proteins*

PubMed Central

Inaba, Satomi; Numoto, Nobutaka; Ogawa, Shuhei; Morii, Hisayuki; Ikura, Teikichi; Abe, Ryo; Ito, Nobutoshi; Oda, Masayuki

2017-01-01

Full activation of T cells and differentiation into effector T cells are essential for many immune responses and require co-stimulatory signaling via the CD28 receptor. Extracellular ligand binding to CD28 recruits protein-tyrosine kinases to its cytoplasmic tail, which contains a YMNM motif. Following phosphorylation of the tyrosine, the proteins growth factor receptor-bound protein 2 (Grb2), Grb2-related adaptor downstream of Shc (Gads), and p85 subunit of phosphoinositide 3-kinase may bind to pYMNM (where pY is phosphotyrosine) via their Src homology 2 (SH2) domains, leading to downstream signaling to distinct immune pathways. These three adaptor proteins bind to the same site on CD28 with variable affinity, and all are important for CD28-mediated co-stimulatory function. However, the mechanism of how these proteins recognize and compete for CD28 is unclear. To visualize their interactions with CD28, we have determined the crystal structures of Gads SH2 and two p85 SH2 domains in complex with a CD28-derived phosphopeptide. The high resolution structures obtained revealed that, whereas the CD28 phosphopeptide bound to Gads SH2 is in a bent conformation similar to that when bound to Grb2 SH2, it adopts a more extended conformation when bound to the N- and C-terminal SH2 domains of p85. These differences observed in the peptide-protein interactions correlated well with the affinity and other thermodynamic parameters for each interaction determined by isothermal titration calorimetry. The detailed insight into these interactions reported here may inform the development of compounds that specifically inhibit the association of CD28 with these adaptor proteins to suppress excessive T cell responses, such as in allergies and autoimmune diseases. PMID:27927989

Crystal Structures and Thermodynamic Analysis Reveal Distinct Mechanisms of CD28 Phosphopeptide Binding to the Src Homology 2 (SH2) Domains of Three Adaptor Proteins.

PubMed

Inaba, Satomi; Numoto, Nobutaka; Ogawa, Shuhei; Morii, Hisayuki; Ikura, Teikichi; Abe, Ryo; Ito, Nobutoshi; Oda, Masayuki

2017-01-20

Full activation of T cells and differentiation into effector T cells are essential for many immune responses and require co-stimulatory signaling via the CD28 receptor. Extracellular ligand binding to CD28 recruits protein-tyrosine kinases to its cytoplasmic tail, which contains a YMNM motif. Following phosphorylation of the tyrosine, the proteins growth factor receptor-bound protein 2 (Grb2), Grb2-related adaptor downstream of Shc (Gads), and p85 subunit of phosphoinositide 3-kinase may bind to pYMNM (where pY is phosphotyrosine) via their Src homology 2 (SH2) domains, leading to downstream signaling to distinct immune pathways. These three adaptor proteins bind to the same site on CD28 with variable affinity, and all are important for CD28-mediated co-stimulatory function. However, the mechanism of how these proteins recognize and compete for CD28 is unclear. To visualize their interactions with CD28, we have determined the crystal structures of Gads SH2 and two p85 SH2 domains in complex with a CD28-derived phosphopeptide. The high resolution structures obtained revealed that, whereas the CD28 phosphopeptide bound to Gads SH2 is in a bent conformation similar to that when bound to Grb2 SH2, it adopts a more extended conformation when bound to the N- and C-terminal SH2 domains of p85. These differences observed in the peptide-protein interactions correlated well with the affinity and other thermodynamic parameters for each interaction determined by isothermal titration calorimetry. The detailed insight into these interactions reported here may inform the development of compounds that specifically inhibit the association of CD28 with these adaptor proteins to suppress excessive T cell responses, such as in allergies and autoimmune diseases. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Two-Dimensional Ffowcs Williams/Hawkings Equation Solver

NASA Technical Reports Server (NTRS)

Lockard, David P.

2005-01-01

FWH2D is a Fortran 90 computer program that solves a two-dimensional (2D) version of the equation, derived by J. E. Ffowcs Williams and D. L. Hawkings, for sound generated by turbulent flow. FWH2D was developed especially for estimating noise generated by airflows around such approximately 2D airframe components as slats. The user provides input data on fluctuations of pressure, density, and velocity on some surface. These data are combined with information about the geometry of the surface to calculate histories of thickness and loading terms. These histories are fast-Fourier-transformed into the frequency domain. For each frequency of interest and each observer position specified by the user, kernel functions are integrated over the surface by use of the trapezoidal rule to calculate a pressure signal. The resulting frequency-domain signals are inverse-fast-Fourier-transformed back into the time domain. The output of the code consists of the time- and frequency-domain representations of the pressure signals at the observer positions. Because of its approximate nature, FWH2D overpredicts the noise from a finite-length (3D) component. The advantage of FWH2D is that it requires a fraction of the computation time of a 3D Ffowcs Williams/Hawkings solver.

Multigrid direct numerical simulation of the whole process of flow transition in 3-D boundary layers

NASA Technical Reports Server (NTRS)

Liu, Chaoqun; Liu, Zhining

1993-01-01

A new technology was developed in this study which provides a successful numerical simulation of the whole process of flow transition in 3-D boundary layers, including linear growth, secondary instability, breakdown, and transition at relatively low CPU cost. Most other spatial numerical simulations require high CPU cost and blow up at the stage of flow breakdown. A fourth-order finite difference scheme on stretched and staggered grids, a fully implicit time marching technique, a semi-coarsening multigrid based on the so-called approximate line-box relaxation, and a buffer domain for the outflow boundary conditions were all used for high-order accuracy, good stability, and fast convergence. A new fine-coarse-fine grid mapping technique was developed to keep the code running after the laminar flow breaks down. The computational results are in good agreement with linear stability theory, secondary instability theory, and some experiments. The cost for a typical case with 162 x 34 x 34 grid is around 2 CRAY-YMP CPU hours for 10 T-S periods.

Development of an Aeroelastic Analysis Including a Viscous Flow Model

NASA Technical Reports Server (NTRS)

Keith, Theo G., Jr.; Bakhle, Milind A.

2001-01-01

Under this grant, Version 4 of the three-dimensional Navier-Stokes aeroelastic code (TURBO-AE) has been developed and verified. The TURBO-AE Version 4 aeroelastic code allows flutter calculations for a fan, compressor, or turbine blade row. This code models a vibrating three-dimensional bladed disk configuration and the associated unsteady flow (including shocks, and viscous effects) to calculate the aeroelastic instability using a work-per-cycle approach. Phase-lagged (time-shift) periodic boundary conditions are used to model the phase lag between adjacent vibrating blades. The direct-store approach is used for this purpose to reduce the computational domain to a single interblade passage. A disk storage option, implemented using direct access files, is available to reduce the large memory requirements of the direct-store approach. Other researchers have implemented 3D inlet/exit boundary conditions based on eigen-analysis. Appendix A: Aeroelastic calculations based on three-dimensional euler analysis. Appendix B: Unsteady aerodynamic modeling of blade vibration using the turbo-V3.1 code.

The socializing effect of classroom aggression on the development of aggression and social rejection: A two-wave multilevel analysis.

PubMed

Rohlf, Helena; Krahé, Barbara; Busching, Robert

2016-10-01

The current study examined the moderating effect of classroom aggression on the development of individual aggression and on the path from individual aggression to social rejection over time. The study included 1,284 elementary school children and consisted of two data waves 10months apart. At both time points, teachers assessed the children's physical and relational aggression and their social rejection status. Multi-level analyses revealed that the classroom level of relational aggression moderated the link between individual relational aggression at T1 and T2 (b=-0.18, 95% CI [-0.32, -0.05], p<.01) and the link between T1 relational aggression and T2 social rejection (b=-0.12, 95% CI [-0.23, -0.003], p<.01). Being in a classroom where relational aggression was prevalent increased relational aggression among children with a low level of relational aggression at T1. Furthermore, a high individual level of relational aggression predicted greater social rejection in classrooms with a low level of relational aggression. Children were mainly influenced by their same-gender peers. Boys as a group had a greater influence than girls on their peers of either gender in the domain of relational aggression, whereas girls as a group had a greater influence in the domain of physical aggression. The contributions of analyzing cross-level interaction to understanding the developmental patterns of aggression and social rejection in middle childhood are discussed. Copyright © 2016 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

Disease-Homologous Mutation in the Cation Diffusion Facilitator Protein MamM Causes Single-Domain Structural Loss and Signifies Its Importance

PubMed Central

Barber-Zucker, Shiran; Uebe, René; Davidov, Geula; Navon, Yotam; Sherf, Dror; Chill, Jordan H.; Kass, Itamar; Bitton, Ronit; Schüler, Dirk; Zarivach, Raz

2016-01-01

Cation diffusion facilitators (CDF) are highly conserved, metal ion efflux transporters that maintain divalent transition metal cation homeostasis. Most CDF proteins contain two domains, the cation transporting transmembrane domain and the regulatory cytoplasmic C-terminal domain (CTD). MamM is a magnetosome-associated CDF protein essential for the biomineralization of magnetic iron-oxide particles in magnetotactic bacteria. To investigate the structure-function relationship of CDF cytoplasmic domains, we characterized a MamM M250P mutation that is synonymous with the disease-related mutation L349P of the human CDF protein ZnT-10. Our results show that the M250P exchange in MamM causes severe structural changes in its CTD resulting in abnormal reduced function. Our in vivo, in vitro and in silico studies indicate that the CTD fold is critical for CDF proteins’ proper function and support the previously suggested role of the CDF cytoplasmic domain as a CDF regulatory element. Based on our results, we also suggest a mechanism for the effects of the ZnT-10 L349P mutation in human. PMID:27550551

Towards Deciphering the Hidden Mechanisms That Contribute to the Antigenic Activation Process of Human Vγ9Vδ2 T Cells.

PubMed

Boutin, Lola; Scotet, Emmanuel

2018-01-01

Vγ9Vδ2 T cells represent a major unconventional γδ T cell subset located in the peripheral blood of adults in humans and several non-human primates. Lymphocytes that constitute this transitional subset can sense subtle level changes of intracellular phosphorylated intermediates of the isoprenoid biosynthesis pathway (phosphoantigens, pAg), such as isopentenyl pyrophosphate, during cell stress events. This unique antigenic activation process operates in a rigorous framework that requires the expression of butyrophilin 3A1 (BTN3A1/CD277) molecules, which are type I glycoproteins that belong to the B7 family. Several studies have further shown that pAg specifically bind to the intracellular B30.2 domain of BTN3A1 linked to the antigenic activation of Vγ9Vδ2 T cells. Here, we highlight the recent advances in BTN3A1 dynamics induced upon the binding of pAg and the contribution of the different subunits to this activation process. Recent reports support that conformational modifications of BTN3A1 might represent a key step in the detection of infection or tumorigenesis by Vγ9Vδ2 T cells. A better understanding of this mechanism will help optimize novel immunotherapeutical approaches that target defined functions of this unique γδ T cell subset.