Science in a communist country: The case of the XXIInd International Congress of Psychology in Leipzig (1980).

PubMed

Schönpflug, Wolfgang; Lüer, Gerd

2013-05-01

The XXIInd International Congress of Psychology (ICP) in Leipzig in 1980 is a case that illustrates the mutual relationship between science and politics, specifically of the role of science in a communist state. We focus first on the situation of the discipline of psychology within the (East) German Democratic Republic (GDR). Second, we provide a detailed description of the interactions between the International Union of Psychological Science (IUPS) and the communist regime of the GDR. The Psychological Association of the GDR was commissioned by the IUPS to organize the congress. The Communist Party, being an omnipresent authority in the state, both supported and tried to manipulate the Leipzig conference for its political goals. Based on archival materials and on recent reports, we reconstruct three positions: From their ideological position, the GDR expected the conference to improve their standing in international politics and to serve as a platform for promoting communist doctrines; from a pragmatic position, the IUPS sought to guarantee free access to the conference and political neutrality of the scientific program; from a humanistic position, no support should be given to a totalitarian system accused of human rights violations. We compare the formal organization as implemented by the Communist Party for ideological purposes with the informal organizational structure, which operated toward pragmatic solutions. Finally, we discuss the compromises between the IUPS and the communist authorities. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

RNA-protein interactions in an unstructured context.

PubMed

Zagrovic, Bojan; Bartonek, Lukas; Polyansky, Anton A

2018-05-31

Despite their importance, our understanding of noncovalent RNA-protein interactions is incomplete. This especially concerns the binding between RNA and unstructured protein regions, a widespread class of such interactions. Here, we review the recent experimental and computational work on RNA-protein interactions in an unstructured context with a particular focus on how such interactions may be shaped by the intrinsic interaction affinities between individual nucleobases and protein side chains. Specifically, we articulate the claim that the universal genetic code reflects the binding specificity between nucleobases and protein side chains and that, in turn, the code may be seen as the Rosetta stone for understanding RNA-protein interactions in general. © 2018 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Protein-Water and Protein-Buffer Interactions in the Aqueous Solution of an Intrinsically Unstructured Plant Dehydrin: NMR Intensity and DSC Aspects

PubMed Central

Tompa, P.; Bánki, P.; Bokor, M.; Kamasa, P.; Kovács, D.; Lasanda, G.; Tompa, K.

2006-01-01

Proton NMR intensity and differential scanning calorimetry measurements were carried out on an intrinsically unstructured late embryogenesis abundant protein, ERD10, the globular BSA, and various buffer solutions to characterize water and ion binding of proteins by this novel combination of experimental approaches. By quantifying the number of hydration water molecules, the results demonstrate the interaction between the protein and NaCl and between buffer and NaCl on a microscopic level. The findings overall provide direct evidence that the intrinsically unstructured ERD10 not only has a high hydration capacity but can also bind a large amount of charged solute ions. In accord, the dehydration stress function of this protein probably results from its simultaneous action of retaining water in the drying cells and preventing an adverse increase in ionic strength, thus countering deleterious effects such as protein denaturation. PMID:16798808

Single-Molecule FRET Spectroscopy and the Polymer Physics of Unfolded and Intrinsically Disordered Proteins.

PubMed

Schuler, Benjamin; Soranno, Andrea; Hofmann, Hagen; Nettels, Daniel

2016-07-05

The properties of unfolded proteins have long been of interest because of their importance to the protein folding process. Recently, the surprising prevalence of unstructured regions or entirely disordered proteins under physiological conditions has led to the realization that such intrinsically disordered proteins can be functional even in the absence of a folded structure. However, owing to their broad conformational distributions, many of the properties of unstructured proteins are difficult to describe with the established concepts of structural biology. We have thus seen a reemergence of polymer physics as a versatile framework for understanding their structure and dynamics. An important driving force for these developments has been single-molecule spectroscopy, as it allows structural heterogeneity, intramolecular distance distributions, and dynamics to be quantified over a wide range of timescales and solution conditions. Polymer concepts provide an important basis for relating the physical properties of unstructured proteins to folding and function.

MECHANISM OF ALPHA-SYNUCLEIN OLIGOMERIZATION AND MEMBRANE INTERACTION: THEORETICAL APPROACH TO UNSTRUCTURED PROTEINS STUDIES

PubMed Central

Tsigelny, Igor F.; Sharikov, Yuriy; Miller, Mark A.; Masliah, Eliezer

2008-01-01

Misfolding and oligomerization of unstructured proteins is involved in the pathogenesis of Parkinson’s (PD), Alzheimer’s (AD), Huntington’s, and other neurodegenerative disorders. Elucidation of possible conformations of these proteins and their interactions with the membrane is necessary to understand the molecular mechanisms of neurodegeneration. We developed a strategy that makes it possible to elucidate the molecular mechanisms of of alpha-synuclein aggregation- a key molecular event in the pathogenesis of PD. This strategy can be also useful for the study of other unstructured proteins involved in neurodegeneration. The results of these theoretical studies have been confirmed with biochemical and electrophysiological studies. Our studies provide insights into the molecular mechanism for PD initiation and progression, and provide a useful paradigm for identifying possible therapeutic interventions through computational modeling. PMID:18640077

Recording of electrohysterogram laplacian potential.

PubMed

Alberola-Rubio, J; Garcia-Casado, J; Ye-Lin, Y; Prats-Boluda, G; Perales, A

2011-01-01

Preterm birth is the main cause of the neonatal morbidity. Noninvasive recording of uterine myoelectrical activity (electrohysterogram, EHG) could be an alternative to the monitoring of uterine dynamics which are currently based on tocodynamometers (TOCO). The analysis of uterine electromyogram characteristics could help the early diagnosis of preterm birth. Laplacian recordings of other bioelectrical signals have proved to enhance spatial selectivity and to reduce interferences in comparison to monopolar and bipolar surface recordings. The main objective of this paper is to check the feasibility of the noninvasive recording of uterine myoelectrical activity by means of laplacian techniques. Four bipolar EHG signals, discrete laplacian obtained from five monopolar electrodes and the signals picked up by two active concentric-ringed-electrodes were recorded on 5 women with spontaneous or induced labor. Intrauterine pressure (IUP) and TOCO were also simultaneously recorded. To evaluate the uterine contraction detectability of the different noninvasive methods in comparison to IUP the contractions consistency index (CCI) was calculated. Results show that TOCO is less consistent (83%) than most EHG bipolar recording channels (91%, 83%, 87%, and 76%) to detect the uterine contractions identified in IUP. Moreover laplacian EHG signals picked up by ringed-electrodes proved to be as consistent (91%) as the best bipolar recordings in addition to significantly reduce ECG interference.

Mother's prior intrauterine position affects the sex ratio of her offspring in house mice.

PubMed

Vandenbergh, J G; Huggett, C L

1994-11-08

Sex ratio alterations related to environmental factors occur in several mammals, but no mechanism has been identified to explain the adjustment. Intrauterine position (IUP) may provide the context in which such alterations occur. Previous studies on house mice and gerbils reveal that the position of a fetus in the uterus in relation to the sex of its neighbors influences its later anatomy, physiology, and behavior. The anogenital distance (AGD) of females located between two males (2M) is longer than that of females not between two males (OM). We have found that the IUP, as determined by cesarean section and by an index of the AGD, correlates with the sex ratio of the litters produced by female mice. The sex ratio of the first litter born to 2M females was 58% males, for 1M females was 51% males and for OM females was 42% males. The effect on sex ratio continues into the second litter. The number of pups produced by mothers of different IUPs in her first two litters did not differ, suggesting that the sex ratio adjustment occurs prior to parturition. These results provide a basis for the natural variability observed in sex ratios of litter-bearing mammals and suggest that one or more intrauterine mechanisms may be responsible for environmentally related sex ratio alterations.

40 CFR 35.3150 - Intended Use Plan (IUP).

Code of Federal Regulations, 2010 CFR

2010-07-01

... ASSISTANCE STATE AND LOCAL ASSISTANCE State Water Pollution Control Revolving Funds § 35.3150 Intended Use... State's water pollution control revolving fund. (3) Information on the SRF activities to be supported...

How and when human chorionic gonadotropin curves in women with an ectopic pregnancy mimic other outcomes: differences by race and ethnicity.

PubMed

Dillon, Katherine E; Sioulas, Vasileios D; Sammel, Mary D; Chung, Karine; Takacs, Peter; Shaunik, Alka; Barnhart, Kurt T

2012-10-01

To investigate the hCG profiles in a diverse patient group with ectopic pregnancy (EP) and to understand when they may mimic the curves of an intrauterine pregnancy (IUP) or spontaneous abortion (SAB). Retrospective cohort study. Three university hospitals. One hundred seventy-nine women with symptomatic pregnancy of unknown location. None. Slope of log hCG; days and visits to final diagnosis. Of women with an EP, 60% initially exhibited an increase in hCG values, with a median slope of 32% increase in 2 days; 40% of subjects initially had an hCG decrease, with the median slope calculated as a 15% decline in 2 days. In total, the hCG curves in 27% of women diagnosed with EP resembled that of a growing IUP or SAB. Of the EP hCG curves, 16% demonstrated a change in the direction of the slope of the curve. This was more common in African Americans and less evident in Hispanics. Furthermore, it was associated with more clinical visits and days until final diagnosis. The rate of change in serial hCG values can be used to distinguish EP from an IUP or SAB in only 73% of cases. The number of women who had a change in direction of serial hCG values was associated with race and ethnicity. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Peptide affinity analysis of proteins that bind to an unstructured NH2-terminal region of the osmoprotective transcription factor NFAT5

PubMed Central

DuMond, Jenna F.; Ramkissoon, Kevin; Zhang, Xue; Izumi, Yuichiro; Wang, Xujing; Eguchi, Koji; Gao, Shouguo; Mukoyama, Masashi; Ferraris, Joan D.

2016-01-01

NFAT5 is an osmoregulated transcription factor that particularly increases expression of genes involved in protection against hypertonicity. Transcription factors often contain unstructured regions that bind co-regulatory proteins that are crucial for their function. The NH2-terminal region of NFAT5 contains regions predicted to be intrinsically disordered. We used peptide aptamer-based affinity chromatography coupled with mass spectrometry to identify protein preys pulled down by one or more overlapping 20 amino acid peptide baits within a predicted NH2-terminal unstructured region of NFAT5. We identify a total of 467 unique protein preys that associate with at least one NH2-terminal peptide bait from NFAT5 in either cytoplasmic or nuclear extracts from HEK293 cells treated with elevated, normal, or reduced NaCl concentrations. Different sets of proteins are pulled down from nuclear vs. cytoplasmic extracts. We used GeneCards to ascertain known functions of the protein preys. The protein preys include many that were previously known, but also many novel ones. Consideration of the novel ones suggests many aspects of NFAT5 regulation, interaction and function that were not previously appreciated, for example, hypertonicity inhibits NFAT5 by sumoylating it and the NFAT5 protein preys include components of the CHTOP complex that desumoylate proteins, an action that should contribute to activation of NFAT5. PMID:26757802

Structured and Unstructured Binding of an Intrinsically Disordered Protein as Revealed by Atomistic Simulations.

PubMed

Ithuralde, Raúl Esteban; Roitberg, Adrián Enrique; Turjanski, Adrián Gustavo

2016-07-20

Intrinsically disordered proteins (IDPs) are a set of proteins that lack a definite secondary structure in solution. IDPs can acquire tertiary structure when bound to their partners; therefore, the recognition process must also involve protein folding. The nature of the transition state (TS), structured or unstructured, determines the binding mechanism. The characterization of the TS has become a major challenge for experimental techniques and molecular simulations approaches since diffusion, recognition, and binding is coupled to folding. In this work we present atomistic molecular dynamics (MD) simulations that sample the free energy surface of the coupled folding and binding of the transcription factor c-myb to the cotranscription factor CREB binding protein (CBP). This process has been recently studied and became a model to study IDPs. Despite the plethora of available information, we still do not know how c-myb binds to CBP. We performed a set of atomistic biased MD simulations running a total of 15.6 μs. Our results show that c-myb folds very fast upon binding to CBP with no unique pathway for binding. The process can proceed through both structured or unstructured TS's with similar probabilities. This finding reconciles previous seemingly different experimental results. We also performed Go-type coarse-grained MD of several structured and unstructured models that indicate that coupled folding and binding follows a native contact mechanism. To the best of our knowledge, this is the first atomistic MD simulation that samples the free energy surface of the coupled folding and binding processes of IDPs.

Investigation of effect of leg support elevation timing on the horizontal force acting on the buttocks in a reclining wheelchair.

PubMed

Kobara, Kenichi; Takahashi, Hisashi; Fujita, Daisuke; Osaka, Hiroshi; Ito, Tomotaka; Suehiro, Tadanobu; Watanabe, Susumu

2015-08-01

[Purpose] The purpose of this study was to investigate the effect of the timing of leg support elevation on the horizontal force acting on the buttocks in a reclining wheelchair. [Subjects and Methods] The participants were 17 healthy men. Two experimental conditions were tested: the leg-down and leg-up conditions. The back support was reclined at increasing angles, from the initial upright position (IUP), proceeding to the fully reclined position (FRP), and returned to the upright position (RUP). The posterior inclination phase was from IUP to FRP, and the returning inclination phase was from FRP to RUP. [Results] The horizontal force under the leg-up condition was significantly higher than that under the leg-down condition in all positions of back support. [Conclusion] The leg supports should be positioned downward before reclining the back support of a wheelchair.

Limb-Nadir Matching for Tropospheric NO2: A New Algorithm in the SCIAMACHY Operational Level 2 Processor

NASA Astrophysics Data System (ADS)

Meringer, Markus; Gretschany, Sergei; Lichtenberg, Gunter; Hilboll, Andreas; Richter, Andreas; Burrows, John P.

2015-11-01

SCIAMACHY (SCanning Imaging Absorption spectroMeter for Atmospheric ChartographY) aboard ESA's environmental satellite ENVISAT observed the Earth's atmosphere in limb, nadir, and solar/lunar occultation geometries covering the UV-Visible to NIR spectral range. Limb and nadir geometries were the main operation modes for the retrieval of scientific data. The new version 6 of ESA's level 2 processor now provides for the first time an operational algorithm to combine measurements of these two geometries in order to generate new products. As a first instance the retrieval of tropospheric NO2 has been implemented based on IUP-Bremen's reference algorithm. We will detail the single processing steps performed by the operational limb-nadir matching algorithm and report the results of comparisons with the scientific tropospheric NO2 products of IUP and the Tropospheric Emission Monitoring Internet Service (TEMIS).

Application of linker technique to trap transiently interacting protein complexes for structural studies

PubMed Central

Reddy Chichili, Vishnu Priyanka; Kumar, Veerendra; Sivaraman, J.

2016-01-01

Protein-protein interactions are key events controlling several biological processes. We have developed and employed a method to trap transiently interacting protein complexes for structural studies using glycine-rich linkers to fuse interacting partners, one of which is unstructured. Initial steps involve isothermal titration calorimetry to identify the minimum binding region of the unstructured protein in its interaction with its stable binding partner. This is followed by computational analysis to identify the approximate site of the interaction and to design an appropriate linker length. Subsequently, fused constructs are generated and characterized using size exclusion chromatography and dynamic light scattering experiments. The structure of the chimeric protein is then solved by crystallization, and validated both in vitro and in vivo by substituting key interacting residues of the full length, unlinked proteins with alanine. This protocol offers the opportunity to study crucial and currently unattainable transient protein interactions involved in various biological processes. PMID:26985443

Functional Tat transport of unstructured, small, hydrophilic proteins.

PubMed

Richter, Silke; Lindenstrauss, Ute; Lücke, Christian; Bayliss, Richard; Brüser, Thomas

2007-11-16

The twin-arginine translocation (Tat) system is a protein translocation system that is adapted to the translocation of folded proteins across biological membranes. An understanding of the folding requirements for Tat substrates is of fundamental importance for the elucidation of the transport mechanism. We now demonstrate for the first time Tat transport for fully unstructured proteins, using signal sequence fusions to naturally unfolded FG repeats from the yeast Nsp1p nuclear pore protein. The transport of unfolded proteins becomes less efficient with increasing size, consistent with only a single interaction between the system and the substrate. Strikingly, the introduction of six residues from the hydrophobic core of a globular protein completely blocked translocation. Physiological data suggest that hydrophobic surface patches abort transport at a late stage, most likely by membrane interactions during transport. This study thus explains the observed restriction of the Tat system to folded globular proteins on a molecular level.

Behavioral and Physiological Analyses of Parturition In Pregnant Rats: Insights Derived from Intrauterine Telemetry

NASA Technical Reports Server (NTRS)

Villareal, J.; Mallery, E.; Lynch, A.; Mills, N.; Baer, L.; Wade, C.; Ronca, A.; Dalton, Donnie (Technical Monitor)

2002-01-01

During labor and birth, fetuses are exposed to considerable physical stimulation associated with labor contractions and expulsion from the womb These forces are important for the neonates' adaptation to tile extrauterine environment. To further our understanding of the relationship between labor and postpartum outcome, we developed a novel method for measuring intrauterine pressure (IUP) in freely-moving, late pregnant and parturient rats that enables us to make precise, reliable measures of the forces experienced by rat fetuses during parturition. A small (1.25 x 4 cm) telemetric blood pressure sensor was fitted within a fluid-filled balloon, similar in size to a full term rat fetus. On Gestational day (G) 19 of the rats' 22/23 day pregnancy, each dam was anesthetized and a balloon/sensor unit surgically implanted within the uterus following removal of two fetuses. Comparisons were made between sensor-implanted dams (IMPL) and a control conditions: 1) LAP-R, laparotomy with two fetuses removed or 2) LAP-NR, laparotomy with no fetuses removed. IUP signals were sampled at 10s intervals from the IMPL dams during labor and birth. Dams in all three conditions were videorecorded enabling us to analyze the effect of the implant on behavioral expressions of parturition. Contraction frequency, duration, pup-to-pup birth intervals and pup-oriented activities of the dams measured from one hour prior to the first pup birth until the birth of the third pup were unaffected by the sensor implant. Intrauterine telemetry of freely-moving dams offers significant advantages over conventional hardwired IUP measurement techniques. These findings establish and validate intrauterine telemetry as a reliable, non-invasive technique for quantifying pressures associated with parturition.

Uncovering the role of the flexible C-terminal tail: A model study with Strep-tagged GFP.

PubMed

Lassalle, Michael W; Kondou, Shinobu

2016-06-01

Recently, it has been recognized that, much like an electric current in an electric circuit, dynamic disruptions from flexible, unstructured regions distal to the active region are transferred through the contact network to the active site and influence protein stability and/or function. As transmembrane proteins frequently possess the β-barrel structure, studies of proteins with this topology are required. The unstructured lid segments of the β-barrel GFP protein are conserved and could play a role in the backbone stabilization required for chromophore function. A study of the disordered C-terminus and the function within the lid is necessary. In this study, we entirely truncated the flexible C-terminal tail and investigated the N-terminal Strep-tagged GFP by fluorescence spectroscopy, and the temperature- and GdnHCl-induced unfolding by circular dichroism. The introduction of the unstructured Strep-tag itself changed the unfolding pathway. Truncating the entire flexible tail did not decrease the fluorescence intensity to a large extent; however, the protein stability changed dramatically. The temperature for half-denaturation T 1/2 changed significantly from 79 °C for the wild-type to 72.8 °C for the mutant. Unfolding kinetics at different temperatures have been induced by 4 M GdnHCl, and the apparent Arrhenius activation energy decreased by 40% as compared to the wild-type.

Rational design of p53, an intrinsically unstructured protein, for the fabrication of novel molecular sensors.

PubMed

Geddie, Melissa L; O'Loughlin, Taryn L; Woods, Kristen K; Matsumura, Ichiro

2005-10-21

The dominant paradigm of protein engineering is structure-based site-directed mutagenesis. This rational approach is generally more effective for the engineering of local properties, such as substrate specificity, than global ones such as allostery. Previous workers have modified normally unregulated reporter enzymes, including beta-galactosidase, alkaline phosphatase, and beta-lactamase, so that the engineered versions are activated (up to 4-fold) by monoclonal antibodies. A reporter that could easily be "reprogrammed" for the facile detection of novel effectors (binding or modifying activities) would be useful in high throughput screens for directed evolution or drug discovery. Here we describe a straightforward and general solution to this potentially difficult design problem. The transcription factor p53 is normally regulated by a variety of post-translational modifications. The insertion of peptides into intrinsically unstructured domains of p53 generated variants that were activated up to 100-fold by novel effectors (proteases or antibodies). An engineered p53 was incorporated into an existing high throughput screen for the detection of human immunodeficiency virus protease, an arbitrarily chosen novel effector. These results suggest that the molecular recognition properties of intrinsically unstructured proteins are relatively easy to engineer and that the absence of crystal structures should not deter the rational engineering of this class of proteins.

Designing the OPAC User Interface to Improve Access and Retrieval.

ERIC Educational Resources Information Center

Basista, Thomas; And Others

1991-01-01

Discussion of problems with retrieval of records in library online public access catalogs (OPACs) focuses on an ongoing research project at the Indiana University of Pennsylvania (IUP) that has been trying to improve subject retrieval vocabulary control using natural and thesaural language and on the design of a good graphical user interface.…

Evaluation of the use of five laboratory-determined ozone absorption cross sections in Brewer and Dobson retrieval algorithms

NASA Astrophysics Data System (ADS)

Redondas, A.; Evans, R.; Stuebi, R.; Köhler, U.; Weber, M.

2014-02-01

The primary ground-based instruments used to report total column ozone (TOC) are Brewer and Dobson spectrophotometers in separate networks. These instruments make measurements of the UV irradiances, and through a well-defined process, a TOC value is produced. Inherent to the algorithm is the use of a laboratory-determined cross-section data set. We used five ozone cross-section data sets: three data sets that are based on measurements of Bass and Paur; one derived from Daumont, Brion and Malicet (DBM); and a new set determined by Institute of Experimental Physics (IUP), University of Bremen. The three Bass and Paur (1985) sets are as follows: quadratic temperature coefficients from the IGACO (a glossary is provided in Appendix A) web page (IGQ4), the Brewer network operational calibration set (BOp), and the set used by Bernhard et al. (2005) in the reanalysis of the Dobson absorption coefficient values (B05). The ozone absorption coefficients for Brewer and Dobson instruments are then calculated using the normal Brewer operative method, which is essentially the same as that used for Dobson instruments. Considering the standard TOC algorithm for the Brewer instruments and comparing to the Brewer standard operational calibration data set, using the slit functions for the individual instruments, we find the IUP data set changes the calculated TOC by -0.5%, the DBM data set changes the calculated TOC by -3.2%, and the IGQ4 data set at -45 °C changes the calculated TOC by +1.3%. Considering the standard algorithm for the Dobson instruments, and comparing to results using the official 1992 ozone absorption coefficients values and the single set of slit functions defined for all Dobson instruments, the calculated TOC changes by +1%, with little variation depending on which data set is used. We applied the changes to the European Dobson and Brewer reference instruments during the Izaña 2012 Absolute Calibration Campaign. With the application of a common Langley calibration and the IUP cross section, the differences between Brewer and Dobson data sets vanish, whereas using those of Bass and Paur and DBM produces differences of 1.5 and 2%, respectively. A study of the temperature dependence of these cross-section data sets is presented using the Arosa, Switzerland, total ozone record of 2003-2006, obtained from two Brewer-type instruments and one Dobson-type instrument, combined with the stratospheric ozone and temperature profiles from the Payerne soundings in the same period. The seasonal dependence of the differences between the results from the various instruments is greatly reduced with the application of temperature-dependent absorption coefficients, with the greatest reduction obtained using the IUP data set.

Teaching Hands-On Linux Host Computer Security

ERIC Educational Resources Information Center

Shumba, Rose

2006-01-01

In the summer of 2003, a project to augment and improve the teaching of information assurance courses was started at IUP. Thus far, ten hands-on exercises have been developed. The exercises described in this article, and presented in the appendix, are based on actions required to secure a Linux host. Publicly available resources were used to…

Isolation and Compositional Analysis of a CP12-Associated Complex of Calvin Cycle Enzymes from Nicotiana tabacum

USDA-ARS?s Scientific Manuscript database

CP12 is a small intrinsically unstructured protein that forms a multiprotein complex with two Calvin Cycle enzymes, phosphoribulokinase (PRK) and NAD(P)-dependent glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The complex can be reconstituted in vitro from recombinant proteins under conditions t...

The unstructured linker arms of Mlh1-Pms1 are important for interactions with DNA during mismatch repair

PubMed Central

Plys, Aaron J.; Rogacheva, Maria V.; Greene, Eric C.; Alani, Eric

2012-01-01

DNA mismatch repair (MMR) models have proposed that MSH proteins identify DNA polymerase errors while interacting with the DNA replication fork. MLH proteins (primarily Mlh1-Pms1 in baker’s yeast) then survey the genome for lesion-bound MSH proteins. The resulting MSH-MLH complex formed at a DNA lesion initiates downstream steps in repair. MLH proteins act as dimers and contain long (20 – 30 nanometers) unstructured arms that connect two terminal globular domains. These arms can vary between 100 to 300 amino acids in length, are highly divergent between organisms, and are resistant to amino acid substitutions. To test the roles of the linker arms in MMR, we engineered a protease cleavage site into the Mlh1 linker arm domain of baker’s yeast Mlh1-Pms1. Cleavage of the Mlh1 linker arm in vitro resulted in a defect in Mlh1-Pms1 DNA binding activity, and in vivo proteolytic cleavage resulted in a complete defect in MMR. We then generated a series of truncation mutants bearing Mlh1 and Pms1 linker arms of varying lengths. This work revealed that MMR is greatly compromised when portions of the Mlh1 linker are removed, whereas repair is less sensitive to truncation of the Pms1 linker arm. Purified complexes containing truncations in Mlh1 and Pms1 linker arms were analyzed and found to have differential defects in DNA binding that also correlated with the ability to form a ternary complex with Msh2-Msh6 and mismatch DNA. These observations are consistent with the unstructured linker domains of MLH proteins providing distinct interactions with DNA during MMR. PMID:22659005

Rapid Proteasomal Degradation of Posttranscriptional Regulators of the TIS11/Tristetraprolin Family Is Induced by an Intrinsically Unstructured Region Independently of Ubiquitination

PubMed Central

Ngoc, Long Vo; Wauquier, Corinne; Soin, Romuald; Bousbata, Sabrina; Twyffels, Laure; Kruys, Véronique

2014-01-01

The TIS11/tristetraprolin (TTP) CCCH tandem zinc finger proteins are major effectors in the destabilization of mRNAs bearing AU-rich elements (ARE) in their 3′ untranslated regions. In this report, we demonstrate that the Drosophila melanogaster dTIS11 protein is short-lived due to its rapid ubiquitin-independent degradation by the proteasome. Our data indicate that this mechanism is tightly associated with the intrinsically unstructured, disordered N- and C-terminal domains of the protein. Furthermore, we show that TTP, the mammalian TIS11/TTP protein prototype, shares the same three-dimensional characteristics and is degraded by the same proteolytic pathway as dTIS11, thereby indicating that this mechanism has been conserved across evolution. Finally, we observed a phosphorylation-dependent inhibition of dTIS11 and TTP degradation by the proteasome in vitro, raising the possibility that such modifications directly affect proteasomal recognition for these proteins. As a group, RNA-binding proteins (RNA-BPs) have been described as enriched in intrinsically disordered regions, thus raising the possibility that the mechanism that we uncovered for TIS11/TTP turnover is widespread among other RNA-BPs. PMID:25246635

Conversion of Natively Unstructured α-Synuclein to Its α-Helical Conformation Significantly Attenuates Production of Reactive Oxygen Species

PubMed Central

Zhou, Binbin; Hao, Yuanqiang; Wang, Chengshan; Li, Ding; Liu, You-Nian; Zhou, Feimeng

2012-01-01

The intracellular α-synuclein (α-syn) protein, whose conformational change and aggregation have been closely linked to the pathology of Parkingson’s disease (PD), is highly populated at the presynaptic termini and remains there in the α-helical conformation. In this study, circular dichroism confirmed that natively unstructured α-syn in aqueous solution was transformed to its α-helical conformation upon addition of trifluoroethanol (TFE). Electrochemical and UV–visible spectroscopic experiments reveal that both Cu(I) and Cu(II) are stabilized, with the former being stabilized by about two orders of magnitude. Compared to unstructured α-syn (Binolfi et al., J. Am. Chem. Soc. 133 (2011) 194–196), α-helical α-syn stabilizes Cu(I) by more than three orders of magnitude. Through the measurements of H2O2 and hydroxyl radicals (OH•) in solutions containing different forms of Cu(II) (free and complexed by unstructured or α-helical α-syn), we demonstrate that the significantly enhanced Cu(I) binding affinity helps inhibit the production of highly toxic reactive oxygen species, especially the hydroxyl radicals. Our study provides strong evidence that, as a possible means to prevent neuronal cell damage, conversion of the natively unstructured α-syn to its α-helical conformation in vivo could significantly attenuate the copper-modulated ROS production. PMID:23123341

Implementing Digital Individual Development Planning in Teacher Education: The Challenges of Communication in Relation to the Development of ICT-Supported Methods

ERIC Educational Resources Information Center

Granberg, Carina

2009-01-01

This paper presents a study of the experiences of a group of teacher educators during the 2006-2007 academic year, when they participated in a project to try out and implement digital individual development planning (which in Swedish is digital "Individuella Utvecklings-Planer" or IUP) in a teacher education faculty at a Swedish…

RCK: accurate and efficient inference of sequence- and structure-based protein-RNA binding models from RNAcompete data.

PubMed

Orenstein, Yaron; Wang, Yuhao; Berger, Bonnie

2016-06-15

Protein-RNA interactions, which play vital roles in many processes, are mediated through both RNA sequence and structure. CLIP-based methods, which measure protein-RNA binding in vivo, suffer from experimental noise and systematic biases, whereas in vitro experiments capture a clearer signal of protein RNA-binding. Among them, RNAcompete provides binding affinities of a specific protein to more than 240 000 unstructured RNA probes in one experiment. The computational challenge is to infer RNA structure- and sequence-based binding models from these data. The state-of-the-art in sequence models, Deepbind, does not model structural preferences. RNAcontext models both sequence and structure preferences, but is outperformed by GraphProt. Unfortunately, GraphProt cannot detect structural preferences from RNAcompete data due to the unstructured nature of the data, as noted by its developers, nor can it be tractably run on the full RNACompete dataset. We develop RCK, an efficient, scalable algorithm that infers both sequence and structure preferences based on a new k-mer based model. Remarkably, even though RNAcompete data is designed to be unstructured, RCK can still learn structural preferences from it. RCK significantly outperforms both RNAcontext and Deepbind in in vitro binding prediction for 244 RNAcompete experiments. Moreover, RCK is also faster and uses less memory, which enables scalability. While currently on par with existing methods in in vivo binding prediction on a small scale test, we demonstrate that RCK will increasingly benefit from experimentally measured RNA structure profiles as compared to computationally predicted ones. By running RCK on the entire RNAcompete dataset, we generate and provide as a resource a set of protein-RNA structure-based models on an unprecedented scale. Software and models are freely available at http://rck.csail.mit.edu/ bab@mit.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

Knowledge representation and management: transforming textual information into useful knowledge.

PubMed

Rassinoux, A-M

2010-01-01

To summarize current outstanding research in the field of knowledge representation and management. Synopsis of the articles selected for the IMIA Yearbook 2010. Four interesting papers, dealing with structured knowledge, have been selected for the section knowledge representation and management. Combining the newest techniques in computational linguistics and natural language processing with the latest methods in statistical data analysis, machine learning and text mining has proved to be efficient for turning unstructured textual information into meaningful knowledge. Three of the four selected papers for the section knowledge representation and management corroborate this approach and depict various experiments conducted to .extract meaningful knowledge from unstructured free texts such as extracting cancer disease characteristics from pathology reports, or extracting protein-protein interactions from biomedical papers, as well as extracting knowledge for the support of hypothesis generation in molecular biology from the Medline literature. Finally, the last paper addresses the level of formally representing and structuring information within clinical terminologies in order to render such information easily available and shareable among the health informatics community. Delivering common powerful tools able to automatically extract meaningful information from the huge amount of electronically unstructured free texts is an essential step towards promoting sharing and reusability across applications, domains, and institutions thus contributing to building capacities worldwide.

AAA-ATPases in Protein Degradation

PubMed Central

Yedidi, Ravikiran S.; Wendler, Petra; Enenkel, Cordula

2017-01-01

Proteolytic machineries containing multisubunit protease complexes and AAA-ATPases play a key role in protein quality control and the regulation of protein homeostasis. In these protein degradation machineries, the proteolytically active sites are formed by either threonines or serines which are buried inside interior cavities of cylinder-shaped complexes. In eukaryotic cells, the proteasome is the most prominent protease complex harboring AAA-ATPases. To degrade protein substrates, the gates of the axial entry ports of the protease need to be open. Gate opening is accomplished by AAA-ATPases, which form a hexameric ring flanking the entry ports of the protease. Protein substrates with unstructured domains can loop into the entry ports without the assistance of AAA-ATPases. However, folded proteins require the action of AAA-ATPases to unveil an unstructured terminus or domain. Cycles of ATP binding/hydrolysis fuel the unfolding of protein substrates which are gripped by loops lining up the central pore of the AAA-ATPase ring. The AAA-ATPases pull on the unfolded polypeptide chain for translocation into the proteolytic cavity of the protease. Conformational changes within the AAA-ATPase ring and the adjacent protease chamber create a peristaltic movement for substrate degradation. The review focuses on new technologies toward the understanding of the function and structure of AAA-ATPases to achieve substrate recognition, unfolding and translocation into proteasomes in yeast and mammalian cells and into proteasome-equivalent proteases in bacteria and archaea. PMID:28676851

AAA-ATPases in Protein Degradation.

PubMed

Yedidi, Ravikiran S; Wendler, Petra; Enenkel, Cordula

2017-01-01

Proteolytic machineries containing multisubunit protease complexes and AAA-ATPases play a key role in protein quality control and the regulation of protein homeostasis. In these protein degradation machineries, the proteolytically active sites are formed by either threonines or serines which are buried inside interior cavities of cylinder-shaped complexes. In eukaryotic cells, the proteasome is the most prominent protease complex harboring AAA-ATPases. To degrade protein substrates, the gates of the axial entry ports of the protease need to be open. Gate opening is accomplished by AAA-ATPases, which form a hexameric ring flanking the entry ports of the protease. Protein substrates with unstructured domains can loop into the entry ports without the assistance of AAA-ATPases. However, folded proteins require the action of AAA-ATPases to unveil an unstructured terminus or domain. Cycles of ATP binding/hydrolysis fuel the unfolding of protein substrates which are gripped by loops lining up the central pore of the AAA-ATPase ring. The AAA-ATPases pull on the unfolded polypeptide chain for translocation into the proteolytic cavity of the protease. Conformational changes within the AAA-ATPase ring and the adjacent protease chamber create a peristaltic movement for substrate degradation. The review focuses on new technologies toward the understanding of the function and structure of AAA-ATPases to achieve substrate recognition, unfolding and translocation into proteasomes in yeast and mammalian cells and into proteasome-equivalent proteases in bacteria and archaea.

The Kinetics of Evolution of Water Vapor Clusters in Air

DTIC Science & Technology

1975-12-01

Academy Annapnlis, Mazylsnd 21402 D IUP 17% Work Supported by: Power Branch and Atmospheric Sciences Program, Office of Naval Research and Naval Air...to experiments in supersonic nozzles. The patient support of the Power Branch and the Atmospheric Sciences Program, Office of Naval Research over...the start by relying on the dioital compxiter from the start of development. Time- shared computer facilities were provided by the Naval Weapons Lab

A software platform for continuum modeling of ion channels based on unstructured mesh

NASA Astrophysics Data System (ADS)

Tu, B.; Bai, S. Y.; Chen, M. X.; Xie, Y.; Zhang, L. B.; Lu, B. Z.

2014-01-01

Most traditional continuum molecular modeling adopted finite difference or finite volume methods which were based on a structured mesh (grid). Unstructured meshes were only occasionally used, but an increased number of applications emerge in molecular simulations. To facilitate the continuum modeling of biomolecular systems based on unstructured meshes, we are developing a software platform with tools which are particularly beneficial to those approaches. This work describes the software system specifically for the simulation of a typical, complex molecular procedure: ion transport through a three-dimensional channel system that consists of a protein and a membrane. The platform contains three parts: a meshing tool chain for ion channel systems, a parallel finite element solver for the Poisson-Nernst-Planck equations describing the electrodiffusion process of ion transport, and a visualization program for continuum molecular modeling. The meshing tool chain in the platform, which consists of a set of mesh generation tools, is able to generate high-quality surface and volume meshes for ion channel systems. The parallel finite element solver in our platform is based on the parallel adaptive finite element package PHG which wass developed by one of the authors [1]. As a featured component of the platform, a new visualization program, VCMM, has specifically been developed for continuum molecular modeling with an emphasis on providing useful facilities for unstructured mesh-based methods and for their output analysis and visualization. VCMM provides a graphic user interface and consists of three modules: a molecular module, a meshing module and a numerical module. A demonstration of the platform is provided with a study of two real proteins, the connexin 26 and hemolysin ion channels.

Protein conformational disorder and enzyme catalysis.

PubMed

Schulenburg, Cindy; Hilvert, Donald

2013-01-01

Though lacking a well-defined three-dimensional structure, intrinsically unstructured proteins are ubiquitous in nature. These molecules play crucial roles in many cellular processes, especially signaling and regulation. Surprisingly, even enzyme catalysis can tolerate substantial disorder. This observation contravenes conventional wisdom but is relevant to an understanding of how protein dynamics modulates enzyme function. This chapter reviews properties and characteristics of disordered proteins, emphasizing examples of enzymes that lack defined structures, and considers implications of structural disorder for catalytic efficiency and evolution.

Conformational landscape of an amyloid intra-cellular domain and Landau-Ginzburg-Wilson paradigm in protein dynamics

NASA Astrophysics Data System (ADS)

Dai, Jin; Niemi, Antti J.; He, Jianfeng

2016-07-01

The Landau-Ginzburg-Wilson paradigm is proposed as a framework, to investigate the conformational landscape of intrinsically unstructured proteins. A universal Cα-trace Landau free energy is deduced from general symmetry considerations, with the ensuing all-atom structure modeled using publicly available reconstruction programs Pulchra and Scwrl. As an example, the conformational stability of an amyloid precursor protein intra-cellular domain (AICD) is inspected; the reference conformation is the crystallographic structure with code 3DXC in Protein Data Bank (PDB) that describes a heterodimer of AICD and a nuclear multi-domain adaptor protein Fe65. Those conformations of AICD that correspond to local or near-local minima of the Landau free energy are identified. For this, the response of the original 3DXC conformation to variations in the ambient temperature is investigated, using the Glauber algorithm. The conclusion is that in isolation the AICD conformation in 3DXC must be unstable. A family of degenerate conformations that minimise the Landau free energy is identified, and it is proposed that the native state of an isolated AICD is a superposition of these conformations. The results are fully in line with the presumed intrinsically unstructured character of isolated AICD and should provide a basis for a systematic analysis of AICD structure in future NMR experiments.

Anxiety associated with diagnostic uncertainty in early pregnancy.

PubMed

Richardson, A; Raine-Fenning, N; Deb, S; Campbell, B; Vedhara, K

2017-08-01

To determine anxiety levels of women presenting to an early pregnancy assessment unit (EPAU) with abdominal pain and/or vaginal bleeding and to assess how these levels change over time and according to ultrasonographic diagnosis. We undertook a prospective cohort study in an EPAU in a large UK teaching hospital. Women with abdominal pain and/or vaginal bleeding in early pregnancy (< 12 weeks' gestation) presenting for the first time were eligible for inclusion in the study. State anxiety levels were assessed using the standardized short form of Spielberger's state-trait anxiety inventory (STAI) on three occasions (before, immediately after and 48-72 hours after an ultrasound scan). Scores were correlated with ultrasonographic diagnosis. The diagnosis was either certain or uncertain. Certain diagnoses were either positive, i.e. a viable intrauterine pregnancy (IUP), or negative, i.e. a non-viable IUP or ectopic pregnancy. Uncertain diagnoses included pregnancy of unknown location and pregnancy of uncertain viability. Statistical analysis involved mixed ANOVAs and the post-hoc Tukey-Kramer test. A total of 160 women were included in the study. Anxiety levels decreased over time for women with a certain diagnosis (n = 128), even when negative (n = 64), and increased over time for women with an uncertain diagnosis (n = 32). Before the ultrasound examination, anxiety levels were high (STAI value, 21.96 ± 1.11) and there was no significant difference between the five groups. Immediately after the ultrasound examination, anxiety levels were lower in the viable IUP group (n = 64; 7.75 ± 1.13) than in any other group. The difference between the five groups was significant (P < 0.005). After 48-72 hours, women with a certain diagnosis had significantly lower anxiety levels than had those with an uncertain diagnosis (10.77 ± 4.30 vs 22.94 ± 1.65; P < 0.005). The experience of abdominal pain and/or vaginal bleeding in early pregnancy is highly anxiogenic. Following an ultrasound examination, the certainty of the diagnosis affects anxiety levels more than does the positive or negative connotations associated with the diagnosis per se. Healthcare providers should be aware of this when communicating uncertain diagnoses. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Celecoxib Encapsulation in β-Casein Micelles: Structure, Interactions, and Conformation.

PubMed

Turovsky, Tanya; Khalfin, Rafail; Kababya, Shifi; Schmidt, Asher; Barenholz, Yechezkel; Danino, Dganit

2015-07-07

β-Casein is a 24 kDa natural protein that has an open conformation and almost no folded or secondary structure, and thus is classified as an intrinsically unstructured protein. At neutral pH, β-casein has an amphiphilic character. Therefore, in contrast to most unstructured proteins that remain monomeric in solution, β-casein self-assembles into well-defined core-shell micelles. We recently developed these micelles as potential carriers for oral administration of poorly water-soluble pharmaceuticals, using celecoxib as a model drug. Herein we present deep and precise insight into the physicochemical characteristics of the protein-drug formulation, both in bulk solution and in dry form, emphasizing drug conformation, packing properties and aggregation state. In addition, the formulation is extensively studied in terms of structure and morphology, protein/drug interactions and physical stability. Particularly, NMR measurements indicated strong drug-protein interactions and noncrystalline drug conformation, which is expected to improve drug solubility and bioavailability. Small-angle X-ray scattering (SAXS) and cryogenic transmission electron microscopy (cryo-TEM) were combined for nanostructural characterization, proving that drug-protein interactions lead to well-defined spheroidal micelles that become puffier and denser upon drug loading. Dynamice light scattering (DLS), turbidity measurements, and visual observations complemented the analysis for determining formulation structure, interactions, and stability. Additionally, it was shown that the loaded micelles retain their properties through freeze-drying and rehydration, providing long-term physical and chemical stability. Altogether, the formulation seems greatly promising for oral drug delivery.

Radiative transfer modeling through terrestrial atmosphere and ocean accounting for inelastic processes: Software package SCIATRAN

NASA Astrophysics Data System (ADS)

Rozanov, V. V.; Dinter, T.; Rozanov, A. V.; Wolanin, A.; Bracher, A.; Burrows, J. P.

2017-06-01

SCIATRAN is a comprehensive software package which is designed to model radiative transfer processes in the terrestrial atmosphere and ocean in the spectral range from the ultraviolet to the thermal infrared (0.18-40 μm). It accounts for multiple scattering processes, polarization, thermal emission and ocean-atmosphere coupling. The main goal of this paper is to present a recently developed version of SCIATRAN which takes into account accurately inelastic radiative processes in both the atmosphere and the ocean. In the scalar version of the coupled ocean-atmosphere radiative transfer solver presented by Rozanov et al. [61] we have implemented the simulation of the rotational Raman scattering, vibrational Raman scattering, chlorophyll and colored dissolved organic matter fluorescence. In this paper we discuss and explain the numerical methods used in SCIATRAN to solve the scalar radiative transfer equation including trans-spectral processes, and demonstrate how some selected radiative transfer problems are solved using the SCIATRAN package. In addition we present selected comparisons of SCIATRAN simulations with those published benchmark results, independent radiative transfer models, and various measurements from satellite, ground-based, and ship-borne instruments. The extended SCIATRAN software package along with a detailed User's Guide is made available for scientists and students, who are undertaking their own research typically at universities, via the web page of the Institute of Environmental Physics (IUP), University of Bremen: http://www.iup.physik.uni-bremen.de.

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

Dai, Jin; He, Jianfeng, E-mail: Antti.Niemi@physics.uu.se, E-mail: hjf@bit.edu.cn; Niemi, Antti J., E-mail: Antti.Niemi@physics.uu.se, E-mail: hjf@bit.edu.cn

The Landau-Ginzburg-Wilson paradigm is proposed as a framework, to investigate the conformational landscape of intrinsically unstructured proteins. A universal Cα-trace Landau free energy is deduced from general symmetry considerations, with the ensuing all-atom structure modeled using publicly available reconstruction programs Pulchra and Scwrl. As an example, the conformational stability of an amyloid precursor protein intra-cellular domain (AICD) is inspected; the reference conformation is the crystallographic structure with code 3DXC in Protein Data Bank (PDB) that describes a heterodimer of AICD and a nuclear multi-domain adaptor protein Fe65. Those conformations of AICD that correspond to local or near-local minima of themore » Landau free energy are identified. For this, the response of the original 3DXC conformation to variations in the ambient temperature is investigated, using the Glauber algorithm. The conclusion is that in isolation the AICD conformation in 3DXC must be unstable. A family of degenerate conformations that minimise the Landau free energy is identified, and it is proposed that the native state of an isolated AICD is a superposition of these conformations. The results are fully in line with the presumed intrinsically unstructured character of isolated AICD and should provide a basis for a systematic analysis of AICD structure in future NMR experiments.« less

Refinement and Verification of Predictive Models of Suspended Sediment Dispersion and Desorption of Toxics from Dredged Sediments.

DTIC Science & Technology

1982-07-01

C ~ DO 680 J=1,NSTEP FOREX =SQRT(ADELX(J+1) *4.* (EZ* ( +EXPCO*EXP( - ’ADELX(J+1)/100.)))) DO 680 IZ=1,21 AZ=(IZ-1) *DELZ TOP=(AZ+XL )/ FOREX - 166 ET...ERF(TOP) BOT= (AZ-XL )/ FOREX EB=ERF (BOT) Z( IZ,J+1)=0. 5*(ET-EB) 680 CONTINUE C C START FINITE DIFFERENCE SOLUTION IF(ISCE.EQ.3)GO TO 25 DO 100 I=IUP

The Unstructured Paramyxovirus Nucleocapsid Protein Tail Domain Modulates Viral Pathogenesis through Regulation of Transcriptase Activity.

PubMed

Thakkar, Vidhi D; Cox, Robert M; Sawatsky, Bevan; da Fontoura Budaszewski, Renata; Sourimant, Julien; Wabbel, Katrin; Makhsous, Negar; Greninger, Alexander L; von Messling, Veronika; Plemper, Richard K

2018-04-15

The paramyxovirus replication machinery comprises the viral large (L) protein and phosphoprotein (P-protein) in addition to the nucleocapsid (N) protein, which encapsidates the single-stranded RNA genome. Common to paramyxovirus N proteins is a C-terminal tail (Ntail). The mechanistic role and relevance for virus replication of the structurally disordered central Ntail section are unknown. Focusing initially on members of the Morbillivirus genus, a series of measles virus (MeV) and canine distemper virus (CDV) N proteins were generated with internal deletions in the unstructured tail section. N proteins with large tail truncations remained bioactive in mono- and polycistronic minireplicon assays and supported efficient replication of recombinant viruses. Bioactivity of Ntail mutants extended to N proteins derived from highly pathogenic Nipah virus. To probe an effect of Ntail truncations on viral pathogenesis, recombinant CDVs were analyzed in a lethal CDV/ferret model of morbillivirus disease. The recombinant viruses displayed different stages of attenuation ranging from ameliorated clinical symptoms to complete survival of infected animals, depending on the molecular nature of the Ntail truncation. Reinfection of surviving animals with pathogenic CDV revealed robust protection against a lethal challenge. The highly attenuated virus was genetically stable after ex vivo passaging and recovery from infected animals. Mechanistically, gradual viral attenuation coincided with stepwise altered viral transcriptase activity in infected cells. These results identify the central Ntail section as a determinant for viral pathogenesis and establish a novel platform to engineer gradual virus attenuation for next-generation paramyxovirus vaccine design. IMPORTANCE Investigating the role of the paramyxovirus N protein tail domain (Ntail) in virus replication, we demonstrated in this study that the structurally disordered central Ntail region is a determinant for viral pathogenesis. We show that internal deletions in this Ntail region of up to 55 amino acids in length are compatible with efficient replication of recombinant viruses in cell culture but result in gradual viral attenuation in a lethal canine distemper virus (CDV)/ferret model. Mechanistically, we demonstrate a role of the intact Ntail region in the regulation of viral transcriptase activity. Recombinant viruses with Ntail truncations induce protective immunity against lethal challenge of ferrets with pathogenic CDV. This identification of the unstructured central Ntail domain as a nonessential paramyxovirus pathogenesis factor establishes a foundation for harnessing Ntail truncations for vaccine engineering against emerging and reemerging members of the paramyxovirus family. Copyright © 2018 American Society for Microbiology.

The perfused swine uterus model: long-term perfusion

PubMed Central

2012-01-01

Background It has previously been shown that the viability of swine uteri can be maintained within the physiological range in an open perfusion model for up to 8 hours. The aim of this study was to assess medium- to long-term perfusion of swine uteri using a modified Krebs–Ringer bicarbonate buffer solution (KRBB) in the established open perfusion model. Methods In an experimental study at an infertility institute, 30 swine uteri were perfused: group 1: n = 11, KRBB; group 2: n = 8, modified KRBB with drainage of perfusate supernatant; group 3: n = 11, modified KRBB with drainage of perfusate every 2 h and substitution with fresh medium. Modified and conventional KRBB were compared with regard to survival and contraction parameters: intrauterine pressure (IUP), area under the curve (AUC), and frequency of contractions (F). Results Modified KRBB showed significantly higher IUP, AUC, and F values than perfusion with conventional KRBB. In group 3, the organ survival time of up to 17 h, with a 98% rate of effective contraction time, differed significantly from group 1 (P < 0.001). Conclusions Using modified KRBB in combination with perfusate substitution improves the open model for perfusion of swine uteri with regard to survival time and quality of contraction parameters. This model can be used for medium- to long-term perfusion of swine uteri, allowing further metabolic ex vivo studies in a cost-effective way and with little logistic effort. PMID:23241226

Discrete Molecular Dynamics Approach to the Study of Disordered and Aggregating Proteins.

PubMed

Emperador, Agustí; Orozco, Modesto

2017-03-14

We present a refinement of the Coarse Grained PACSAB force field for Discrete Molecular Dynamics (DMD) simulations of proteins in aqueous conditions. As the original version, the refined method provides good representation of the structure and dynamics of folded proteins but provides much better representations of a variety of unfolded proteins, including some very large, impossible to analyze by atomistic simulation methods. The PACSAB/DMD method also reproduces accurately aggregation properties, providing good pictures of the structural ensembles of proteins showing a folded core and an intrinsically disordered region. The combination of accuracy and speed makes the method presented here a good alternative for the exploration of unstructured protein systems.

Insights into the role of protein molecule size and structure on interfacial properties using designed sequences

PubMed Central

Dwyer, Mirjana Dimitrijev; He, Lizhong; James, Michael; Nelson, Andrew; Middelberg, Anton P. J.

2013-01-01

Mixtures of a large, structured protein with a smaller, unstructured component are inherently complex and hard to characterize at interfaces, leading to difficulties in understanding their interfacial behaviours and, therefore, formulation optimization. Here, we investigated interfacial properties of such a mixed system. Simplicity was achieved using designed sequences in which chemical differences had been eliminated to isolate the effect of molecular size and structure, namely a short unstructured peptide (DAMP1) and its longer structured protein concatamer (DAMP4). Interfacial tension measurements suggested that the size and bulk structuring of the larger molecule led to much slower adsorption kinetics. Neutron reflectometry at equilibrium revealed that both molecules adsorbed as a monolayer to the air–water interface (indicating unfolding of DAMP4 to give a chain of four connected DAMP1 molecules), with a concentration ratio equal to that in the bulk. This suggests the overall free energy of adsorption is equal despite differences in size and bulk structure. At small interfacial extensional strains, only molecule packing influenced the stress response. At larger strains, the effect of size became apparent, with DAMP4 registering a higher stress response and interfacial elasticity. When both components were present at the interface, most stress-dissipating movement was achieved by DAMP1. This work thus provides insights into the role of proteins' molecular size and structure on their interfacial properties, and the designed sequences introduced here can serve as effective tools for interfacial studies of proteins and polymers. PMID:23303222

Cellular abundance of Mps1 and the role of its carboxyl terminal tail in substrate recruitment.

PubMed

Sun, Tingting; Yang, Xiaomei; Wang, Wei; Zhang, Xiaojuan; Xu, Quanbin; Zhu, Songcheng; Kuchta, Robert; Chen, Guanjun; Liu, Xuedong

2010-12-03

Mps1 is a protein kinase that regulates normal mitotic progression and the spindle checkpoint in response to spindle damage. The levels of Mps1 are relatively low in cells during interphase but elevated in mitosis or upon activation of the spindle checkpoint, although the dynamic range of Mps1 expression and the Mps1 catalytic mechanism have not been carefully characterized. Our recent structural studies of the Mps1 kinase domain revealed that the carboxyl-terminal tail region of Mps1 is unstructured, raising the question of whether this region has any functional role in Mps1 catalysis. Here we first determined the cellular abundance of Mps1 during cell cycle progression and found that Mps1 levels vary between 60,000 per cell in early G(1) and 110,000 per cell during mitosis. We studied phosphorylation of a number of Mps1 substrates in vitro and in culture cells. Unexpectedly, we found that the unstructured carboxyl-terminal region of Mps1 plays an essential role in substrate recruitment. Kinetics studies using the purified recombinant wild type and mutant kinases indicate that the carboxyl-terminal tail is largely dispensable for autophosphorylation of Mps1 but critical for trans-phosphorylation of substrates in vitro and in cultured cells. Mps1 mutant without the unstructured tail region is defective in mediating spindle assembly checkpoint activation. Our results underscore the importance of the unstructured tail region of Mps1 in kinase activation.

Evaluation of the use of five laboratory determined ozone absorption cross sections in brewer and dobson retrieval algorithms

NASA Astrophysics Data System (ADS)

Redondas, A.; Evans, R.; Stuebi, R.; Köhler, U.; Weber, M.

2013-09-01

The primary ground-based instruments used to report total column ozone (TOC) are Brewer and Dobson Spectrophotometers, in separate networks. These instruments make measurements of the UV irradiances, and through a well-defined process a TOC value is produced. Inherent in the algorithm is the use of a laboratory determined cross-section data set. We used five ozone cross section data sets: three Bass and Paur, Daumont, Malicet and Brion (DMB) and a new Institute of Environmental Physics (IUP), University of Bremen, set. The three Bass and Paur (1985) sets are: quadratic temperature coefficients from IGACO web page (IGQ4), the Brewer network operational calibration set (BOp), and the set used by Bernhard et al. (2005), in the reanalysis of the Dobson absorption coefficient values (B05). The ozone absorption coefficients for Brewer and Dobson are then calculated using the normal Brewer operative method which is essentially the same as used on Dobson. Considering the standard TOC algorithm for the Brewer instruments and comparing to the Brewer standard operational calibration data set, using the slit functions for the individual instruments: we find the UIP data set changes the calculated TOC by -0.5%, the DBM data set changes the calculate TOC by -3.2%, and the IGQ4 data set at -45 °C changes the calculated TOC by +1.3%. Considering the standard algorithm for the Dobson instruments, and comparing to results using the official 1992 ozone absorption coefficients values and the single set of slit functions defined for all Dobson instruments, the calculated TOC changes by +1%, with little variation depending on which data set is used We applied the changes to the European Dobson and Brewer reference instruments during the Izaña 2012 Absolute Calibration Campaign. The application of a common Langley calibration and the IUP cross section the differences between Brewer and Dobson vanish whereas using Bass and Paur and DBM produce differences of 1.5% and 2% respectively. A study of temperature dependence of these cross section (XS) data sets is presented using the Arosa, Switzerland total ozone record of 2003-2006, obtained from two Brewer instrument types and a Dobson instrument, combined with the stratospheric ozone and temperature profiles from the Payerne soundings in the same period. The seasonal dependence of the differences between the results from the various instruments is greatly reduced with the application of temperature dependent absorption coefficients, with the greatest reduction obtained using the IUP data set.

The Growth-Suppressive Function of the Polycomb Group Protein Polyhomeotic Is Mediated by Polymerization of Its Sterile Alpha Motif (SAM) Domain*

PubMed Central

Robinson, Angela K.; Leal, Belinda Z.; Chadwell, Linda V.; Wang, Renjing; Ilangovan, Udayar; Kaur, Yogeet; Junco, Sarah E.; Schirf, Virgil; Osmulski, Pawel A.; Gaczynska, Maria; Hinck, Andrew P.; Demeler, Borries; McEwen, Donald G.; Kim, Chongwoo A.

2012-01-01

Polyhomeotic (Ph), a member of the Polycomb Group (PcG), is a gene silencer critical for proper development. We present a previously unrecognized way of controlling Ph function through modulation of its sterile alpha motif (SAM) polymerization leading to the identification of a novel target for tuning the activities of proteins. SAM domain containing proteins have been shown to require SAM polymerization for proper function. However, the role of the Ph SAM polymer in PcG-mediated gene silencing was uncertain. Here, we first show that Ph SAM polymerization is indeed required for its gene silencing function. Interestingly, the unstructured linker sequence N-terminal to Ph SAM can shorten the length of polymers compared with when Ph SAM is individually isolated. Substituting the native linker with a random, unstructured sequence (RLink) can still limit polymerization, but not as well as the native linker. Consequently, the increased polymeric Ph RLink exhibits better gene silencing ability. In the Drosophila wing disc, Ph RLink expression suppresses growth compared with no effect for wild-type Ph, and opposite to the overgrowth phenotype observed for polymer-deficient Ph mutants. These data provide the first demonstration that the inherent activity of a protein containing a polymeric SAM can be enhanced by increasing SAM polymerization. Because the SAM linker had not been previously considered important for the function of SAM-containing proteins, our finding opens numerous opportunities to manipulate linker sequences of hundreds of polymeric SAM proteins to regulate a diverse array of intracellular functions. PMID:22275371

The C-terminal region of translesion synthesis DNA polymerase η is partially unstructured and has high conformational flexibility

PubMed Central

Powers, Kyle T; Washington, M Todd

2018-01-01

Abstract Eukaryotic DNA polymerase η catalyzes translesion synthesis of thymine dimers and 8-oxoguanines. It is comprised of a polymerase domain and a C-terminal region, both of which are required for its biological function. The C-terminal region mediates interactions with proliferating cell nuclear antigen (PCNA) and other translesion synthesis proteins such as Rev1. This region contains a ubiquitin-binding/zinc-binding (UBZ) motif and a PCNA-interacting protein (PIP) motif. Currently little structural information is available for this region of polymerase η. Using a combination of approaches—including genetic complementation assays, X-ray crystallography, Langevin dynamics simulations, and small-angle X-ray scattering—we show that the C-terminal region is partially unstructured and has high conformational flexibility. This implies that the C-terminal region acts as a flexible tether linking the polymerase domain to PCNA thereby increasing its local concentration. Such tethering would facilitate the sampling of translesion synthesis polymerases to ensure that the most appropriate one is selected to bypass the lesion. PMID:29385534

Intrauterine Pressure (IUP) Telemetry in Pregnant and Parturient Rats: Potential Applications for Spacecraft and Centrifugation Studies

NASA Technical Reports Server (NTRS)

Ronca, A. E.; Baer, L. A.; Wade, C. E.

2003-01-01

Rats exposed to spaceflight or centrifugation from mid-to late pregnancy undergo either more or fewer labor contractions at birth, respectively, as compared to those in normal Earth gravity (1-g). In this paper, we report the development and validation of a new telemetric method for quantifying intrauterine pressure (IUP) in freely-moving, late pregnant and parturient rats. We plan to utilize this technique for studies of labor in altered gravity, specifically, to ascertain forces of uterine during birth, which we believe may be changed in micro- and hypergravity. The technique we describe yields precise, reliable measures of the forces experienced by rat fetuses during parturition. A small, surgically-implantable telemetric pressure sensor was fitted within a fluid-filled balloon. The total volume of the sensor-balloon assembly matched that of a full term rat fetus. Real-time videorecordings of sensor-implanted rat dams and non- implanted control dams enabled us to characterize effects of the intrauterine implant on behavioral aspects of parturition. Contraction frequency, duration, pup-to-pup birth intervals and pup-oriented activities of the dams measured during the peri-birth period were unaffected by the sensor implant. These findings establish intrauterine telemetry as a reliable, non-invasive technique for quantifying intrauterine pressures associated with parturition on Earth and in altered gravity environments. This new technology, readily amenable to spaceflight and centrifugation platforms, will enable us to answer key questions regarding the role of altered labor frequency labor in the adaptation of newborn mammals to hypo- and hypergravity.

Prospects and expectations for unstructured methods

NASA Technical Reports Server (NTRS)

Baker, Timothy J.

1995-01-01

The last decade has witnessed a vigorous and sustained research effort on unstructured methods for computational fluid dynamics. Unstructured mesh generators and flow solvers have evolved to the point where they are now in use for design purposes throughout the aerospace industry. In this paper we survey the various mesh types, structured as well as unstructured, and examine their relative strengths and weaknesses. We argue that unstructured methodology does offer the best prospect for the next generation of computational fluid dynamics algorithms.

Generation of unstructured grids and Euler solutions for complex geometries

NASA Technical Reports Server (NTRS)

Loehner, Rainald; Parikh, Paresh; Salas, Manuel D.

1989-01-01

Algorithms are described for the generation and adaptation of unstructured grids in two and three dimensions, as well as Euler solvers for unstructured grids. The main purpose is to demonstrate how unstructured grids may be employed advantageously for the economic simulation of both geometrically as well as physically complex flow fields.

Location of Dual Sites in E. coli FtsZ Important for Degradation by ClpXP; One at the C-Terminus and One in the Disordered Linker

PubMed Central

Camberg, Jodi L.; Viola, Marissa G.; Rea, Leslie; Hoskins, Joel R.; Wickner, Sue

2014-01-01

ClpXP is a two-component ATP-dependent protease that unfolds and degrades proteins bearing specific recognition signals. One substrate degraded by Escherichia coli ClpXP is FtsZ, an essential cell division protein. FtsZ forms polymers that assemble into a large ring-like structure, termed the Z-ring, during cell division at the site of constriction. The FtsZ monomer is composed of an N-terminal polymerization domain, an unstructured linker region and a C-terminal conserved region. To better understand substrate selection by ClpXP, we engineered FtsZ mutant proteins containing amino acid substitutions or deletions near the FtsZ C-terminus. We identified two discrete regions of FtsZ important for degradation of both FtsZ monomers and polymers by ClpXP in vitro. One region is located 30 residues away from the C-terminus in the unstructured linker region that connects the polymerization domain to the C-terminal region. The other region is near the FtsZ C-terminus and partially overlaps the recognition sites for several other FtsZ-interacting proteins, including MinC, ZipA and FtsA. Mutation of either region caused the protein to be more stable and mutation of both caused an additive effect, suggesting that both regions are important. We also observed that in vitro MinC inhibits degradation of FtsZ by ClpXP, suggesting that some of the same residues in the C-terminal site that are important for degradation by ClpXP are important for binding MinC. PMID:24722340

Intrinsically disordered proteins aggregate at fungal cell-to-cell channels and regulate intercellular connectivity.

PubMed

Lai, Julian; Koh, Chuan Hock; Tjota, Monika; Pieuchot, Laurent; Raman, Vignesh; Chandrababu, Karthik Balakrishna; Yang, Daiwen; Wong, Limsoon; Jedd, Gregory

2012-09-25

Like animals and plants, multicellular fungi possess cell-to-cell channels (septal pores) that allow intercellular communication and transport. Here, using a combination of MS of Woronin body-associated proteins and a bioinformatics approach that identifies related proteins based on composition and character, we identify 17 septal pore-associated (SPA) proteins that localize to the septal pore in rings and pore-centered foci. SPA proteins are not homologous at the primary sequence level but share overall physical properties with intrinsically disordered proteins. Some SPA proteins form aggregates at the septal pore, and in vitro assembly assays suggest aggregation through a nonamyloidal mechanism involving mainly α-helical and disordered structures. SPA loss-of-function phenotypes include excessive septation, septal pore degeneration, and uncontrolled Woronin body activation. Together, our data identify the septal pore as a complex subcellular compartment and focal point for the assembly of unstructured proteins controlling diverse aspects of intercellular connectivity.

A multipurpose fusion tag derived from an unstructured and hyperacidic region of the amyloid precursor protein

PubMed Central

Sangawa, Takeshi; Tabata, Sanae; Suzuki, Kei; Saheki, Yasushi; Tanaka, Keiji; Takagi, Junichi

2013-01-01

Expression and purification of aggregation-prone and disulfide-containing proteins in Escherichia coli remains as a major hurdle for structural and functional analyses of high-value target proteins. Here, we present a novel gene-fusion strategy that greatly simplifies purification and refolding procedure at very low cost using a unique hyperacidic module derived from the human amyloid precursor protein. Fusion with this polypeptide (dubbed FATT for Flag-Acidic-Target Tag) results in near-complete soluble expression of variety of extracellular proteins, which can be directly refolded in the crude bacterial lysate and purified in one-step by anion exchange chromatography. Application of this system enabled preparation of functionally active extracellular enzymes and antibody fragments without the need for condition optimization. PMID:23526492

Sequence repeats and protein structure

NASA Astrophysics Data System (ADS)

Hoang, Trinh X.; Trovato, Antonio; Seno, Flavio; Banavar, Jayanth R.; Maritan, Amos

2012-11-01

Repeats are frequently found in known protein sequences. The level of sequence conservation in tandem repeats correlates with their propensities to be intrinsically disordered. We employ a coarse-grained model of a protein with a two-letter amino acid alphabet, hydrophobic (H) and polar (P), to examine the sequence-structure relationship in the realm of repeated sequences. A fraction of repeated sequences comprises a distinct class of bad folders, whose folding temperatures are much lower than those of random sequences. Imperfection in sequence repetition improves the folding properties of the bad folders while deteriorating those of the good folders. Our results may explain why nature has utilized repeated sequences for their versatility and especially to design functional proteins that are intrinsically unstructured at physiological temperatures.

Termination of pregnancy at very early gestation without visible yolk sac on ultrasound.

PubMed

Heller, Rebecca; Cameron, Sharon

2015-04-01

Requests for termination of pregnancy (TOP) at very early gestation (≤6 weeks) can prove challenging for abortion services as the ultrasound feature usually accepted as definitive evidence of an intrauterine pregnancy (IUP), the presence of a yolk sac within a gestational sac, may not yet be evident. In 2011 the Edinburgh TOP service introduced a protocol permitting women to proceed to treatment without further investigations provided that ultrasound showed the features of an eccentrically placed gestational sac (≥3 mm) with a decidual reaction, and there were no signs, symptoms or risk factors for ectopic pregnancy. A retrospective audit was conducted of outcomes of women presenting for TOP at ≤6 weeks' gestation over a 2-year period using the hospital computerised database. A total of 1155 women presented for TOP with an ultrasound gestational age of ≤6 weeks. Of these, 1030 (89%) had ultrasound evidence of a yolk sac. Eighty-seven women (7.5%) had an eccentrically placed gestational sac with a decidual reaction. All 87 women fulfilled our criteria to proceed to medical TOP, and 66 did so. In the remaining 21 cases, further investigations were performed before they proceeded to medical TOP. Two (0.17%) medical TOPs failed, both in women whose initial ultrasound had shown a yolk sac. Women with ultrasound features consistent with a very early IUP (≥3 mm eccentrically placed gestational sac with a decidual reaction) and without signs, symptoms or risk factors for ectopic pregnancy can proceed directly to medical TOP without the need for delay for further ultrasonography. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Association between knowledge about levonorgestrel emergency contraception and the risk of ectopic pregnancy following levonorgestrel emergency contraception failure: a comparative survey.

PubMed

Zhang, Duo; Yan, Ming-Xing; Ma, Jue; Xia, Wei; Xue, Rui-Hong; Sun, Jing; Zhang, Jian

2016-08-01

To study the association between knowledge about levonorgestrel emergency contraception (LNG-EC) and the risk of ectopic pregnancy (EP) following LNG-EC failure. This study included 600 women who had visited the hospital with LNG-EC failure. Of these, 300 with EP and 300 with intrauterine pregnancy (IUP) were recruited to the EP group and IUP group respectively. The participants were interviewed face-to-face using a standardized questionnaire. Pearson's chi-square tests and t-test were used to compare the sociodemographic characteristics, reproductive and gynecological history, surgical history, previous contraceptive experience, and answers to 10 questions concerning the knowledge about LNG-EC. Those who gave incorrect answers to the question regarding the basic mechanism and specific method of levonorgestrel emergency contraceptive pills (LNG-ECPs) were at a higher risk of EP after LNG-EC failure. Women who did not strictly follow instructions or advice from healthcare professionals were more likely to subsequently experience EP (p < 10(-4) ). Women with LNG-EC failure reported friends/peers, TV, and Internet as the main sources of information. No difference was observed with regard to the sources of knowledge on LNG-EC (p = 0.07). The results illustrate the importance of strictly following the doctor's guidance or drug instructions when using LNG-ECPs. The media should be used to disseminate information about responsible EC, and pharmacy staff should receive regular educational training sessions in this regard. © 2016 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd. © 2016 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.

Organized Sports and Unstructured Active Play as Physical Activity Sources in Children From Low-Income, Chicago Households.

PubMed

Appelhans, Bradley M; Li, Hong

2016-08-01

This study tested associations of organized sports participation and unstructured active play with overall moderate and vigorous physical activity (MVPA) in low-income children and examined factors associated with participation frequency. Research staff visited 88 low-income Chicago households with children ages 6-13 years. MVPA was assessed through 7-day accelerometry. Researchers documented the home availability of physical activity equipment. Caregivers reported on child participation in organized sports and unstructured active play, family support for physical activity, perceived neighborhood safety, and access to neighborhood physical activity venues. Despite similar participation in organized sports and unstructured active play, boys accumulated more MVPA than girls. MVPA was predicted by an interaction between gender and unstructured active play. Boys accumulated 23-45 additional minutes of weekday MVPA and 53-62 additional minutes of weekend MVPA through unstructured active play, with no such associations in girls. Higher reported neighborhood safety and family support for physical activity were associated with engagement in unstructured active play for both genders, and with participation in organized sports for girls. Physical activity interventions for low-income, urban children should emphasize unstructured active play, particularly in boys. Fostering family support for physical activity and safe play environments may be critical intervention components.

Control of Cellular Structural Networks Through Unstructured Protein Domains

DTIC Science & Technology

2016-07-01

stem cells (hPSCs), including embryonic and induced pluripotent stem cells . We had a third paper accepted to Scientific Reports in which we showed...2012 Stem Cells Young Investigator Award. We then had a followup paper accepted to Integrative Biology extending these ideas to human pluripotent ...morphology, mechanics, and neurogenesis in neural stem cells ; (3) To develop and use multiscale computational 1. REPORT DATE (DD-MM-YYYY) 4. TITLE AND

Implicit schemes and parallel computing in unstructured grid CFD

NASA Technical Reports Server (NTRS)

Venkatakrishnam, V.

1995-01-01

The development of implicit schemes for obtaining steady state solutions to the Euler and Navier-Stokes equations on unstructured grids is outlined. Applications are presented that compare the convergence characteristics of various implicit methods. Next, the development of explicit and implicit schemes to compute unsteady flows on unstructured grids is discussed. Next, the issues involved in parallelizing finite volume schemes on unstructured meshes in an MIMD (multiple instruction/multiple data stream) fashion are outlined. Techniques for partitioning unstructured grids among processors and for extracting parallelism in explicit and implicit solvers are discussed. Finally, some dynamic load balancing ideas, which are useful in adaptive transient computations, are presented.

Structural Insights into Membrane Targeting by the Flagellar Calcium-binding Protein (FCaBP) a Myristoylated and Palmitoylated Calcium Sensor in Trypanosoma cruzi

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

J Wingard; J Ladner; M Vanarotti

2011-12-31

The flagellar calcium-binding protein (FCaBP) of the protozoan Trypanosoma cruzi is targeted to the flagellar membrane where it regulates flagellar function and assembly. As a first step toward understanding the Ca{sup 2+}-induced conformational changes important for membrane-targeting, we report here the x-ray crystal structure of FCaBP in the Ca{sup 2+}-free state determined at 2.2{angstrom} resolution. The first 17 residues from the N terminus appear unstructured and solvent-exposed. Residues implicated in membrane targeting (Lys-19, Lys-22, and Lys-25) are flanked by an exposed N-terminal helix (residues 26-37), forming a patch of positive charge on the protein surface that may interact electrostatically withmore » flagellar membrane targets. The four EF-hands in FCaBP each adopt a 'closed conformation' similar to that seen in Ca{sup 2+}-free calmodulin. The overall fold of FCaBP is closest to that of grancalcin and other members of the penta EF-hand superfamily. Unlike the dimeric penta EF-hand proteins, FCaBP lacks a fifth EF-hand and is monomeric. The unstructured N-terminal region of FCaBP suggests that its covalently attached myristoyl group at the N terminus may be solvent-exposed, in contrast to the highly sequestered myristoyl group seen in recoverin and GCAP1. NMR analysis demonstrates that the myristoyl group attached to FCaBP is indeed solvent-exposed in both the Ca{sup 2+}-free and Ca{sup 2+}-bound states, and myristoylation has no effect on protein structure and folding stability. We propose that exposed acyl groups at the N terminus may anchor FCaBP to the flagellar membrane and that Ca{sup 2+}-induced conformational changes may control its binding to membrane-bound protein targets..« less

Direct Ubiquitin Independent Recognition and Degradation of a Folded Protein by the Eukaryotic Proteasomes-Origin of Intrinsic Degradation Signals

PubMed Central

Singh Gautam, Amit Kumar; Balakrishnan, Satish; Venkatraman, Prasanna

2012-01-01

Eukaryotic 26S proteasomes are structurally organized to recognize, unfold and degrade globular proteins. However, all existing model substrates of the 26S proteasome in addition to ubiquitin or adaptor proteins require unstructured regions in the form of fusion tags for efficient degradation. We report for the first time that purified 26S proteasome can directly recognize and degrade apomyoglobin, a globular protein, in the absence of ubiquitin, extrinsic degradation tags or adaptor proteins. Despite a high affinity interaction, absence of a ligand and presence of only helices/loops that follow the degradation signal, apomyoglobin is degraded slowly by the proteasome. A short floppy F-helix exposed upon ligand removal and in conformational equilibrium with a disordered structure is mandatory for recognition and initiation of degradation. Holomyoglobin, in which the helix is buried, is neither recognized nor degraded. Exposure of the floppy F-helix seems to sensitize the proteasome and primes the substrate for degradation. Using peptide panning and competition experiments we speculate that initial encounters through the floppy helix and additional strong interactions with N-terminal helices anchors apomyoglobin to the proteasome. Stabilizing helical structure in the floppy F-helix slows down degradation. Destabilization of adjacent helices accelerates degradation. Unfolding seems to follow the mechanism of helix unraveling rather than global unfolding. Our findings while confirming the requirement for unstructured regions in degradation offers the following new insights: a) origin and identification of an intrinsic degradation signal in the substrate, b) identification of sequences in the native substrate that are likely to be responsible for direct interactions with the proteasome, and c) identification of critical rate limiting steps like exposure of the intrinsic degron and destabilization of an unfolding intermediate that are presumably catalyzed by the ATPases. Apomyoglobin emerges as a new model substrate to further explore the role of ATPases and protein structure in proteasomal degradation PMID:22506054

Contraceptive Use and the Risk of Ectopic Pregnancy: A Multi-Center Case-Control Study.

PubMed

Li, Cheng; Zhao, Wei-Hong; Meng, Chun-Xia; Ping, Hua; Qin, Guo-Juan; Cao, Shu-Jun; Xi, Xiaowei; Zhu, Qian; Li, Xiao-Cui; Zhang, Jian

2014-01-01

To evaluate the association between the risk of ectopic pregnancy (EP) and the use of common contraceptives during the previous and current conception/menstrual cycle. A multi-center case-control study was conducted in Shanghai. Women diagnosed with EP were recruited as the case group (n = 2,411). Women with intrauterine pregnancy (IUP) (n = 2,416) and non-pregnant women (n = 2,419) were matched as controls at a ratio of 1∶1. Information regarding the previous and current use of contraceptives was collected. Multivariate logistic regression analyses were performed to calculate odds ratios (ORs) and the corresponding 95% confidential intervals (CIs). Previous use of intrauterine devices (IUDs) was associated with a slight risk of ectopic pregnancy (AOR1 = 1.87 [95% CI: 1.48-2.37]; AOR2 = 1.84 [1.49-2.27]), and the risk increased with the duration of previous use (P1 for trend <10-4, P2 for trend <10-4). The current use of most contraceptives reduced the risk of both unwanted IUP (condom: AOR = 0.04 [0.03-0.05]; withdrawal method: AOR = 0.10 [0.07-0.13]; calendar rhythm method: AOR = 0.54 [0.40-0.73]; oral contraceptive pills [OCPs]: AOR = 0.03 [0.02-0.08]; levonorgestrel emergency contraception [LNG-EC]: AOR = 0.22 [0.16-0.30]; IUDs: AOR = 0.01 [0.005-0.012]; tubal sterilization: AOR = 0.01 [0.001-0.022]) and unwanted EP (condom: AOR1 = 0.05 [0.04-0.06]; withdrawal method: AOR1 = 0.13 [0.09-0.19]; calendar rhythm method: AOR1 = 0.66 [0.48-0.91]; OCPs: AOR1 = 0.14 [0.07-0.26]; IUDs: AOR1 = 0.17 [0.13-0.22]; tubal sterilization: AOR1 = 0.04 [0.02-0.08]). However, when contraception failed and pregnancy occurred, current use of OCPs (AOR2 = 4.06 [1.64-10.07]), LNG-EC (AOR2 = 4.87 [3.88-6.10]), IUDs (AOR2 = 21.08 [13.44-33.07]), and tubal sterilization (AOR2 = 7.68 [1.69-34.80]) increased the risk of EP compared with the non-use of contraceptives. Current use of most contraceptives reduce the risk of both IUP and EP. However, if the contraceptive method fails, the proportions of EP may be higher than those of non-users. In the case of contraceptive failure in the current cycle, EP cases should be differentiated according to current use of OCPs, LNG-EC, IUDs, and tubal sterilization. In addition, attention should be paid to women with previous long-term use of IUDs.

The Feasibility of Adaptive Unstructured Computations On Petaflops Systems

NASA Technical Reports Server (NTRS)

Biswas, Rupak; Oliker, Leonid; Heber, Gerd; Gao, Guang; Saini, Subhash (Technical Monitor)

1999-01-01

This viewgraph presentation covers the advantages of mesh adaptation, unstructured grids, and dynamic load balancing. It illustrates parallel adaptive communications, and explains PLUM (Parallel dynamic load balancing for adaptive unstructured meshes), and PSAW (Proper Self Avoiding Walks).

Best Practices for Unstructured Grid Shock-Fitting

NASA Technical Reports Server (NTRS)

McCoud, Peter L.

2017-01-01

Unstructured grid solvers have well-known issues predicting surface heat fluxes when strong shocks are present. Various efforts have been made to address the underlying numerical issues that cause the erroneous predictions. The present work addresses some of the shortcomings of unstructured grid solvers, not by addressing the numerics, but by applying structured grid best practices to unstructured grids. A methodology for robust shock detection and shock-fitting is outlined and applied to production-relevant cases. Results

Adaption of unstructured meshes using node movement

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

Carpenter, J.G.; McRae, V.D.S.

1996-12-31

The adaption algorithm of Benson and McRae is modified for application to unstructured grids. The weight function generation was modified for application to unstructured grids and movement was limited to prevent cross over. A NACA 0012 airfoil is used as a test case to evaluate the modified algorithm when applied to unstructured grids and compared to results obtained by Warren. An adaptive mesh solution for the Sudhoo and Hall four element airfoil is included as a demonstration case.

Intrinsically disordered proteins aggregate at fungal cell-to-cell channels and regulate intercellular connectivity

PubMed Central

Lai, Julian; Koh, Chuan Hock; Tjota, Monika; Pieuchot, Laurent; Raman, Vignesh; Chandrababu, Karthik Balakrishna; Yang, Daiwen; Wong, Limsoon; Jedd, Gregory

2012-01-01

Like animals and plants, multicellular fungi possess cell-to-cell channels (septal pores) that allow intercellular communication and transport. Here, using a combination of MS of Woronin body-associated proteins and a bioinformatics approach that identifies related proteins based on composition and character, we identify 17 septal pore-associated (SPA) proteins that localize to the septal pore in rings and pore-centered foci. SPA proteins are not homologous at the primary sequence level but share overall physical properties with intrinsically disordered proteins. Some SPA proteins form aggregates at the septal pore, and in vitro assembly assays suggest aggregation through a nonamyloidal mechanism involving mainly α-helical and disordered structures. SPA loss-of-function phenotypes include excessive septation, septal pore degeneration, and uncontrolled Woronin body activation. Together, our data identify the septal pore as a complex subcellular compartment and focal point for the assembly of unstructured proteins controlling diverse aspects of intercellular connectivity. PMID:22955885

In-cell NMR reveals potential precursor of toxic species from SOD1 fALS mutants

NASA Astrophysics Data System (ADS)

Luchinat, Enrico; Barbieri, Letizia; Rubino, Jeffrey T.; Kozyreva, Tatiana; Cantini, Francesca; Banci, Lucia

2014-11-01

Mutations in the superoxide dismutase 1 (SOD1) gene are related to familial cases of amyotrophic lateral sclerosis (fALS). Here we exploit in-cell NMR to characterize the protein folding and maturation of a series of fALS-linked SOD1 mutants in human cells and to obtain insight into their behaviour in the cellular context, at the molecular level. The effect of various mutations on SOD1 maturation are investigated by changing the availability of metal ions in the cells, and by coexpressing the copper chaperone for SOD1, hCCS. We observe for most of the mutants the occurrence of an unstructured SOD1 species, unable to bind zinc. This species may be a common precursor of potentially toxic oligomeric species, that are associated with fALS. Coexpression of hCCS in the presence of copper restores the correct maturation of the SOD1 mutants and prevents the formation of the unstructured species, confirming that hCCS also acts as a molecular chaperone.

Extreme disorder in an ultrahigh-affinity protein complex

NASA Astrophysics Data System (ADS)

Borgia, Alessandro; Borgia, Madeleine B.; Bugge, Katrine; Kissling, Vera M.; Heidarsson, Pétur O.; Fernandes, Catarina B.; Sottini, Andrea; Soranno, Andrea; Buholzer, Karin J.; Nettels, Daniel; Kragelund, Birthe B.; Best, Robert B.; Schuler, Benjamin

2018-03-01

Molecular communication in biology is mediated by protein interactions. According to the current paradigm, the specificity and affinity required for these interactions are encoded in the precise complementarity of binding interfaces. Even proteins that are disordered under physiological conditions or that contain large unstructured regions commonly interact with well-structured binding sites on other biomolecules. Here we demonstrate the existence of an unexpected interaction mechanism: the two intrinsically disordered human proteins histone H1 and its nuclear chaperone prothymosin-α associate in a complex with picomolar affinity, but fully retain their structural disorder, long-range flexibility and highly dynamic character. On the basis of closely integrated experiments and molecular simulations, we show that the interaction can be explained by the large opposite net charge of the two proteins, without requiring defined binding sites or interactions between specific individual residues. Proteome-wide sequence analysis suggests that this interaction mechanism may be abundant in eukaryotes.

Enhanced Wang Landau sampling of adsorbed protein conformations.

PubMed

Radhakrishna, Mithun; Sharma, Sumit; Kumar, Sanat K

2012-03-21

Using computer simulations to model the folding of proteins into their native states is computationally expensive due to the extraordinarily low degeneracy of the ground state. In this paper, we develop an efficient way to sample these folded conformations using Wang Landau sampling coupled with the configurational bias method (which uses an unphysical "temperature" that lies between the collapse and folding transition temperatures of the protein). This method speeds up the folding process by roughly an order of magnitude over existing algorithms for the sequences studied. We apply this method to study the adsorption of intrinsically disordered hydrophobic polar protein fragments on a hydrophobic surface. We find that these fragments, which are unstructured in the bulk, acquire secondary structure upon adsorption onto a strong hydrophobic surface. Apparently, the presence of a hydrophobic surface allows these random coil fragments to fold by providing hydrophobic contacts that were lost in protein fragmentation. © 2012 American Institute of Physics

Intrinsically disordered proteins--relation to general model expressing the active role of the water environment.

PubMed

Kalinowska, Barbara; Banach, Mateusz; Konieczny, Leszek; Marchewka, Damian; Roterman, Irena

2014-01-01

This work discusses the role of unstructured polypeptide chain fragments in shaping the protein's hydrophobic core. Based on the "fuzzy oil drop" model, which assumes an idealized distribution of hydrophobicity density described by the 3D Gaussian, we can determine which fragments make up the core and pinpoint residues whose location conflicts with theoretical predictions. We show that the structural influence of the water environment determines the positions of disordered fragments, leading to the formation of a hydrophobic core overlaid by a hydrophilic mantle. This phenomenon is further described by studying selected proteins which are known to be unstable and contain intrinsically disordered fragments. Their properties are established quantitatively, explaining the causative relation between the protein's structure and function and facilitating further comparative analyses of various structural models. © 2014 Elsevier Inc. All rights reserved.

Overcoming the Challenges of Unstructured Data in Multisite, Electronic Medical Record-based Abstraction.

PubMed

Polnaszek, Brock; Gilmore-Bykovskyi, Andrea; Hovanes, Melissa; Roiland, Rachel; Ferguson, Patrick; Brown, Roger; Kind, Amy J H

2016-10-01

Unstructured data encountered during retrospective electronic medical record (EMR) abstraction has routinely been identified as challenging to reliably abstract, as these data are often recorded as free text, without limitations to format or structure. There is increased interest in reliably abstracting this type of data given its prominent role in care coordination and communication, yet limited methodological guidance exists. As standard abstraction approaches resulted in substandard data reliability for unstructured data elements collected as part of a multisite, retrospective EMR study of hospital discharge communication quality, our goal was to develop, apply and examine the utility of a phase-based approach to reliably abstract unstructured data. This approach is examined using the specific example of discharge communication for warfarin management. We adopted a "fit-for-use" framework to guide the development and evaluation of abstraction methods using a 4-step, phase-based approach including (1) team building; (2) identification of challenges; (3) adaptation of abstraction methods; and (4) systematic data quality monitoring. Unstructured data elements were the focus of this study, including elements communicating steps in warfarin management (eg, warfarin initiation) and medical follow-up (eg, timeframe for follow-up). After implementation of the phase-based approach, interrater reliability for all unstructured data elements demonstrated κ's of ≥0.89-an average increase of +0.25 for each unstructured data element. As compared with standard abstraction methodologies, this phase-based approach was more time intensive, but did markedly increase abstraction reliability for unstructured data elements within multisite EMR documentation.

The ClusPro web server for protein-protein docking

PubMed Central

Kozakov, Dima; Hall, David R.; Xia, Bing; Porter, Kathryn A.; Padhorny, Dzmitry; Yueh, Christine; Beglov, Dmitri; Vajda, Sandor

2017-01-01

The ClusPro server (https://cluspro.org) is a widely used tool for protein-protein docking. The server provides a simple home page for basic use, requiring only two files in Protein Data Bank format. However, ClusPro also offers a number of advanced options to modify the search that include the removal of unstructured protein regions, applying attraction or repulsion, accounting for pairwise distance restraints, constructing homo-multimers, considering small angle X-ray scattering (SAXS) data, and finding heparin binding sites. Six different energy functions can be used depending on the type of proteins. Docking with each energy parameter set results in ten models defined by centers of highly populated clusters of low energy docked structures. This protocol describes the use of the various options, the construction of auxiliary restraints files, the selection of the energy parameters, and the analysis of the results. Although the server is heavily used, runs are generally completed in < 4 hours. PMID:28079879

Solution structure and interactions of the Escherichia coli cell division activator protein CedA.

PubMed

Chen, Ho An; Simpson, Peter; Huyton, Trevor; Roper, David; Matthews, Stephen

2005-05-10

CedA is a protein that is postulated to be involved in the regulation of cell division in Escherichia coli and related organisms; however, little biological data about its possible mode of action are available. Here we present a three-dimensional structure of this protein as determined by NMR spectroscopy. The protein is made up of four antiparallel beta-strands, an alpha-helix, and a large unstructured stretch of residues at the N-terminus. It shows structural similarity to a family of DNA-binding proteins which interact with dsDNA via a three-stranded beta-sheet, suggesting that CedA may be a DNA-binding protein. The putative binding surface of CedA is predominantly positively charged with a number of basic residues surrounding a groove largely dominated by aromatic residues. NMR chemical shift perturbations and gel-shift experiments performed with CedA confirm that the protein binds dsDNA, and its interaction is mediated primarily via the beta-sheet.

Integrated Bio-Entity Network: A System for Biological Knowledge Discovery

PubMed Central

Bell, Lindsey; Chowdhary, Rajesh; Liu, Jun S.; Niu, Xufeng; Zhang, Jinfeng

2011-01-01

A significant part of our biological knowledge is centered on relationships between biological entities (bio-entities) such as proteins, genes, small molecules, pathways, gene ontology (GO) terms and diseases. Accumulated at an increasing speed, the information on bio-entity relationships is archived in different forms at scattered places. Most of such information is buried in scientific literature as unstructured text. Organizing heterogeneous information in a structured form not only facilitates study of biological systems using integrative approaches, but also allows discovery of new knowledge in an automatic and systematic way. In this study, we performed a large scale integration of bio-entity relationship information from both databases containing manually annotated, structured information and automatic information extraction of unstructured text in scientific literature. The relationship information we integrated in this study includes protein–protein interactions, protein/gene regulations, protein–small molecule interactions, protein–GO relationships, protein–pathway relationships, and pathway–disease relationships. The relationship information is organized in a graph data structure, named integrated bio-entity network (IBN), where the vertices are the bio-entities and edges represent their relationships. Under this framework, graph theoretic algorithms can be designed to perform various knowledge discovery tasks. We designed breadth-first search with pruning (BFSP) and most probable path (MPP) algorithms to automatically generate hypotheses—the indirect relationships with high probabilities in the network. We show that IBN can be used to generate plausible hypotheses, which not only help to better understand the complex interactions in biological systems, but also provide guidance for experimental designs. PMID:21738677

Best Practices for Unstructured Grid Shock Fitting

NASA Technical Reports Server (NTRS)

McCloud, Peter L.

2017-01-01

Unstructured grid solvers have well-known issues predicting surface heat fluxes when strong shocks are present. Various efforts have been made to address the underlying numerical issues that cause the erroneous predictions. The present work addresses some of the shortcomings of unstructured grid solvers, not by addressing the numerics, but by applying structured grid best practices to unstructured grids. A methodology for robust shock detection and shock fitting is outlined and applied to production relevant cases. Results achieved by using the Loci-CHEM Computational Fluid Dynamics solver are provided.

Aspects of Unstructured Grids and Finite-Volume Solvers for the Euler and Navier-Stokes Equations

NASA Technical Reports Server (NTRS)

Barth, Timothy J.

1992-01-01

One of the major achievements in engineering science has been the development of computer algorithms for solving nonlinear differential equations such as the Navier-Stokes equations. In the past, limited computer resources have motivated the development of efficient numerical schemes in computational fluid dynamics (CFD) utilizing structured meshes. The use of structured meshes greatly simplifies the implementation of CFD algorithms on conventional computers. Unstructured grids on the other hand offer an alternative to modeling complex geometries. Unstructured meshes have irregular connectivity and usually contain combinations of triangles, quadrilaterals, tetrahedra, and hexahedra. The generation and use of unstructured grids poses new challenges in CFD. The purpose of this note is to present recent developments in the unstructured grid generation and flow solution technology.

Development of a Regional Structured and Unstructured Grid Methodology for Chemically Reactive Turbulent Flows

NASA Astrophysics Data System (ADS)

Stefanski, Douglas Lawrence

A finite volume method for solving the Reynolds Averaged Navier-Stokes (RANS) equations on unstructured hybrid grids is presented. Capabilities for handling arbitrary mixtures of reactive gas species within the unstructured framework are developed. The modeling of turbulent effects is carried out via the 1998 Wilcox k -- o model. This unstructured solver is incorporated within VULCAN -- a multi-block structured grid code -- as part of a novel patching procedure in which non-matching interfaces between structured blocks are replaced by transitional unstructured grids. This approach provides a fully-conservative alternative to VULCAN's non-conservative patching methods for handling such interfaces. In addition, the further development of the standalone unstructured solver toward large-eddy simulation (LES) applications is also carried out. Dual time-stepping using a Crank-Nicholson formulation is added to recover time-accuracy, and modeling of sub-grid scale effects is incorporated to provide higher fidelity LES solutions for turbulent flows. A switch based on the work of Ducros, et al., is implemented to transition from a monotonicity-preserving flux scheme near shocks to a central-difference method in vorticity-dominated regions in order to better resolve small-scale turbulent structures. The updated unstructured solver is used to carry out large-eddy simulations of a supersonic constrained mixing layer.

Empirical Correction for Differences in Chemical Exchange Rates in Hydrogen Exchange-Mass Spectrometry Measurements.

PubMed

Toth, Ronald T; Mills, Brittney J; Joshi, Sangeeta B; Esfandiary, Reza; Bishop, Steven M; Middaugh, C Russell; Volkin, David B; Weis, David D

2017-09-05

A barrier to the use of hydrogen exchange-mass spectrometry (HX-MS) in many contexts, especially analytical characterization of various protein therapeutic candidates, is that differences in temperature, pH, ionic strength, buffering agent, or other additives can alter chemical exchange rates, making HX data gathered under differing solution conditions difficult to compare. Here, we present data demonstrating that HX chemical exchange rates can be substantially altered not only by the well-established variables of temperature and pH but also by additives including arginine, guanidine, methionine, and thiocyanate. To compensate for these additive effects, we have developed an empirical method to correct the hydrogen-exchange data for these differences. First, differences in chemical exchange rates are measured by use of an unstructured reporter peptide, YPI. An empirical chemical exchange correction factor, determined by use of the HX data from the reporter peptide, is then applied to the HX measurements obtained from a protein of interest under different solution conditions. We demonstrate that the correction is experimentally sound through simulation and in a proof-of-concept experiment using unstructured peptides under slow-exchange conditions (pD 4.5 at ambient temperature). To illustrate its utility, we applied the correction to HX-MS excipient screening data collected for a pharmaceutically relevant IgG4 mAb being characterized to determine the effects of different formulations on backbone dynamics.

Structure based aggregation studies reveal the presence of helix-rich intermediate during α-Synuclein aggregation

PubMed Central

Ghosh, Dhiman; Singh, Pradeep K.; Sahay, Shruti; Jha, Narendra Nath; Jacob, Reeba S.; Sen, Shamik; Kumar, Ashutosh; Riek, Roland; Maji, Samir K.

2015-01-01

Mechanistic understanding of nucleation dependent polymerization by α-synuclein (α-Syn) into toxic oligomers and amyloids is important for the drug development against Parkinson's disease. However the structural and morphological characterization during nucleation and subsequent fibrillation process of α-Syn is not clearly understood. Using a variety of complementary biophysical techniques monitoring entire pathway of nine different synucleins, we found that transition of unstructured conformation into β-sheet rich fibril formation involves helix-rich intermediates. These intermediates are common for all aggregating synucleins, contain high solvent-exposed hydrophobic surfaces, are cytotoxic to SHSY-5Y cells and accelerate α-Syn aggregation efficiently. A multidimensional NMR study characterizing the intermediate accompanied with site-specific fluorescence study suggests that the N-terminal and central portions mainly participate in the helix-rich intermediate formation while the C-terminus remained in an extended conformation. However, significant conformational transitions occur at the middle and at the C-terminus during helix to β-sheet transition as evident from Trp fluorescence study. Since partial helix-rich intermediates were also observed for other amyloidogenic proteins such as Aβ and IAPP, we hypothesize that this class of intermediates may be one of the important intermediates for amyloid formation pathway by many natively unstructured protein/peptides and represent a potential target for drug development against amyloid diseases. PMID:25784353

Overcoming the Challenges of Unstructured Data in Multi-site, Electronic Medical Record-based Abstraction

PubMed Central

Polnaszek, Brock; Gilmore-Bykovskyi, Andrea; Hovanes, Melissa; Roiland, Rachel; Ferguson, Patrick; Brown, Roger; Kind, Amy JH

2014-01-01

Background Unstructured data encountered during retrospective electronic medical record (EMR) abstraction has routinely been identified as challenging to reliably abstract, as this data is often recorded as free text, without limitations to format or structure. There is increased interest in reliably abstracting this type of data given its prominent role in care coordination and communication, yet limited methodological guidance exists. Objective As standard abstraction approaches resulted in sub-standard data reliability for unstructured data elements collected as part of a multi-site, retrospective EMR study of hospital discharge communication quality, our goal was to develop, apply and examine the utility of a phase-based approach to reliably abstract unstructured data. This approach is examined using the specific example of discharge communication for warfarin management. Research Design We adopted a “fit-for-use” framework to guide the development and evaluation of abstraction methods using a four step, phase-based approach including (1) team building, (2) identification of challenges, (3) adaptation of abstraction methods, and (4) systematic data quality monitoring. Measures Unstructured data elements were the focus of this study, including elements communicating steps in warfarin management (e.g., warfarin initiation) and medical follow-up (e.g., timeframe for follow-up). Results After implementation of the phase-based approach, inter-rater reliability for all unstructured data elements demonstrated kappas of ≥ 0.89 -- an average increase of + 0.25 for each unstructured data element. Conclusions As compared to standard abstraction methodologies, this phase-based approach was more time intensive, but did markedly increase abstraction reliability for unstructured data elements within multi-site EMR documentation. PMID:27624585

An assessment of unstructured grid technology for timely CFD analysis

NASA Technical Reports Server (NTRS)

Kinard, Tom A.; Schabowski, Deanne M.

1995-01-01

An assessment of two unstructured methods is presented in this paper. A tetrahedral unstructured method USM3D, developed at NASA Langley Research Center is compared to a Cartesian unstructured method, SPLITFLOW, developed at Lockheed Fort Worth Company. USM3D is an upwind finite volume solver that accepts grids generated primarily from the Vgrid grid generator. SPLITFLOW combines an unstructured grid generator with an implicit flow solver in one package. Both methods are exercised on three test cases, a wing, and a wing body, and a fully expanded nozzle. The results for the first two runs are included here and compared to the structured grid method TEAM and to available test data. On each test case, the set up procedure are described, including any difficulties that were encountered. Detailed descriptions of the solvers are not included in this paper.

Comparative Reliability of Structured Versus Unstructured Interviews in the Admission Process of a Residency Program

PubMed Central

Blouin, Danielle; Day, Andrew G.; Pavlov, Andrey

2011-01-01

Background Although never directly compared, structured interviews are reported as being more reliable than unstructured interviews. This study compared the reliability of both types of interview when applied to a common pool of applicants for positions in an emergency medicine residency program. Methods In 2008, one structured interview was added to the two unstructured interviews traditionally used in our resident selection process. A formal job analysis using the critical incident technique guided the development of the structured interview tool. This tool consisted of 7 scenarios assessing 4 of the domains deemed essential for success as a resident in this program. The traditional interview tool assessed 5 general criteria. In addition to these criteria, the unstructured panel members were asked to rate each candidate on the same 4 essential domains rated by the structured panel members. All 3 panels interviewed all candidates. Main outcomes were the overall, interitem, and interrater reliabilities, the correlations between interview panels, and the dimensionality of each interview tool. Results Thirty candidates were interviewed. The overall reliability reached 0.43 for the structured interview, and 0.81 and 0.71 for the unstructured interviews. Analyses of the variance components showed a high interrater, low interitem reliability for the structured interview, and a high interrater, high interitem reliability for the unstructured interviews. The summary measures from the 2 unstructured interviews were significantly correlated, but neither was correlated with the structured interview. Only the structured interview was multidimensional. Conclusions A structured interview did not yield a higher overall reliability than both unstructured interviews. The lower reliability is explained by a lower interitem reliability, which in turn is due to the multidimensionality of the interview tool. Both unstructured panels consistently rated a single dimension, even when prompted to assess the 4 specific domains established as essential to succeed in this residency program. PMID:23205201

Comparative reliability of structured versus unstructured interviews in the admission process of a residency program.

PubMed

Blouin, Danielle; Day, Andrew G; Pavlov, Andrey

2011-12-01

Although never directly compared, structured interviews are reported as being more reliable than unstructured interviews. This study compared the reliability of both types of interview when applied to a common pool of applicants for positions in an emergency medicine residency program. In 2008, one structured interview was added to the two unstructured interviews traditionally used in our resident selection process. A formal job analysis using the critical incident technique guided the development of the structured interview tool. This tool consisted of 7 scenarios assessing 4 of the domains deemed essential for success as a resident in this program. The traditional interview tool assessed 5 general criteria. In addition to these criteria, the unstructured panel members were asked to rate each candidate on the same 4 essential domains rated by the structured panel members. All 3 panels interviewed all candidates. Main outcomes were the overall, interitem, and interrater reliabilities, the correlations between interview panels, and the dimensionality of each interview tool. Thirty candidates were interviewed. The overall reliability reached 0.43 for the structured interview, and 0.81 and 0.71 for the unstructured interviews. Analyses of the variance components showed a high interrater, low interitem reliability for the structured interview, and a high interrater, high interitem reliability for the unstructured interviews. The summary measures from the 2 unstructured interviews were significantly correlated, but neither was correlated with the structured interview. Only the structured interview was multidimensional. A structured interview did not yield a higher overall reliability than both unstructured interviews. The lower reliability is explained by a lower interitem reliability, which in turn is due to the multidimensionality of the interview tool. Both unstructured panels consistently rated a single dimension, even when prompted to assess the 4 specific domains established as essential to succeed in this residency program.

Interferences of Silica Nanoparticles in Green Fluorescent Protein Folding Processes.

PubMed

Klein, Géraldine; Devineau, Stéphanie; Aude, Jean Christophe; Boulard, Yves; Pasquier, Hélène; Labarre, Jean; Pin, Serge; Renault, Jean Philippe

2016-01-12

We investigated the relationship between unfolded proteins, silica nanoparticles and chaperonin to determine whether unfolded proteins could stick to silica surfaces and how this process could impair heat shock protein activity. The HSP60 catalyzed green fluorescent protein (GFP) folding was used as a model system. The adsorption isotherms and adsorption kinetics of denatured GFP were measured, showing that denaturation increases GFP affinity for silica surfaces. This affinity is maintained even if the surfaces are covered by a protein corona and allows silica NPs to interfere directly with GFP folding by trapping it in its unstructured state. We determined also the adsorption isotherms of HSP60 and its chaperonin activity once adsorbed, showing that SiO2 NP can interfere also indirectly with protein folding through chaperonin trapping and inhibition. This inhibition is specifically efficient when NPs are covered first with a layer of unfolded proteins. These results highlight for the first time the antichaperonin activity of silica NPs and ask new questions about the toxicity of such misfolded proteins/nanoparticles assembly toward cells.

Multigrid techniques for unstructured meshes

NASA Technical Reports Server (NTRS)

Mavriplis, D. J.

1995-01-01

An overview of current multigrid techniques for unstructured meshes is given. The basic principles of the multigrid approach are first outlined. Application of these principles to unstructured mesh problems is then described, illustrating various different approaches, and giving examples of practical applications. Advanced multigrid topics, such as the use of algebraic multigrid methods, and the combination of multigrid techniques with adaptive meshing strategies are dealt with in subsequent sections. These represent current areas of research, and the unresolved issues are discussed. The presentation is organized in an educational manner, for readers familiar with computational fluid dynamics, wishing to learn more about current unstructured mesh techniques.

Unstructured Euler flow solutions using hexahedral cell refinement

NASA Technical Reports Server (NTRS)

Melton, John E.; Cappuccio, Gelsomina; Thomas, Scott D.

1991-01-01

An attempt is made to extend grid refinement into three dimensions by using unstructured hexahedral grids. The flow solver is developed using the TIGER (topologically Independent Grid, Euler Refinement) as the starting point. The program uses an unstructured hexahedral mesh and a modified version of the Jameson four-stage, finite-volume Runge-Kutta algorithm for integration of the Euler equations. The unstructured mesh allows for local refinement appropriate for each freestream condition, thereby concentrating mesh cells in the regions of greatest interest. This increases the computational efficiency because the refinement is not required to extend throughout the entire flow field.

From protein interaction profile to functional assignment: the human protein Ki-1/57 is associated with pre-mRNA splicing events.

PubMed

Bressan, Gustavo Costa; Kobarg, Jörg

2010-01-01

The mapping of protein-protein interactions of a determined organism is considered fundamental to assign protein function in the post-genomic era. As part of this effort, screenings for pairwise interactions by yeast two-hybrid system have been used popularly to reveal protein interaction networks in different biological systems. Through the identification of protein interaction partners we have successfully obtained interesting functional clues for Ki-1/57, a human protein with no previous functional annotation, in the context of RNA metabolism. We briefly discuss the way we approached protein-protein interaction data to conduct and interpret further molecular biological and cellular studies as well as structural analyses on this protein. Our data suggest that Ki-1/57 belongs to the family of intrinsically unstructured proteins and that the structural flexibility may be crucial for its capacity to interact with many different proteins. A large fraction of these proteins are involved in pre-mRNA splicing control. Finally, Ki-1/57 is localized to several subnuclear domains, all of which have been described to splicing and other RNA processing events.

SIRAH: a structurally unbiased coarse-grained force field for proteins with aqueous solvation and long-range electrostatics.

PubMed

Darré, Leonardo; Machado, Matías Rodrigo; Brandner, Astrid Febe; González, Humberto Carlos; Ferreira, Sebastián; Pantano, Sergio

2015-02-10

Modeling of macromolecular structures and interactions represents an important challenge for computational biology, involving different time and length scales. However, this task can be facilitated through the use of coarse-grained (CG) models, which reduce the number of degrees of freedom and allow efficient exploration of complex conformational spaces. This article presents a new CG protein model named SIRAH, developed to work with explicit solvent and to capture sequence, temperature, and ionic strength effects in a topologically unbiased manner. SIRAH is implemented in GROMACS, and interactions are calculated using a standard pairwise Hamiltonian for classical molecular dynamics simulations. We present a set of simulations that test the capability of SIRAH to produce a qualitatively correct solvation on different amino acids, hydrophilic/hydrophobic interactions, and long-range electrostatic recognition leading to spontaneous association of unstructured peptides and stable structures of single polypeptides and protein-protein complexes.

Organized and Unstructured Activity Participation among Adolescents Involved with Child Protective Services in the United States

ERIC Educational Resources Information Center

Kwak, Yoonyoung; Lu, Ting; Christ, Sharon L.

2017-01-01

Background: Many adolescents are referred to Child Protective Services for possible maltreatment every year, but not much is known about their organized and unstructured activity participation. Objective: The purposes of this study are to provide a description of organized and unstructured activity participation for adolescents who were possible…

Amyloidogenic Regions and Interaction Surfaces Overlap in Globular Proteins Related to Conformational Diseases

PubMed Central

Castillo, Virginia; Ventura, Salvador

2009-01-01

Protein aggregation underlies a wide range of human disorders. The polypeptides involved in these pathologies might be intrinsically unstructured or display a defined 3D-structure. Little is known about how globular proteins aggregate into toxic assemblies under physiological conditions, where they display an initially folded conformation. Protein aggregation is, however, always initiated by the establishment of anomalous protein-protein interactions. Therefore, in the present work, we have explored the extent to which protein interaction surfaces and aggregation-prone regions overlap in globular proteins associated with conformational diseases. Computational analysis of the native complexes formed by these proteins shows that aggregation-prone regions do frequently overlap with protein interfaces. The spatial coincidence of interaction sites and aggregating regions suggests that the formation of functional complexes and the aggregation of their individual subunits might compete in the cell. Accordingly, single mutations affecting complex interface or stability usually result in the formation of toxic aggregates. It is suggested that the stabilization of existing interfaces in multimeric proteins or the formation of new complexes in monomeric polypeptides might become effective strategies to prevent disease-linked aggregation of globular proteins. PMID:19696882

War Termination: Dreaming of the End and the Ultimate Triumph

DTIC Science & Technology

2004-05-17

and unstructured, art and science . To realize national strategic objectives and develop a triumphant peace, operational commanders must shun the...itself, war termination is both political and military, structured and unstructured, art and science . To realize national strategic objectives and...termination is political and military, structured and unstructured, art and science . By applying elements of operational art to war termination and

Unstructured Grid Generation Techniques and Software

NASA Technical Reports Server (NTRS)

Posenau, Mary-Anne K. (Editor)

1993-01-01

The Workshop on Unstructured Grid Generation Techniques and Software was conducted for NASA to assess its unstructured grid activities, improve the coordination among NASA centers, and promote technology transfer to industry. The proceedings represent contributions from Ames, Langley, and Lewis Research Centers, and the Johnson and Marshall Space Flight Centers. This report is a compilation of the presentations made at the workshop.

Free energy surface of an intrinsically disordered protein: comparison between temperature replica exchange molecular dynamics and bias-exchange metadynamics.

PubMed

Zerze, Gül H; Miller, Cayla M; Granata, Daniele; Mittal, Jeetain

2015-06-09

Intrinsically disordered proteins (IDPs), which are expected to be largely unstructured under physiological conditions, make up a large fraction of eukaryotic proteins. Molecular dynamics simulations have been utilized to probe structural characteristics of these proteins, which are not always easily accessible to experiments. However, exploration of the conformational space by brute force molecular dynamics simulations is often limited by short time scales. Present literature provides a number of enhanced sampling methods to explore protein conformational space in molecular simulations more efficiently. In this work, we present a comparison of two enhanced sampling methods: temperature replica exchange molecular dynamics and bias exchange metadynamics. By investigating both the free energy landscape as a function of pertinent order parameters and the per-residue secondary structures of an IDP, namely, human islet amyloid polypeptide, we found that the two methods yield similar results as expected. We also highlight the practical difference between the two methods by describing the path that we followed to obtain both sets of data.

Electrostatic Interactions and Self-Assembly in Polymeric Systems

NASA Astrophysics Data System (ADS)

Dobrynin, Andrey

Electrostatic interactions between macroions play an important role in different areas ranging from materials science to biophysics. They are main driving forces behind layer-by-layer assembly technique that allows self-assembly of multilayer films from synthetic polyelectrolytes, DNA, proteins and nanoparticles. They are responsible for complexation and reversible gelation between polyelectrolytes and proteins. In this talk, using results of the molecular dynamics simulations and analytical calculations, I will demonstrate what effect electrostatic interactions, counterion condensation and polymer solvent affinity have on a collapse of polyelectrolyte chain in a poor solvent conditions for the polymer backbone, on complexations and reversible gelation between polyelectrolytes and polyamholytes (unstructured proteins), on microphase separation transitions in spherical and planar charged brushes, and on a layer-by-layer assembly of charged nanoparticles and linear polyelectrolytes on charged surfaces. NSF DMR-1004576 DMR-1409710.

Surveying Unstructured Time of Adults with Mental Retardation Living in Two Community Settings: A Search for Normalization.

ERIC Educational Resources Information Center

Pierce, Thomas B., Jr.; And Others

1990-01-01

A survey assessed time spent in the community and/or on unstructured activities by randomly selected individuals in Intermediate Care Facilities for the Mentally Retarded (ICF/MR) (N=20) or minigroup home settings (N=20). Individuals in ICF/MR homes spent more time in the community with staff and made fewer choices of unstructured activities.…

VisualUrText: A Text Analytics Tool for Unstructured Textual Data

NASA Astrophysics Data System (ADS)

Zainol, Zuraini; Jaymes, Mohd T. H.; Nohuddin, Puteri N. E.

2018-05-01

The growing amount of unstructured text over Internet is tremendous. Text repositories come from Web 2.0, business intelligence and social networking applications. It is also believed that 80-90% of future growth data is available in the form of unstructured text databases that may potentially contain interesting patterns and trends. Text Mining is well known technique for discovering interesting patterns and trends which are non-trivial knowledge from massive unstructured text data. Text Mining covers multidisciplinary fields involving information retrieval (IR), text analysis, natural language processing (NLP), data mining, machine learning statistics and computational linguistics. This paper discusses the development of text analytics tool that is proficient in extracting, processing, analyzing the unstructured text data and visualizing cleaned text data into multiple forms such as Document Term Matrix (DTM), Frequency Graph, Network Analysis Graph, Word Cloud and Dendogram. This tool, VisualUrText, is developed to assist students and researchers for extracting interesting patterns and trends in document analyses.

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

Burke, Timothy P.; Martz, Roger L.; Kiedrowski, Brian C.

New unstructured mesh capabilities in MCNP6 (developmental version during summer 2012) show potential for conducting multi-physics analyses by coupling MCNP to a finite element solver such as Abaqus/CAE[2]. Before these new capabilities can be utilized, the ability of MCNP to accurately estimate eigenvalues and pin powers using an unstructured mesh must first be verified. Previous work to verify the unstructured mesh capabilities in MCNP was accomplished using the Godiva sphere [1], and this work attempts to build on that. To accomplish this, a criticality benchmark and a fuel assembly benchmark were used for calculations in MCNP using both the Constructivemore » Solid Geometry (CSG) native to MCNP and the unstructured mesh geometry generated using Abaqus/CAE. The Big Ten criticality benchmark [3] was modeled due to its geometry being similar to that of a reactor fuel pin. The C5G7 3-D Mixed Oxide (MOX) Fuel Assembly Benchmark [4] was modeled to test the unstructured mesh capabilities on a reactor-type problem.« less

Hybrid Solution-Adaptive Unstructured Cartesian Method for Large-Eddy Simulation of Detonation in Multi-Phase Turbulent Reactive Mixtures

DTIC Science & Technology

2012-03-27

pulse- detonation engines ( PDE ), stage separation, supersonic cav- ity oscillations, hypersonic aerodynamics, detonation induced structural...ADAPTIVE UNSTRUCTURED CARTESIAN METHOD FOR LARGE-EDDY SIMULATION OF DETONATION IN MULTI-PHASE TURBULENT REACTIVE MIXTURES 5b. GRANT NUMBER FA9550...CCL Report TR-2012-03-03 Hybrid Solution-Adaptive Unstructured Cartesian Method for Large-Eddy Simulation of Detonation in Multi-Phase Turbulent

Efficacy of the World Health Organization-recommended handwashing technique and a modified washing technique to remove Clostridium difficile from hands.

PubMed

Deschênes, Philippe; Chano, Frédéric; Dionne, Léa-Laurence; Pittet, Didier; Longtin, Yves

2017-08-01

The efficacy of the World Health Organization (WHO)-recommended handwashing technique against Clostridium difficile is uncertain, and whether it could be improved remains unknown. Also, the benefit of using a structured technique instead of an unstructured technique remains unclear. This study was a prospective comparison of 3 techniques (unstructured, WHO, and a novel technique dubbed WHO shortened repeated [WHO-SR] technique) to remove C difficile. Ten participants were enrolled and performed each technique. Hands were contaminated with 3 × 10 6 colony forming units (CFU) of a nontoxigenic strain containing 90% spores. Efficacy was assessed using the whole-hand method. The relative efficacy of each technique and of a structured (either WHO or WHO-SR) vs an unstructured technique were assessed by Mann-Whitney U test and Wilcoxon signed-rank test. The median effectiveness of the unstructured, WHO, and WHO-SR techniques in log 10 CFU reduction was 1.30 (interquartile range [IQR], 1.27-1.43), 1.71 (IQR, 1.34-1.91), and 1.70 (IQR, 1.54-2.42), respectively. The WHO-SR technique was significantly more efficacious than the unstructured technique (P = .01). Washing hands with a structured technique was more effective than washing with an unstructured technique (median, 1.70 vs 1.30 log 10 CFU reduction, respectively; P = .007). A structured washing technique is more effective than an unstructured technique against C difficile. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Entrapment of Aβ1-40 peptide in unstructured aggregates

NASA Astrophysics Data System (ADS)

Corsale, C.; Carrotta, R.; Mangione, M. R.; Vilasi, S.; Provenzano, A.; Cavallaro, G.; Bulone, D.; San Biagio, P. L.

2012-06-01

Recognizing the complexity of the fibrillogenesis process provides a solid ground for the development of therapeutic strategies aimed at preventing or inhibiting protein-protein aggregation. Under this perspective, it is meaningful to identify the possible aggregation pathways and their relative products. We found that Aβ-peptide dissolved in a pH 7.4 solution at small peptide concentration and low ionic strength forms globular aggregates without typical amyloid β-conformation. ThT binding kinetics was used to monitor aggregate formation. Circular dichroism spectroscopy, AFM imaging, static and dynamic light scattering were used for structural and morphological characterization of the aggregates. They appear stable or at least metastable with respect to fiber growth, therefore appearing as an incidental product in the pathway of fibrillogenesis.

A hybrid structured-unstructured grid method for unsteady turbomachinery flow computations

NASA Technical Reports Server (NTRS)

Mathur, Sanjay R.; Madavan, Nateri K.; Rajagopalan, R. G.

1993-01-01

A hybrid grid technique for the solution of 2D, unsteady flows is developed. This technique is capable of handling complex, multiple component geometries in relative motion, such as those encountered in turbomachinery. The numerical approach utilizes a mixed structured-unstructured zonal grid topology along with modeling equations and solution methods that are most appropriate in the individual domains, therefore combining the advantages of both structured and unstructured grid techniques.

Exploring Hypersonic, Unstructured-Grid Issues through Structured Grids

NASA Technical Reports Server (NTRS)

Mazaheri, Ali R.; Kleb, Bill

2007-01-01

Pure-tetrahedral unstructured grids have been shown to produce asymmetric heat transfer rates for symmetric problems. Meanwhile, two-dimensional structured grids produce symmetric solutions and as documented here, introducing a spanwise degree of freedom to these structured grids also yields symmetric solutions. The effects of grid skewness and other perturbations of structured-grids are investigated to uncover possible mechanisms behind the unstructured-grid solution asymmetries. By using controlled experiments around a known, good solution, the effects of particular grid pathologies are uncovered. These structured-grid experiments reveal that similar solution degradation occurs as for unstructured grids, especially for heat transfer rates. Non-smooth grids within the boundary layer is also shown to produce large local errors in heat flux but do not affect surface pressures.

Cooperative binding modes of Cu(II) in prion protein

NASA Astrophysics Data System (ADS)

Hodak, Miroslav; Chisnell, Robin; Lu, Wenchang; Bernholc, Jerry

2007-03-01

The misfolding of the prion protein, PrP, is responsible for a group of neurodegenerative diseases including mad cow disease and Creutzfeldt-Jakob disease. It is known that the PrP can efficiently bind copper ions; four high-affinity binding sites located in the octarepeat region of PrP are now well known. Recent experiments suggest that at low copper concentrations new binding modes, in which one copper ion is shared between two or more binding sites, are possible. Using our hybrid Thomas-Fermi/DFT computational scheme, which is well suited for simulations of biomolecules in solution, we investigate the geometries and energetics of two, three and four binding sites cooperatively binding one copper ion. These geometries are then used as inputs for classical molecular dynamics simulations. We find that copper binding affects the secondary structure of the PrP and that it stabilizes the unstructured (unfolded) part of the protein.

Unstructured mesh generation and adaptivity

NASA Technical Reports Server (NTRS)

Mavriplis, D. J.

1995-01-01

An overview of current unstructured mesh generation and adaptivity techniques is given. Basic building blocks taken from the field of computational geometry are first described. Various practical mesh generation techniques based on these algorithms are then constructed and illustrated with examples. Issues of adaptive meshing and stretched mesh generation for anisotropic problems are treated in subsequent sections. The presentation is organized in an education manner, for readers familiar with computational fluid dynamics, wishing to learn more about current unstructured mesh techniques.

Galerkin finite difference Laplacian operators on isolated unstructured triangular meshes by linear combinations

NASA Technical Reports Server (NTRS)

Baumeister, Kenneth J.

1990-01-01

The Galerkin weighted residual technique using linear triangular weight functions is employed to develop finite difference formulae in Cartesian coordinates for the Laplacian operator on isolated unstructured triangular grids. The weighted residual coefficients associated with the weak formulation of the Laplacian operator along with linear combinations of the residual equations are used to develop the algorithm. The algorithm was tested for a wide variety of unstructured meshes and found to give satisfactory results.

Binding-induced Folding of Prokaryotic Ubiquitin-like Protein on the Mycobacterium Proteasomal ATPase Targets Substrates for Degradation

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

T Wang; K Heran Darwin; H Li

2011-12-31

Mycobacterium tuberculosis uses a proteasome system that is analogous to the eukaryotic ubiquitin-proteasome pathway and is required for pathogenesis. However, the bacterial analog of ubiquitin, prokaryotic ubiquitin-like protein (Pup), is an intrinsically disordered protein that bears little sequence or structural resemblance to the highly structured ubiquitin. Thus, it was unknown how pupylated proteins were recruited to the proteasome. Here, we show that the Mycobacterium proteasomal ATPase (Mpa) has three pairs of tentacle-like coiled coils that recognize Pup. Mpa bound unstructured Pup through hydrophobic interactions and a network of hydrogen bonds, leading to the formation of an {alpha}-helix in Pup. Ourmore » work describes a binding-induced folding recognition mechanism in the Pup-proteasome system that differs mechanistically from substrate recognition in the ubiquitin-proteasome system. This key difference between the prokaryotic and eukaryotic systems could be exploited for the development of a small molecule-based treatment for tuberculosis.« less

Binding-induced folding of prokaryotic ubiquitin-like protein on the mycobacterium proteasomal ATPase targets substrates for degradation

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

Wang, T.; Li, H.; Darwin, K. H.

2010-11-01

Mycobacterium tuberculosis uses a proteasome system that is analogous to the eukaryotic ubiquitin-proteasome pathway and is required for pathogenesis. However, the bacterial analog of ubiquitin, prokaryotic ubiquitin-like protein (Pup), is an intrinsically disordered protein that bears little sequence or structural resemblance to the highly structured ubiquitin. Thus, it was unknown how pupylated proteins were recruited to the proteasome. Here, we show that the Mycobacterium proteasomal ATPase (Mpa) has three pairs of tentacle-like coiled coils that recognize Pup. Mpa bound unstructured Pup through hydrophobic interactions and a network of hydrogen bonds, leading to the formation of an {alpha}-helix in Pup. Ourmore » work describes a binding-induced folding recognition mechanism in the Pup-proteasome system that differs mechanistically from substrate recognition in the ubiquitin-proteasome system. This key difference between the prokaryotic and eukaryotic systems could be exploited for the development of a small molecule-based treatment for tuberculosis.« less

Self-Assembly of Spider Silk-Fusion Proteins Comprising Enzymatic and Fluorescence Activity.

PubMed

Humenik, Martin; Mohrand, Madeleine; Scheibel, Thomas

2018-04-18

The recombinant spider silk protein eADF4(C16) was genetically fused either with esterase 2 (EST2) or green fluorescent protein (GFP). The fusions EST-eADF4(C16) and GFP-eADF4(C16) were spectroscopically investigated and showed native structures of EST and GFP. The structural integrity was confirmed by the enzymatic activity of EST and the fluorescence of GFP. The spider silk moiety retained its intrinsically unstructured conformation in solution and the self-assembly into either nanofibrils or nanoparticles could be controlled by the concentration of phosphate. Particles, however, showed significantly lower activity of the EST and GFP domains likely caused by a steric hindrance. However, upon self-assembly of EST-eADF4(C16) and GFP-eADF4(C16) into fibrils the protein activities were retained. In general, the fusion of globular enzymes with the spider silk domain allows the generation of fibrous biomaterials with catalytic or light emitting properties.

The LC Domain of hnRNPA2 Adopts Similar Conformations in Hydrogel Polymers, Liquid-like Droplets and Nuclei

PubMed Central

Xiang, Siheng; Kato, Masato; Wu, Leeju; Lin, Yi; Ding, Ming; Zhang, Yajie; Yu, Yonghao; McKnight, Steven L.

2016-01-01

SUMMARY Many DNA and RNA regulatory proteins contain polypeptide domains that are unstructured when analyzed in cell lysates. These domains are typified by an over-representation of a limited number of amino acids and have been termed prion-like, intrinsically disordered or low complexity (LC) domains. When incubated at high concentration, certain of these LC domains polymerize into labile, amyloid-like fibers. Here we report methods allowing the generation of a molecular footprint of the polymeric state of the LC domain of hnRNPA2. By deploying this footprinting technique to probe the structure of the native hnRNPA2 protein present in isolated nuclei, we offer evidence that its LC domain exists in a similar conformation as that described for recombinant polymers of the protein. These observations favor biologic utility to the polymerization of LC domains in the pathway of information transfer from gene to message to protein. PMID:26544936

An updated version of NPIDB includes new classifications of DNA–protein complexes and their families

PubMed Central

Zanegina, Olga; Kirsanov, Dmitriy; Baulin, Eugene; Karyagina, Anna; Alexeevski, Andrei; Spirin, Sergey

2016-01-01

The recent upgrade of nucleic acid–protein interaction database (NPIDB, http://npidb.belozersky.msu.ru/) includes a newly elaborated classification of complexes of protein domains with double-stranded DNA and a classification of families of related complexes. Our classifications are based on contacting structural elements of both DNA: the major groove, the minor groove and the backbone; and protein: helices, beta-strands and unstructured segments. We took into account both hydrogen bonds and hydrophobic interaction. The analyzed material contains 1942 structures of protein domains from 748 PDB entries. We have identified 97 interaction modes of individual protein domain–DNA complexes and 17 DNA–protein interaction classes of protein domain families. We analyzed the sources of diversity of DNA–protein interaction modes in different complexes of one protein domain family. The observed interaction mode is sometimes influenced by artifacts of crystallization or diversity in secondary structure assignment. The interaction classes of domain families are more stable and thus possess more biological sense than a classification of single complexes. Integration of the classification into NPIDB allows the user to browse the database according to the interacting structural elements of DNA and protein molecules. For each family, we present average DNA shape parameters in contact zones with domains of the family. PMID:26656949

The Contribution of the Division of Radiophysics Murraybank Field Station to International Radio Astronomy

NASA Astrophysics Data System (ADS)

Wendt, Harry; Orchiston, Wayne; Slee, Bruce

During the 1950s Australia was one of the world's foremost astronomical nations owing primarily to the work of the dynamic radio astronomy group within the Commonwealth Scientific and Industrial Research Organisation's Division of Radiophysics. Most of the observations were made at the network of field stations maintained by the Division in or near Sydney, and one of these field stations was Murraybank in the north-western suburbs of Sydney. GVaucouleursDe1954The Magellanic Clouds and the GalaxyThe Observatory7423311954Obs....74...23DDe Vaucouleurs, G., 1954a. The Magellanic Clouds and the Galaxy. The Observatory, 74, 23-31. GVaucouleursDe1954The Magellanic Clouds and the Galaxy, IIThe Observatory741581641954Obs....74..158DDe Vaucouleurs, G., 1954b. The Magellanic Clouds and the Galaxy, II. The Observatory, 74, 158-164. GVaucouleursDe1961Classification and radial velocities of bright southern galaxiesMemoirs of the Royal Astronomical Society6869871961MmRAS..68...69DDe Vaucouleurs, G., 1961. Classification and radial velocities of bright southern galaxies. Memoirs of the Royal Astronomical Society, 68, 69-87. JDeane2006Vacuum Tube SupercomputerSydneyScience Foundation for Physics and the Australian Computer Museum SocietyDeane, J., 2006. Vacuum Tube Supercomputer. Sydney, Science Foundation for Physics and the Australian Computer Museum Society. NHDeiter1965Neutral hydrogen near the galactic polesAstErickson, W.C., Helfer, H.L., and Tatel, H.E., 1959. A survey of neutral hydrogen at high galactic latitudes. In Bracewell, 390-397. MWFeastADThackerayAJWesselink1957Radial velocities of southern B stars determined at the Radcliffe Observatory (Paper II) (summary)Monthly Notices of the Royal Astronomical Society1175791957MNRAS.117..579FFeast, M.W., Thackeray, A.D., and Wesselink, A.J., 1957. 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DSMathewsonSRWayteVLFordKRuan1987The `high velocity cloud' origin of the Magellanic systemProceedings of the Astronomical Society of Australia719251987PASAu...7...19MMathewson, D.S., Wayte, S.R., Ford, V.L., and Ruan, K., 1987. The `high velocity cloud' origin of the Magellanic system. Proceedings of the Astronomical Society of Australia, 7, 19-25. NMMcClure-GriffithsLStaveley-SmithFJLockmanMRCalabrettaHAFordPMWKalberlaTMurphyHNakanishiDJPisano2008An interaction of a Magellanic leading arm high-velocity cloud with the Milky Way diskAstrophysical Journal673L143L1462008ApJ...673L.143M10.1086/528683McClure-Griffiths, N.M., Staveley-Smith, L., Lockman, F.J., Calabretta, M.R., Ford, H.A., Kalberla, P.M. W., Murphy, T., Nakanishi, H., and Pisano, D.J., 2008. An interaction of a Magellanic leading arm high-velocity cloud with the Milky Way disk. Astrophysical Journal, 673, L143-L146. McCready, L.L., 1954. Letter to J.L. Pawsey, dated 19 August. 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The general distribution and motions of the local gas. Australian Journal of Physics, 14, 260-278. McGee, R.X., Murray, J.D., and Milton, J.A., 1963. A sky survey of neutral hydrogen at λ 21 cm. II. The detailed distribution of low velocity gas. Australian Journal of Physics, 16, 136-170. RXMcGeeJDMurrayJLPawsey1961Streaming of interstellar hydrogen in the vicinity of the SunNature1899579591961Natur.189..957M10.1038/189957a0McGee, R.X., Murray, J.D., and Pawsey, J.L., 1961. Streaming of interstellar hydrogen in the vicinity of the Sun. Nature, 189, 957-959. KMMentenMJReidJForbrichABrunthaler2007The distance to the Orion NebulaAstronomy and Astrophysics4745155202007A&A...474..515M10.1051/0004-6361:20078247Menten, K.M., Reid, M.J., Forbrich, J., and Brunthaler, A., 2007. The distance to the Orion Nebula. Astronomy and Astrophysics, 474, 515-520. CAMullerGWesterhout1957A catalogue of 21-cm line profilesBulletin of the Astronomical Institutes of the Netherlands131511951957BAN....13..151MMuller, C.A., and Westerhout, G., 1957. A catalogue of 21-cm line profiles. Bulletin of the Astronomical Institutes of the Netherlands, 13, 151-195. JDMurrayRXMcGee1958A new hydrogen cloud in Pyxis-HydraThe Observatory782422441958Obs....78..242MMurray, J.D., and McGee, R.X., 1958. A new hydrogen cloud in Pyxis-Hydra. The Observatory, 78, 242-244. JDMurrayRXMcGee1959Neutral hydrogen gas in the Taurus-Orion region observed with a multichannel 21 cm line receiverAustralian Journal of Physics121271331959AuJPh..12..127M10.1071/PH590127Murray, J.D., and McGee, R.X., 1959. Neutral hydrogen gas in the Taurus-Orion region observed with a multichannel 21 cm line receiver. Australian Journal of Physics, 12, 127-133. JDMurrayRXMcGee1963A multi-channel hydrogen line (21 cm) receiverProceedings of the Institute of Radio Engineers Australia24191196Murray, J.D., and McGee, R.X., 1963. A multi-channel hydrogen line (21 cm) receiver. Proceedings of the Institute of Radio Engineers Australia, 24, 191-196. AOllongrenHCHulstvan de1957Corrections of 21-cm line profilesBulletin of the Astronomical Institutes of the Netherlands131962001957BAN....13..196OOllongren, A., and van de Hulst, H.C., 1957. Corrections of 21-cm line profiles. Bulletin of the Astronomical Institutes of the Netherlands, 13, 196-200. WOrchiston1993New Zealand's role in the identification of the first "radio stars"Southern Stars3546521993SouSt..35...46OOrchiston, W., 1993. New Zealand's role in the identification of the first "radio stars." Southern Stars, 35, 46-52. WOrchiston1994John Bolton, discrete sources, and the New Zealand field-trip of 1948Australian Journal of Physics475415471994AuJPh..47..541OOrchiston, W., 1994. John Bolton, discrete sources, and the New Zealand field-trip of 1948. Australian Journal of Physics, 47, 541-547 Orchiston, W., 2004. The rise and fall of the Chris Cross: a pioneering Australian radio telescope. In Orchiston, W., Stephenson, R., Debarbat, S., and Nha, I.-S. (eds.). Astronomical Instruments and Archives from the Asia-Pacific Region. Seoul, IAU Commission 41. Pp. 157-162. WOrchistonDMathewson2009Chris Christiansen and the Chris CrossJournal of Astronomical History and Heritage1211322009JAHH...12...11OOrchiston, W., and Mathewson, D., 2009. Chris Christiansen and the Chris Cross. Journal of Astronomical History and Heritage, 12, 11-32. WOrchistonBSlee2002Ingenuity and initiative in Australian radio astronomy: the Dover Heights `hole-in-the-ground' antennaJournal of Astronomical History and Heritage521342002JAHH....5...21OOrchiston, W., and Slee, B., 2002. Ingenuity and initiative in Australian radio astronomy: the Dover Heights `hole-in-the-ground' antenna. Journal of Astronomical History and Heritage, 5, 21-34. WOrchistonBSlee2005The Radiophysics field stations and the early development of radio astronomyWOrchistonThe New Astronomy: Opening the Electromagnetic Window and Expanding our View of Planet EarthSpringer. PpDordrecht11916810.1007/1-4020-3724-4_8Orchiston, W., and Slee, B., 2005. The Radiophysics field stations and the early development of radio astronomy. In Orchiston, W. (ed.). The New Astronomy: Opening the Electromagnetic Window and Expanding our View of Planet Earth. Dordrecht, Springer. Pp. 119-168. WOrchistonTNakamuraRStrom2011Highlighting the History of Astronomy in the Asia-Pacific RegionNew YorkSpringerOrchiston, W., Nakamura, T., and Strom, R. (eds.), 2011. Highlighting the History of Astronomy in the Asia-Pacific Region. New York, Springer. AEERodgersKADudevoirJCCarterBJFanousEKratzenberg2005Deuterium abundance in the interstellar gas of the Galactic Anticentre from the 327 MHz LineAstrophysical Journal630L41L442005ApJ...630L..41R10.1086/466524Rodgers, A.E.E., Dudevoir, K.A., Carter, J.C., Fanous, B.J., and Kratzenberg, E., 2005. Deuterium abundance in the interstellar gas of the Galactic Anticentre from the 327 MHz Line. Astrophysical Journal, 630, L41-L44. VCRubinWKFord1970Rotation of the Andromeda Nebula from a spectroscopic survey of emission regionsAstrophysical Journal1593794031970ApJ...159..379R10.1086/150317Rubin, V.C., and Ford, W.K., 1970. Rotation of the Andromeda Nebula from a spectroscopic survey of emission regions. Astrophysical Journal, 159, 379-403. MSchmidt1957Spiral structure in the inner parts of the galactic system derived from the hydrogen emission at 21-cm wavelengthBulletin of the Astronomical Institutes of the Netherlands132472681957BAN....13..247SSchmidt, M., 1957. Spiral structure in the inner parts of the galactic system derived from the hydrogen emission at 21-cm wavelength. Bulletin of the Astronomical Institutes of the Netherlands, 13, 247-268. GAShain1957The inclination to the Galactic Equator of the general magnetic field of LSSparkeJSGallagher2000Galaxies in the Universe: An IntroductionCambridge University PressCambridgeSparke, L.S., and Gallagher, J.S., 2000. Galaxies in the Universe: An Introduction, Cambridge, Cambridge University Press. SStanimirovicLStaveley-SmithJMDickeyRJSaultSLSnowden1999The large-scale HI structure of the Small Magellanic CloudMonthly Notices of the Royal Astronomical Society3024174361999MNRAS.302..417S10.1046/j.1365-8711.1999.02013.xStanimirovic, S., Staveley-Smith, L., Dickey, J.M., Sault, R.J., and Snowden, S.L., 1999. The large-scale HI structure of the Small Magellanic Cloud. Monthly Notices of the Royal Astronomical Society, 302, 417-436. 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Unstructured mesh algorithms for aerodynamic calculations

NASA Technical Reports Server (NTRS)

Mavriplis, D. J.

1992-01-01

The use of unstructured mesh techniques for solving complex aerodynamic flows is discussed. The principle advantages of unstructured mesh strategies, as they relate to complex geometries, adaptive meshing capabilities, and parallel processing are emphasized. The various aspects required for the efficient and accurate solution of aerodynamic flows are addressed. These include mesh generation, mesh adaptivity, solution algorithms, convergence acceleration, and turbulence modeling. Computations of viscous turbulent two-dimensional flows and inviscid three-dimensional flows about complex configurations are demonstrated. Remaining obstacles and directions for future research are also outlined.

Multigrid solution of internal flows using unstructured solution adaptive meshes

NASA Technical Reports Server (NTRS)

Smith, Wayne A.; Blake, Kenneth R.

1992-01-01

This is the final report of the NASA Lewis SBIR Phase 2 Contract Number NAS3-25785, Multigrid Solution of Internal Flows Using Unstructured Solution Adaptive Meshes. The objective of this project, as described in the Statement of Work, is to develop and deliver to NASA a general three-dimensional Navier-Stokes code using unstructured solution-adaptive meshes for accuracy and multigrid techniques for convergence acceleration. The code will primarily be applied, but not necessarily limited, to high speed internal flows in turbomachinery.

Quantum Cosmology

NASA Astrophysics Data System (ADS)

Bojowald, Martin

The universe, ultimately, is to be described by quantum theory. Quantum aspects of all there is, including space and time, may not be significant for many purposes, but are crucial for some. And so a quantum description of cosmology is required for a complete and consistent worldview. At any rate, even if we were not directly interested in regimes where quantum cosmology plays a role, a complete physical description could not stop at a stage before the whole universe is reached. Quantum theory is essential in the microphysics of particles, atoms, molecules, solids, white dwarfs and neutron stars. Why should one expect this ladder of scales to end at a certain size? 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Characterizing Flexible and Instrinsically Unstructured Biological Macromolecules by SAS using the Porod-Debye Law

PubMed Central

Rambo, Robert P.; Tainer, John A.

2011-01-01

Unstructured proteins, RNA or DNA components provide functionally important flexibility that is key to many macromolecular assemblies throughout cell biology. As objective, quantitative experimental measures of flexibility and disorder in solution are limited, small angle scattering (SAS), and in particular small angle X-ray scattering (SAXS), provides a critical technology to assess macromolecular flexibility as well as shape and assembly. Here, we consider the Porod-Debye law as a powerful tool for detecting biopolymer flexibility in SAS experiments. We show that the Porod-Debye region fundamentally describes the nature of the scattering intensity decay, which captures information needed for distinguishing between folded and flexible particles. Particularly for comparative SAS experiments, application of the law, as described here, can distinguish between discrete conformational changes and localized flexibility relevant to molecular recognition and interaction networks. This approach aids insightful analyses of fully and partly flexible macromolecules that is more robust and conclusive than traditional Kratky analyses. Furthermore, we demonstrate for prototypic SAXS data that the ability to calculate particle density by the Porod-Debye criteria, as shown here, provides an objective quality assurance parameter that may prove of general use for SAXS modeling and validation. PMID:21509745

Mechanical Properties of β-Catenin Revealed by Single-Molecule Experiments

PubMed Central

Valbuena, Alejandro; Vera, Andrés Manuel; Oroz, Javier; Menéndez, Margarita; Carrión-Vázquez, Mariano

2012-01-01

β-catenin is a central component of the adaptor complex that links cadherins to the actin cytoskeleton in adherens junctions and thus, it is a good candidate to sense and transmit mechanical forces to trigger specific changes inside the cell. To fully understand its molecular physiology, we must first investigate its mechanical role in mechanotransduction within the cadherin system. We have studied the mechanical response of β-catenin to stretching using single-molecule force spectroscopy and molecular dynamics. Unlike most proteins analyzed to date, which have a fixed mechanical unfolding pathway, the β-catenin armadillo repeat region (ARM) displays low mechanostability and multiple alternative unfolding pathways that seem to be modulated by its unstructured termini. These results are supported by steered molecular dynamics simulations, which also predict its mechanical stabilization and unfolding pathway restrictions when the contiguous α-helix of the C-terminal unstructured region is included. Furthermore, simulations of the ARM/E-cadherin cytosolic tail complex emulating the most probable stress geometry occurring in vivo show a mechanical stabilization of the interaction whose magnitude correlates with the length of the stretch of the cadherin cytosolic tail that is in contact with the ARM region. PMID:23083718

Dynamics of partially folded and unfolded proteins investigated with quasielastic neutron spectroscopy

NASA Astrophysics Data System (ADS)

Stadler, Andreas M.

2018-05-01

Molecular dynamics in proteins animate and play a vital role for biologically relevant processes of these biomacromolecules. Quasielastic incoherent neutron scattering (QENS) is a well-suited experimental method to study protein dynamics from the picosecond to several nanoseconds and in the Ångström length-scale. In QENS experiments of protein solutions hydrogens act as reporters for the motions of methyl groups or amino acids to which they are bound. Neutron Spin-Echo spectroscopy (NSE) offers the highest energy resolution in the field of neutron spectroscopy and allows the study of slow collective motions in proteins up to several hundred nanoseconds and in the nanometer length-scale. In the following manuscript I will review recent studies that stress the relevance of molecular dynamics for protein folding and for conformational transitions of intrinsically disordered proteins (IDPs). During the folding collapse the protein is exploring its accessible conformational space via molecular motions. A large flexibility of partially folded and unfolded proteins, therefore, is mandatory for rapid protein folding. IDPs are a special case as they are largely unstructured under physiological conditions. A large flexibility is a characteristic property of IDPs as it allows, for example, the interaction with various binding partners or the rapid response to different conditions.

A Bipartite Interaction between Hsp70 and CHIP Regulates Ubiquitination of Chaperoned Client Proteins

DOE PAGES

Zhang, Huaqun; Amick, Joseph; Chakravarti, Ritu; ...

2015-02-12

The ubiquitin ligase CHIP plays an important role in cytosolic protein quality control by ubiquitinating proteins chaperoned by Hsp70/Hsc70 and Hsp90, thereby targeting such substrate proteins for degradation. We present a 2.91 Å resolution structure of the tetratricopeptide repeat (TPR) domain of CHIP in complex with the α-helical lid subdomain and unstructured tail of Hsc70. Surprisingly, the CHIP-TPR interacts with determinants within both the Hsc70-lid subdomain and the C-terminal PTIEEVD motif of the tail, exhibiting an atypical mode of interaction between chaperones and TPR domains. Here, we demonstrate that the interaction between CHIP and the Hsc70-lid subdomain is required formore » proper ubiquitination of Hsp70/Hsc70 or Hsp70/Hsc70-bound substrate proteins. Posttranslational modifications of the Hsc70 lid and tail disrupt key contacts with the CHIP-TPR and may regulate CHIP-mediated ubiquitination. Our study shows how CHIP docks onto Hsp70/Hsc70 and defines a bipartite mode of interaction between TPR domains and their binding partners.« less

Quantum search of a real unstructured database

NASA Astrophysics Data System (ADS)

Broda, Bogusław

2016-02-01

A simple circuit implementation of the oracle for Grover's quantum search of a real unstructured classical database is proposed. The oracle contains a kind of quantumly accessible classical memory, which stores the database.

Parallel deterministic transport sweeps of structured and unstructured meshes with overloaded mesh decompositions

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

Pautz, Shawn D.; Bailey, Teresa S.

Here, the efficiency of discrete ordinates transport sweeps depends on the scheduling algorithm, the domain decomposition, the problem to be solved, and the computational platform. Sweep scheduling algorithms may be categorized by their approach to several issues. In this paper we examine the strategy of domain overloading for mesh partitioning as one of the components of such algorithms. In particular, we extend the domain overloading strategy, previously defined and analyzed for structured meshes, to the general case of unstructured meshes. We also present computational results for both the structured and unstructured domain overloading cases. We find that an appropriate amountmore » of domain overloading can greatly improve the efficiency of parallel sweeps for both structured and unstructured partitionings of the test problems examined on up to 10 5 processor cores.« less

Parallel deterministic transport sweeps of structured and unstructured meshes with overloaded mesh decompositions

DOE PAGES

Pautz, Shawn D.; Bailey, Teresa S.

2016-11-29

Here, the efficiency of discrete ordinates transport sweeps depends on the scheduling algorithm, the domain decomposition, the problem to be solved, and the computational platform. Sweep scheduling algorithms may be categorized by their approach to several issues. In this paper we examine the strategy of domain overloading for mesh partitioning as one of the components of such algorithms. In particular, we extend the domain overloading strategy, previously defined and analyzed for structured meshes, to the general case of unstructured meshes. We also present computational results for both the structured and unstructured domain overloading cases. We find that an appropriate amountmore » of domain overloading can greatly improve the efficiency of parallel sweeps for both structured and unstructured partitionings of the test problems examined on up to 10 5 processor cores.« less

Neural correlates of processing sentences and compound words in Chinese

PubMed Central

Hung, Yi-Hui; Tzeng, Ovid; Wu, Denise H.

2017-01-01

Sentence reading involves multiple linguistic operations including processing of lexical and compositional semantics, and determining structural and grammatical relationships among words. Previous studies on Indo-European languages have associated left anterior temporal lobe (aTL) and left interior frontal gyrus (IFG) with reading sentences compared to reading unstructured word lists. To examine whether these brain regions are also involved in reading a typologically distinct language with limited morphosyntax and lack of agreement between sentential arguments, an FMRI study was conducted to compare passive reading of Chinese sentences, unstructured word lists and disconnected character lists that are created by only changing the order of an identical set of characters. Similar to previous findings from other languages, stronger activation was found in mainly left-lateralized anterior temporal regions (including aTL) for reading sentences compared to unstructured word and character lists. On the other hand, stronger activation was identified in left posterior temporal sulcus for reading unstructured words compared to unstructured characters. Furthermore, reading unstructured word lists compared to sentences evoked stronger activation in left IFG and left inferior parietal lobule. Consistent with the literature on Indo-European languages, the present results suggest that left anterior temporal regions subserve sentence-level integration, while left IFG supports restoration of sentence structure. In addition, left posterior temporal sulcus is associated with morphological compounding. Taken together, reading Chinese sentences engages a common network as reading other languages, with particular reliance on integration of semantic constituents. PMID:29194453

A nonlinear model predictive control formulation for obstacle avoidance in high-speed autonomous ground vehicles in unstructured environments

NASA Astrophysics Data System (ADS)

Liu, Jiechao; Jayakumar, Paramsothy; Stein, Jeffrey L.; Ersal, Tulga

2018-06-01

This paper presents a nonlinear model predictive control (MPC) formulation for obstacle avoidance in high-speed, large-size autono-mous ground vehicles (AGVs) with high centre of gravity (CoG) that operate in unstructured environments, such as military vehicles. The term 'unstructured' in this context denotes that there are no lanes or traffic rules to follow. Existing MPC formulations for passenger vehicles in structured environments do not readily apply to this context. Thus, a new nonlinear MPC formulation is developed to navigate an AGV from its initial position to a target position at high-speed safely. First, a new cost function formulation is used that aims to find the shortest path to the target position, since no reference trajectory exists in unstructured environments. Second, a region partitioning approach is used in conjunction with a multi-phase optimal control formulation to accommodate the complicated forms the obstacle-free region can assume due to the presence of multiple obstacles in the prediction horizon in an unstructured environment. Third, the no-wheel-lift-off condition, which is the major dynamical safety concern for high-speed, high-CoG AGVs, is ensured by limiting the steering angle within a range obtained offline using a 14 degrees-of-freedom vehicle dynamics model. Thus, a safe, high-speed navigation is enabled in an unstructured environment. Simulations of an AGV approaching multiple obstacles are provided to demonstrate the effectiveness of the algorithm.

Advanced ensemble modelling of flexible macromolecules using X-ray solution scattering.

PubMed

Tria, Giancarlo; Mertens, Haydyn D T; Kachala, Michael; Svergun, Dmitri I

2015-03-01

Dynamic ensembles of macromolecules mediate essential processes in biology. Understanding the mechanisms driving the function and molecular interactions of 'unstructured' and flexible molecules requires alternative approaches to those traditionally employed in structural biology. Small-angle X-ray scattering (SAXS) is an established method for structural characterization of biological macromolecules in solution, and is directly applicable to the study of flexible systems such as intrinsically disordered proteins and multi-domain proteins with unstructured regions. The Ensemble Optimization Method (EOM) [Bernadó et al. (2007 ▶). J. Am. Chem. Soc. 129, 5656-5664] was the first approach introducing the concept of ensemble fitting of the SAXS data from flexible systems. In this approach, a large pool of macromolecules covering the available conformational space is generated and a sub-ensemble of conformers coexisting in solution is selected guided by the fit to the experimental SAXS data. This paper presents a series of new developments and advancements to the method, including significantly enhanced functionality and also quantitative metrics for the characterization of the results. Building on the original concept of ensemble optimization, the algorithms for pool generation have been redesigned to allow for the construction of partially or completely symmetric oligomeric models, and the selection procedure was improved to refine the size of the ensemble. Quantitative measures of the flexibility of the system studied, based on the characteristic integral parameters of the selected ensemble, are introduced. These improvements are implemented in the new EOM version 2.0, and the capabilities as well as inherent limitations of the ensemble approach in SAXS, and of EOM 2.0 in particular, are discussed.

Multi-scale and multi-physics model of the uterine smooth muscle with mechanotransduction.

PubMed

Yochum, Maxime; Laforêt, Jérémy; Marque, Catherine

2018-02-01

Preterm labor is an important public health problem. However, the efficiency of the uterine muscle during labor is complex and still poorly understood. This work is a first step towards a model of the uterine muscle, including its electrical and mechanical components, to reach a better understanding of the uterus synchronization. This model is proposed to investigate, by simulation, the possible role of mechanotransduction for the global synchronization of the uterus. The electrical diffusion indeed explains the local propagation of contractile activity, while the tissue stretching may play a role in the synchronization of distant parts of the uterine muscle. This work proposes a multi-physics (electrical, mechanical) and multi-scales (cell, tissue, whole uterus) model, which is applied to a realistic uterus 3D mesh. This model includes electrical components at different scales: generation of action potentials at the cell level, electrical diffusion at the tissue level. It then links these electrical events to the mechanical behavior, at the cellular level (via the intracellular calcium concentration), by simulating the force generated by each active cell. It thus computes an estimation of the intra uterine pressure (IUP) by integrating the forces generated by each active cell at the whole uterine level, as well as the stretching of the tissue (by using a viscoelastic law for the behavior of the tissue). It finally includes at the cellular level stretch activated channels (SACs) that permit to create a loop between the mechanical and the electrical behavior (mechanotransduction). The simulation of different activated regions of the uterus, which in this first "proof of concept" case are electrically isolated, permits the activation of inactive regions through the stretching (induced by the electrically active regions) computed at the whole organ scale. This permits us to evidence the role of the mechanotransduction in the global synchronization of the uterus. The results also permit us to evidence the effect on IUP of this enhanced synchronization induced by the presence of SACs. This proposed simplified model will be further improved in order to permit a better understanding of the global uterine synchronization occurring during efficient labor contractions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Risk factors and clinical features of ovarian pregnancy: a case–control study

PubMed Central

Zhu, Qian; Li, Cheng; Zhao, Wei-Hong; Yuan, Jiang-Jing; Yan, Ming-Xing; Qin, Guo-Juan; Zhang, Jian

2014-01-01

Objective To identify risk factors for ovarian pregnancy (OP) and compare clinical features between OP and tubal pregnancy (TP) patients. Design Case–control study. Setting University hospital. Participants A case–control study was conducted from January 2005 to May 2014. Women diagnosed with OP were recruited as the case group (n=71), 145 women with TP and 146 with intrauterine pregnancy (IUP) were matched as controls at a ratio of 1:2:2. Women who refused interviews or provided incomplete information were excluded. Results OP risk was lower than TP risk in women with serological evidence of Chlamydia trachomatis infection (adjusted OR1 0.17, 95% CI 0.06 to 0.52), previous adnexal surgery (adjusted OR1 0.25, 95% CI 0.07 to 0.95), and current levonorgestrel emergency contraceptive use (adjusted OR1 0.24, 95% CI 0.07 to 0.78). In vitro fertilisation-embryo transfer (IVF-ET) carried a higher risk of OP (adjusted OR1 12.18, 95% CI 2.23 to 66.58) than natural conception. When Controlled by IUP women, current users of intrauterine devices (IUDs) carried a higher risk of OP than non-users of any contraceptives (adjusted OR2 9.60, 95% CI 1.76 to 42.20). β-Human chorionic gonadotropin (hCG) levels on the day of surgery were higher in OP patients than in TP patients (p<0.01). Women with OP were less likely to initially present with vaginal bleeding than those with TP (p=0.02). Moreover, shock (p=0.02), rupture (p<0.01), haemoperitoneum (p<0.01) and emergency laparotomy (p<0.01) were more common in the OP group than in the TP group. Conclusions IVF-ET and IUD use may be risk factors for OP, and OP patients tend to have high β-hCG levels and a poor clinical outcome (shock, rupture, haemoperitoneum and need for emergency laparotomy). Our findings may contribute to the prevention and early diagnosis of OP. PMID:25472658

Warehousing Structured and Unstructured Data for Data Mining.

ERIC Educational Resources Information Center

Miller, L. L.; Honavar, Vasant; Barta, Tom

1997-01-01

Describes an extensible object-oriented view system that supports the integration of both structured and unstructured data sources in either the multidatabase or data warehouse environment. Discusses related work and data mining issues. (AEF)

Identification of HYPK-Interacting Proteins Reveals Involvement of HYPK in Regulating Cell Growth, Cell Cycle, Unfolded Protein Response and Cell Death

PubMed Central

Choudhury, Kamalika Roy; Raychaudhuri, Swasti; Bhattacharyya, Nitai P.

2012-01-01

Huntingtin Yeast Two-Hybrid Protein K (HYPK) is an intrinsically unstructured huntingtin (HTT)-interacting protein with chaperone-like activity. To obtain more information about the function(s) of the protein, we identified 27 novel interacting partners of HYPK by pull-down assay coupled with mass spectrometry and, further, 9 proteins were identified by co-localization and co-immunoprecipitation (co-IP) assays. In neuronal cells, (EEF1A1 and HSPA1A), (HTT and LMNB2) and (TP53 and RELA) were identified in complex with HYPK in different experiments. Various Gene Ontology (GO) terms for biological processes, like protein folding (GO: 0006457), response to unfolded protein (GO: 0006986), cell cycle arrest (GO: 0007050), anti-apoptosis (GO: 0006916) and regulation of transcription (GO: 0006355) were significantly enriched with the HYPK-interacting proteins. Cell growth and the ability to refold heat-denatured reporter luciferase were decreased, but cytotoxicity was increased in neuronal cells where HYPK was knocked-down using HYPK antisense DNA construct. The proportion of cells in different phases of cell cycle was also altered in cells with reduced levels of HYPK. These results show that HYPK is involved in several biological processes, possibly through interaction with its partners. PMID:23272104

Unfolding and refolding details of lysozyme in the presence of β-casein micelles.

PubMed

Wu, Fu-Gen; Luo, Jun-Jie; Yu, Zhi-Wu

2011-02-28

In this work, we selected a small globular protein, lysozyme, to study how it unfolds and refolds in the presence of micelles composed of the unstructured β-casein proteins by using microcalorimetry and circular dichroism spectroscopy. It was found that a partially unfolded structure of lysozyme starts to form when the β-casein/lysozyme molar ratio is above 0.7, and the structure forms exclusively when the β-casein/lysozyme molar ratio is above 1.6. This partially unfolded state of lysozyme loses most of its tertiary structure and after heating, the denatured lysozyme molecules are trapped in the charged coatings of β-casein micelles and cannot refold upon cooling. The thus obtained protein complex can be viewed as a kind of special polyelectrolyte complex micelle. The net charge ratios of the two proteins and the ionic strength of the dispersions can significantly modulate the electrostatic and hydrophobic interactions between the two proteins. Our present work may have implications for the nanoparticle protein engineering therapy in the biomedicine field and may provide a better understanding of the principles governing the protein-protein interactions. Besides, the heating-cooling-reheating procedure employed in this work can also be used to study the unfolding and refolding details of the target protein in other protein-protein, protein-polymer and protein-small solute systems.

Tuned grid generation with ICEM CFD

NASA Technical Reports Server (NTRS)

Wulf, Armin; Akdag, Vedat

1995-01-01

ICEM CFD is a CAD based grid generation package that supports multiblock structured, unstructured tetrahedral and unstructured hexahedral grids. Major development efforts have been spent to extend ICEM CFD's multiblock structured and hexahedral unstructured grid generation capabilities. The modules added are: a parametric grid generation module and a semi-automatic hexahedral grid generation module. A fully automatic version of the hexahedral grid generation module for around a set of predefined objects in rectilinear enclosures has been developed. These modules will be presented and the procedures used will be described, and examples will be discussed.

A three-dimensional structured/unstructured hybrid Navier-Stokes method for turbine blade rows

NASA Technical Reports Server (NTRS)

Tsung, F.-L.; Loellbach, J.; Kwon, O.; Hah, C.

1994-01-01

A three-dimensional viscous structured/unstructured hybrid scheme has been developed for numerical computation of high Reynolds number turbomachinery flows. The procedure allows an efficient structured solver to be employed in the densely clustered, high aspect-ratio grid around the viscous regions near solid surfaces, while employing an unstructured solver elsewhere in the flow domain to add flexibility in mesh generation. Test results for an inviscid flow over an external transonic wing and a Navier-Stokes flow for an internal annular cascade are presented.

Application of an unstructured grid flow solver to planes, trains and automobiles

NASA Technical Reports Server (NTRS)

Spragle, Gregory S.; Smith, Wayne A.; Yadlin, Yoram

1993-01-01

Rampant, an unstructured flow solver developed at Fluent Inc., is used to compute three-dimensional, viscous, turbulent, compressible flow fields within complex solution domains. Rampant is an explicit, finite-volume flow solver capable of computing flow fields using either triangular (2d) or tetrahedral (3d) unstructured grids. Local time stepping, implicit residual smoothing, and multigrid techniques are used to accelerate the convergence of the explicit scheme. The paper describes the Rampant flow solver and presents flow field solutions about a plane, train, and automobile.

Unstructured grids on SIMD torus machines

NASA Technical Reports Server (NTRS)

Bjorstad, Petter E.; Schreiber, Robert

1994-01-01

Unstructured grids lead to unstructured communication on distributed memory parallel computers, a problem that has been considered difficult. Here, we consider adaptive, offline communication routing for a SIMD processor grid. Our approach is empirical. We use large data sets drawn from supercomputing applications instead of an analytic model of communication load. The chief contribution of this paper is an experimental demonstration of the effectiveness of certain routing heuristics. Our routing algorithm is adaptive, nonminimal, and is generally designed to exploit locality. We have a parallel implementation of the router, and we report on its performance.

An Efficient Algorithm for Mapping Imaging Data to 3D Unstructured Grids in Computational Biomechanics

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

Einstein, Daniel R.; Kuprat, Andrew P.; Jiao, Xiangmin

2013-01-01

Geometries for organ scale and multiscale simulations of organ function are now routinely derived from imaging data. However, medical images may also contain spatially heterogeneous information other than geometry that are relevant to such simulations either as initial conditions or in the form of model parameters. In this manuscript, we present an algorithm for the efficient and robust mapping of such data to imaging based unstructured polyhedral grids in parallel. We then illustrate the application of our mapping algorithm to three different mapping problems: 1) the mapping of MRI diffusion tensor data to an unstuctured ventricular grid; 2) the mappingmore » of serial cyro-section histology data to an unstructured mouse brain grid; and 3) the mapping of CT-derived volumetric strain data to an unstructured multiscale lung grid. Execution times and parallel performance are reported for each case.« less

Large-scale Parallel Unstructured Mesh Computations for 3D High-lift Analysis

NASA Technical Reports Server (NTRS)

Mavriplis, Dimitri J.; Pirzadeh, S.

1999-01-01

A complete "geometry to drag-polar" analysis capability for the three-dimensional high-lift configurations is described. The approach is based on the use of unstructured meshes in order to enable rapid turnaround for complicated geometries that arise in high-lift configurations. Special attention is devoted to creating a capability for enabling analyses on highly resolved grids. Unstructured meshes of several million vertices are initially generated on a work-station, and subsequently refined on a supercomputer. The flow is solved on these refined meshes on large parallel computers using an unstructured agglomeration multigrid algorithm. Good prediction of lift and drag throughout the range of incidences is demonstrated on a transport take-off configuration using up to 24.7 million grid points. The feasibility of using this approach in a production environment on existing parallel machines is demonstrated, as well as the scalability of the solver on machines using up to 1450 processors.

On Adding Structure to Unstructured Overlay Networks

NASA Astrophysics Data System (ADS)

Leitão, João; Carvalho, Nuno A.; Pereira, José; Oliveira, Rui; Rodrigues, Luís

Unstructured peer-to-peer overlay networks are very resilient to churn and topology changes, while requiring little maintenance cost. Therefore, they are an infrastructure to build highly scalable large-scale services in dynamic networks. Typically, the overlay topology is defined by a peer sampling service that aims at maintaining, in each process, a random partial view of peers in the system. The resulting random unstructured topology is suboptimal when a specific performance metric is considered. On the other hand, structured approaches (for instance, a spanning tree) may optimize a given target performance metric but are highly fragile. In fact, the cost for maintaining structures with strong constraints may easily become prohibitive in highly dynamic networks. This chapter discusses different techniques that aim at combining the advantages of unstructured and structured networks. Namely we focus on two distinct approaches, one based on optimizing the overlay and another based on optimizing the gossip mechanism itself.

An unstructured grid, three-dimensional model based on the shallow water equations

USGS Publications Warehouse

Casulli, V.; Walters, R.A.

2000-01-01

A semi-implicit finite difference model based on the three-dimensional shallow water equations is modified to use unstructured grids. There are obvious advantages in using unstructured grids in problems with a complicated geometry. In this development, the concept of unstructured orthogonal grids is introduced and applied to this model. The governing differential equations are discretized by means of a semi-implicit algorithm that is robust, stable and very efficient. The resulting model is relatively simple, conserves mass, can fit complicated boundaries and yet is sufficiently flexible to permit local mesh refinements in areas of interest. Moreover, the simulation of the flooding and drying is included in a natural and straightforward manner. These features are illustrated by a test case for studies of convergence rates and by examples of flooding on a river plain and flow in a shallow estuary. Copyright ?? 2000 John Wiley & Sons, Ltd.

Parallel performance optimizations on unstructured mesh-based simulations

DOE PAGES

Sarje, Abhinav; Song, Sukhyun; Jacobsen, Douglas; ...

2015-06-01

This paper addresses two key parallelization challenges the unstructured mesh-based ocean modeling code, MPAS-Ocean, which uses a mesh based on Voronoi tessellations: (1) load imbalance across processes, and (2) unstructured data access patterns, that inhibit intra- and inter-node performance. Our work analyzes the load imbalance due to naive partitioning of the mesh, and develops methods to generate mesh partitioning with better load balance and reduced communication. Furthermore, we present methods that minimize both inter- and intranode data movement and maximize data reuse. Our techniques include predictive ordering of data elements for higher cache efficiency, as well as communication reduction approaches.more » We present detailed performance data when running on thousands of cores using the Cray XC30 supercomputer and show that our optimization strategies can exceed the original performance by over 2×. Additionally, many of these solutions can be broadly applied to a wide variety of unstructured grid-based computations.« less

Three-Dimensional High-Lift Analysis Using a Parallel Unstructured Multigrid Solver

NASA Technical Reports Server (NTRS)

Mavriplis, Dimitri J.

1998-01-01

A directional implicit unstructured agglomeration multigrid solver is ported to shared and distributed memory massively parallel machines using the explicit domain-decomposition and message-passing approach. Because the algorithm operates on local implicit lines in the unstructured mesh, special care is required in partitioning the problem for parallel computing. A weighted partitioning strategy is described which avoids breaking the implicit lines across processor boundaries, while incurring minimal additional communication overhead. Good scalability is demonstrated on a 128 processor SGI Origin 2000 machine and on a 512 processor CRAY T3E machine for reasonably fine grids. The feasibility of performing large-scale unstructured grid calculations with the parallel multigrid algorithm is demonstrated by computing the flow over a partial-span flap wing high-lift geometry on a highly resolved grid of 13.5 million points in approximately 4 hours of wall clock time on the CRAY T3E.

Computing Axisymmetric Jet Screech Tones Using Unstructured Grids

NASA Technical Reports Server (NTRS)

Jorgenson, Philip C. E.; Loh, Ching Y.

2002-01-01

The space-time conservation element and solution element (CE/SE) method is used to solve the conservation law form of the compressible axisymmetric Navier-Stokes equations. The equations are time marched to predict the unsteady flow and the near-field screech tone noise issuing from an underexpanded circular jet. The CE/SE method uses an unstructured grid based data structure. The unstructured grids for these calculations are generated based on the method of Delaunay triangulation. The purpose of this paper is to show that an acoustics solution with a feedback loop can be obtained using truly unstructured grid technology. Numerical results are presented for two different nozzle geometries. The first is considered to have a thin nozzle lip and the second has a thick nozzle lip. Comparisons with available experimental data are shown for flows corresponding to several different jet Mach numbers. Generally good agreement is obtained in terms of flow physics, screech tone frequency, and sound pressure level.

Quality factors and local adaption (with applications in Eulerian hydrodynamics)

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

Crowley, W.P.

1992-06-17

Adapting the mesh to suit the solution is a technique commonly used for solving both ode`s and pde`s. For Lagrangian hydrodynamics, ALE and Free-Lagrange are examples of structured and unstructured adaptive methods. For Eulerian hydrodynamics the two basic approaches are the macro-unstructuring technique pioneered by Oliger and Berger and the micro-structuring technique due to Lohner and others. Here we will describe a new micro-unstructuring technique, LAM, (for Local Adaptive Mesh) as applied to Eulerian hydrodynamics. The LAM technique consists of two independent parts: (1) the time advance scheme is a variation on the artificial viscosity method; (2) the adaption schememore » uses a micro-unstructured mesh with quadrilateral mesh elements. The adaption scheme makes use of quality factors and the relation between these and truncation errors is discussed. The time advance scheme; the adaption strategy; and the effect of different adaption parameters on numerical solutions are described.« less

Quality factors and local adaption (with applications in Eulerian hydrodynamics)

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

Crowley, W.P.

1992-06-17

Adapting the mesh to suit the solution is a technique commonly used for solving both ode's and pde's. For Lagrangian hydrodynamics, ALE and Free-Lagrange are examples of structured and unstructured adaptive methods. For Eulerian hydrodynamics the two basic approaches are the macro-unstructuring technique pioneered by Oliger and Berger and the micro-structuring technique due to Lohner and others. Here we will describe a new micro-unstructuring technique, LAM, (for Local Adaptive Mesh) as applied to Eulerian hydrodynamics. The LAM technique consists of two independent parts: (1) the time advance scheme is a variation on the artificial viscosity method; (2) the adaption schememore » uses a micro-unstructured mesh with quadrilateral mesh elements. The adaption scheme makes use of quality factors and the relation between these and truncation errors is discussed. The time advance scheme; the adaption strategy; and the effect of different adaption parameters on numerical solutions are described.« less

Inability of Prevotella bryantii to Form a Functional Shine-Dalgarno Interaction Reflects Unique Evolution of Ribosome Binding Sites in Bacteroidetes

PubMed Central

Accetto, Tomaž; Avguštin, Gorazd

2011-01-01

The Shine-Dalgarno (SD) sequence is a key element directing the translation to initiate at the authentic start codons and also enabling translation initiation to proceed in 5′ untranslated mRNA regions (5′-UTRs) containing moderately strong secondary structures. Bioinformatic analysis of almost forty genomes from the major bacterial phylum Bacteroidetes revealed, however, a general absence of SD sequence, drop in GC content and consequently reduced tendency to form secondary structures in 5′-UTRs. The experiments using the Prevotella bryantii TC1-1 expression system were in agreement with these findings: neither addition nor omission of SD sequence in the unstructured 5′-UTR affected the level of the reporter protein, non-specific nuclease NucB. Further, NucB level in P. bryantii TC1-1, contrary to hMGFP level in Escherichia coli, was five times lower when SD sequence formed part of the secondary structure with a folding energy -5,2 kcal/mol. Also, the extended SD sequences did not affect protein levels as in E. coli. It seems therefore that a functional SD interaction does not take place during the translation initiation in P. bryanttii TC1-1 and possibly other members of phylum Bacteroidetes although the anti SD sequence is present in 16S rRNA genes of their genomes. We thus propose that in the absence of the SD sequence interaction, the selection of genuine start codons in Bacteroidetes is accomplished by binding of ribosomal protein S1 to unstructured 5′-UTR as opposed to coding region which is inaccessible due to mRNA secondary structure. Additionally, we found that sequence logos of region preceding the start codons may be used as taxonomical markers. Depending on whether complete sequence logo or only part of it, such as information content and base proportion at specific positions, is used, bacterial genera or families and in some cases even bacterial phyla can be distinguished. PMID:21857964

On the role of residue phosphorylation in 14-3-3 partners: AANAT as a case study

PubMed Central

Masone, Diego; Uhart, Marina; Bustos, Diego M.

2017-01-01

Twenty years ago, a novel concept in protein structural biology was discovered: the intrinsically disordered regions (IDRs). These regions remain largely unstructured under native conditions and the more are studied, more properties are attributed to them. Possibly, one of the most important is their ability to conform a new type of protein-protein interaction. Besides the classical domain-to-domain interactions, IDRs follow a ‘fly-casting’ model including ‘induced folding’. Unfortunately, it is only possible to experimentally explore initial and final states. However, the complete movie of conformational changes of protein regions and their characterization can be addressed by in silico experiments. Here, we simulate the binding of two proteins to describe how the phosphorylation of a single residue modulates the entire process. 14-3-3 protein family is considered a master regulator of phosphorylated proteins and from a modern point-of-view, protein phosphorylation is a three component system, with writers (kinases), erasers (phosphatases) and readers. This later biological role is attributed to the 14-3-3 protein family. Our molecular dynamics results show that phosphorylation of the key residue Thr31 in a partner of 14-3-3, the aralkylamine N-acetyltransferase, releases the fly-casting mechanism during binding. On the other hand, the non-phosphorylation of the same residue traps the proteins, systematically and repeatedly driving the simulations into wrong protein-protein conformations. PMID:28387381

Characterisation of transition state structures for protein folding using 'high', 'medium' and 'low' {Phi}-values.

PubMed

Geierhaas, Christian D; Salvatella, Xavier; Clarke, Jane; Vendruscolo, Michele

2008-03-01

It has been suggested that Phi-values, which allow structural information about transition states (TSs) for protein folding to be obtained, are most reliably interpreted when divided into three classes (high, medium and low). High Phi-values indicate almost completely folded regions in the TS, intermediate Phi-values regions with a detectable amount of structure and low Phi-values indicate mostly unstructured regions. To explore the extent to which this classification can be used to characterise in detail the structure of TSs for protein folding, we used Phi-values divided into these classes as restraints in molecular dynamics simulations. This type of procedure is related to that used in NMR spectroscopy to define the structure of native proteins from the measurement of inter-proton distances derived from nuclear Overhauser effects. We illustrate this approach by determining the TS ensembles of five proteins and by showing that the results are similar to those obtained by using as restraints the actual numerical Phi-values measured experimentally. Our results indicate that the simultaneous consideration of a set of low-resolution Phi-values can provide sufficient information for characterising the architecture of a TS for folding of a protein.

Characterisation of transition state structures for protein folding using ‘high’, ‘medium’ and ‘low’ Φ-values

PubMed Central

Geierhaas, Christian D.; Salvatella, Xavier; Clarke, Jane; Vendruscolo, Michele

2008-01-01

It has been suggested that Φ-values, which allow structural information about transition states (TSs) for protein folding to be obtained, are most reliably interpreted when divided into three classes (high, medium and low). High Φ-values indicate almost completely folded regions in the TS, intermediate Φ-values regions with a detectable amount of structure and low Φ-values indicate mostly unstructured regions. To explore the extent to which this classification can be used to characterise in detail the structure of TSs for protein folding, we used Φ-values divided into these classes as restraints in molecular dynamics simulations. This type of procedure is related to that used in NMR spectroscopy to define the structure of native proteins from the measurement of inter-proton distances derived from nuclear Overhauser effects. We illustrate this approach by determining the TS ensembles of five proteins and by showing that the results are similar to those obtained by using as restraints the actual numerical Φ-values measured experimentally. Our results indicate that the simultaneous consideration of a set of low-resolution Φ-values can provide sufficient information for characterising the architecture of a TS for folding of a protein. PMID:18299294

The National Grid Project: A system overview

NASA Technical Reports Server (NTRS)

Gaither, Adam; Gaither, Kelly; Jean, Brian; Remotigue, Michael; Whitmire, John; Soni, Bharat; Thompson, Joe; Dannenhoffer,, John; Weatherill, Nigel

1995-01-01

The National Grid Project (NGP) is a comprehensive numerical grid generation software system that is being developed at the National Science Foundation (NSF) Engineering Research Center (ERC) for Computational Field Simulation (CFS) at Mississippi State University (MSU). NGP is supported by a coalition of U.S. industries and federal laboratories. The objective of the NGP is to significantly decrease the amount of time it takes to generate a numerical grid for complex geometries and to increase the quality of these grids to enable computational field simulations for applications in industry. A geometric configuration can be discretized into grids (or meshes) that have two fundamental forms: structured and unstructured. Structured grids are formed by intersecting curvilinear coordinate lines and are composed of quadrilateral (2D) and hexahedral (3D) logically rectangular cells. The connectivity of a structured grid provides for trivial identification of neighboring points by incrementing coordinate indices. Unstructured grids are composed of cells of any shape (commonly triangles, quadrilaterals, tetrahedra and hexahedra), but do not have trivial identification of neighbors by incrementing an index. For unstructured grids, a set of points and an associated connectivity table is generated to define unstructured cell shapes and neighboring points. Hybrid grids are a combination of structured grids and unstructured grids. Chimera (overset) grids are intersecting or overlapping structured grids. The NGP system currently provides a user interface that integrates both 2D and 3D structured and unstructured grid generation, a solid modeling topology data management system, an internal Computer Aided Design (CAD) system based on Non-Uniform Rational B-Splines (NURBS), a journaling language, and a grid/solution visualization system.

Using structured and unstructured data to identify patients' need for services that address the social determinants of health.

PubMed

Vest, Joshua R; Grannis, Shaun J; Haut, Dawn P; Halverson, Paul K; Menachemi, Nir

2017-11-01

Increasingly, health care providers are adopting population health management approaches that address the social determinants of health (SDH). However, effectively identifying patients needing services that address a SDH in primary care settings is challenging. The purpose of the current study is to explore how various data sources can identify adult primary care patients that are in need of services that address SDH. A cross-sectional study described patients in need of SDH services offered by a safety-net hospital's federally qualified health center clinics. SDH services of social work, behavioral health, nutrition counseling, respiratory therapy, financial planning, medical-legal partnership assistance, patient navigation, and pharmacist consultation were offered on a co-located basis and were identified using structured billing and scheduling data, and unstructured electronic health record data. We report the prevalence of the eight different SDH service needs and the patient characteristics associated with service need. Moreover, characteristics of patients with SDH services need documented in structured data sources were compared with those documented by unstructured data sources. More than half (53%) of patients needed SDH services. Those in need of such services tended to be female, older, more medically complex, and higher utilizers of services. Structured and unstructured data sources exhibited poor agreement on patient SDH services need. Patients with SDH services need documented by unstructured data tended to be more complex. The need for SDH services among a safety-net population is high. Identifying patients in need of such services requires multiple data sources with structured and unstructured data. Copyright © 2017. Published by Elsevier B.V.

The B7-1 Cytoplasmic Tail Enhances Intracellular Transport and Mammalian Cell Surface Display of Chimeric Proteins in the Absence of a Linear ER Export Motif

PubMed Central

Lin, Yi-Chieh; Chen, Bing-Mae; Lu, Wei-Cheng; Su, Chien-I; Prijovich, Zeljko M.; Chung, Wen-Chuan; Wu, Pei-Yu; Chen, Kai-Chuan; Lee, I-Chiao; Juan, Ting-Yi; Roffler, Steve R.

2013-01-01

Membrane-tethered proteins (mammalian surface display) are increasingly being used for novel therapeutic and biotechnology applications. Maximizing surface expression of chimeric proteins on mammalian cells is important for these applications. We show that the cytoplasmic domain from the B7-1 antigen, a commonly used element for mammalian surface display, can enhance the intracellular transport and surface display of chimeric proteins in a Sar1 and Rab1 dependent fashion. However, mutational, alanine scanning and deletion analysis demonstrate the absence of linear ER export motifs in the B7 cytoplasmic domain. Rather, efficient intracellular transport correlated with the presence of predicted secondary structure in the cytoplasmic tail. Examination of the cytoplasmic domains of 984 human and 782 mouse type I transmembrane proteins revealed that many previously identified ER export motifs are rarely found in the cytoplasmic tail of type I transmembrane proteins. Our results suggest that efficient intracellular transport of B7 chimeric proteins is associated with the structure rather than to the presence of a linear ER export motif in the cytoplasmic tail, and indicate that short (less than ~ 10-20 amino acids) and unstructured cytoplasmic tails should be avoided to express high levels of chimeric proteins on mammalian cells. PMID:24073236

EMPHASIS™/Nevada UTDEM User Guide Version 2.1.2

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

Turner, C. David; Pasik, Michael F.; Seidel, David B.

The Unstructured Time-Domain ElectroMagnetics (UTDEM) portion of the EMPHASIS suite solves Maxwell’s equations using finite-element techniques on unstructured meshes. This document provides user-specific information to facilitate the use of the code for applications of interest.

On Convergence Acceleration Techniques for Unstructured Meshes

NASA Technical Reports Server (NTRS)

Mavriplis, Dimitri J.

1998-01-01

A discussion of convergence acceleration techniques as they relate to computational fluid dynamics problems on unstructured meshes is given. Rather than providing a detailed description of particular methods, the various different building blocks of current solution techniques are discussed and examples of solution strategies using one or several of these ideas are given. Issues relating to unstructured grid CFD problems are given additional consideration, including suitability of algorithms to current hardware trends, memory and cpu tradeoffs, treatment of non-linearities, and the development of efficient strategies for handling anisotropy-induced stiffness. The outlook for future potential improvements is also discussed.

Wind-US Unstructured Flow Solutions for a Transonic Diffuser

NASA Technical Reports Server (NTRS)

Mohler, Stanley R., Jr.

2005-01-01

The Wind-US Computational Fluid Dynamics flow solver computed flow solutions for a transonic diffusing duct. The calculations used an unstructured (hexahedral) grid. The Spalart-Allmaras turbulence model was used. Static pressures along the upper and lower wall agreed well with experiment, as did velocity profiles. The effect of the smoothing input parameters on convergence and solution accuracy was investigated. The meaning and proper use of these parameters are discussed for the benefit of Wind-US users. Finally, the unstructured solver is compared to the structured solver in terms of run times and solution accuracy.

Insight into a novel p53 single point mutation (G389E) by Molecular Dynamics Simulations.

PubMed

Pirolli, Davide; Carelli Alinovi, Cristiana; Capoluongo, Ettore; Satta, Maria Antonia; Concolino, Paola; Giardina, Bruno; De Rosa, Maria Cristina

2010-12-30

The majority of inactivating mutations of p53 reside in the central core DNA binding domain of the protein. In this computational study, we investigated the structural effects of a novel p53 mutation (G389E), identified in a patient with congenital adrenal hyperplasia, which is located within the extreme C-terminal domain (CTD) of p53, an unstructured, flexible region (residues 367-393) of major importance for the regulation of the protein. Based on the three-dimensional structure of a carboxyl-terminal peptide of p53 in complex with the S100B protein, which is involved in regulation of the tumor suppressor activity, a model of wild type (WT) and mutant extreme CTD was developed by molecular modeling and molecular dynamics simulation. It was found that the G389E amino acid replacement has negligible effects on free p53 in solution whereas it significantly affects the interactions of p53 with the S100B protein. The results suggest that the observed mutation may interfere with p53 transcription activation and provide useful information for site-directed mutagenesis experiments.

Simulation of FRET dyes allows quantitative comparison against experimental data

NASA Astrophysics Data System (ADS)

Reinartz, Ines; Sinner, Claude; Nettels, Daniel; Stucki-Buchli, Brigitte; Stockmar, Florian; Panek, Pawel T.; Jacob, Christoph R.; Nienhaus, Gerd Ulrich; Schuler, Benjamin; Schug, Alexander

2018-03-01

Fully understanding biomolecular function requires detailed insight into the systems' structural dynamics. Powerful experimental techniques such as single molecule Förster Resonance Energy Transfer (FRET) provide access to such dynamic information yet have to be carefully interpreted. Molecular simulations can complement these experiments but typically face limits in accessing slow time scales and large or unstructured systems. Here, we introduce a coarse-grained simulation technique that tackles these challenges. While requiring only few parameters, we maintain full protein flexibility and include all heavy atoms of proteins, linkers, and dyes. We are able to sufficiently reduce computational demands to simulate large or heterogeneous structural dynamics and ensembles on slow time scales found in, e.g., protein folding. The simulations allow for calculating FRET efficiencies which quantitatively agree with experimentally determined values. By providing atomically resolved trajectories, this work supports the planning and microscopic interpretation of experiments. Overall, these results highlight how simulations and experiments can complement each other leading to new insights into biomolecular dynamics and function.

Extension of in vivo half-life of biologically active peptides via chemical conjugation to XTEN protein polymer.

PubMed

Podust, Vladimir N; Sim, Bee-Cheng; Kothari, Dharti; Henthorn, Lana; Gu, Chen; Wang, Chia-wei; McLaughlin, Bryant; Schellenberger, Volker

2013-11-01

XTEN, unstructured biodegradable proteins, have been used to extend the in vivo half-life of genetically fused therapeutic proteins and peptides. To expand the applications of XTEN technology to half-life extension of other classes of molecules, XTEN protein polymers and methods for chemical XTENylation were developed. Two XTEN precursors were engineered to contain enzymatically removable purification tags. The proteins were readily expressed in bacteria and purified to homogeneity by chromatography techniques. As proof-of-principle, GLP2-2G peptide was chemically conjugated to each of the two XTEN protein polymers using maleimide-thiol chemistry. The monodisperse nature of XTEN protein polymer enabled reaction monitoring as well as the detection of peptide modifications in the conjugated state using reverse phase-high performance liquid chromatography (RP-HPLC) and electrospray ionization mass spectrometry. The resulting GLP2-2G-XTEN conjugates were purified by preparative RP-HPLC to homogeneity. In comparison with recombinantly fused GLP2-2G-XTEN, chemically conjugated GLP2-2G-XTEN molecules exhibited comparable in vitro activity, in vitro plasma stability and pharmacokinetics in rats. These data suggest that chemical XTENylation could effectively extend the half-life of a wide spectrum of biologically active molecules, therefore broadening its applicability.

Structured and Unstructured Learning.

ERIC Educational Resources Information Center

1996

This document contains four papers presented at a sympoisum on structured and unstructured learning moderated by Catherine Sleezer at the 1996 conference of the Academy of Human Resource Development (AHRD). "Designing Experiential Learning into Organizational Work Life: Proposing a Framework for Theory and Research" (Cheri Maben-Crouch)…

Security Aspects of Computer Supported Collaborative Work

DTIC Science & Technology

1993-09-01

unstructured tasks at one end 11 and prescriptive tasks at the other. Unstructured tasks are those requiring creative input from a number of users and...collaborative technology begun to mature, it has begun to outstrip prevailing management attitudes. One barrier to telecommuting is the perception that

Parallel Performance Optimizations on Unstructured Mesh-based Simulations

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

Sarje, Abhinav; Song, Sukhyun; Jacobsen, Douglas

2015-01-01

© The Authors. Published by Elsevier B.V. This paper addresses two key parallelization challenges the unstructured mesh-based ocean modeling code, MPAS-Ocean, which uses a mesh based on Voronoi tessellations: (1) load imbalance across processes, and (2) unstructured data access patterns, that inhibit intra- and inter-node performance. Our work analyzes the load imbalance due to naive partitioning of the mesh, and develops methods to generate mesh partitioning with better load balance and reduced communication. Furthermore, we present methods that minimize both inter- and intranode data movement and maximize data reuse. Our techniques include predictive ordering of data elements for higher cachemore » efficiency, as well as communication reduction approaches. We present detailed performance data when running on thousands of cores using the Cray XC30 supercomputer and show that our optimization strategies can exceed the original performance by over 2×. Additionally, many of these solutions can be broadly applied to a wide variety of unstructured grid-based computations.« less

Application of an Unstructured Grid Navier-Stokes Solver to a Generic Helicopter Boby: Comparison of Unstructured Grid Results with Structured Grid Results and Experimental Results

NASA Technical Reports Server (NTRS)

Mineck, Raymond E.

1999-01-01

An unstructured-grid Navier-Stokes solver was used to predict the surface pressure distribution, the off-body flow field, the surface flow pattern, and integrated lift and drag coefficients on the ROBIN configuration (a generic helicopter) without a rotor at four angles of attack. The results are compared to those predicted by two structured- grid Navier-Stokes solvers and to experimental surface pressure distributions. The surface pressure distributions from the unstructured-grid Navier-Stokes solver are in good agreement with the results from the structured-grid Navier-Stokes solvers. Agreement with the experimental pressure coefficients is good over the forward portion of the body. However, agreement is poor on the lower portion of the mid-section of the body. Comparison of the predicted surface flow patterns showed similar regions of separated flow. Predicted lift and drag coefficients were in fair agreement with each other.

Computing Flows Using Chimera and Unstructured Grids

NASA Technical Reports Server (NTRS)

Liou, Meng-Sing; Zheng, Yao

2006-01-01

DRAGONFLOW is a computer program that solves the Navier-Stokes equations of flows in complexly shaped three-dimensional regions discretized by use of a direct replacement of arbitrary grid overlapping by nonstructured (DRAGON) grid. A DRAGON grid (see figure) is a combination of a chimera grid (a composite of structured subgrids) and a collection of unstructured subgrids. DRAGONFLOW incorporates modified versions of two prior Navier-Stokes-equation-solving programs: OVERFLOW, which is designed to solve on chimera grids; and USM3D, which is used to solve on unstructured grids. A master module controls the invocation of individual modules in the libraries. At each time step of a simulated flow, DRAGONFLOW is invoked on the chimera portion of the DRAGON grid in alternation with USM3D, which is invoked on the unstructured subgrids of the DRAGON grid. The USM3D and OVERFLOW modules then immediately exchange their solutions and other data. As a result, USM3D and OVERFLOW are coupled seamlessly.

The design and implementation of a parallel unstructured Euler solver using software primitives

NASA Technical Reports Server (NTRS)

Das, R.; Mavriplis, D. J.; Saltz, J.; Gupta, S.; Ponnusamy, R.

1992-01-01

This paper is concerned with the implementation of a three-dimensional unstructured grid Euler-solver on massively parallel distributed-memory computer architectures. The goal is to minimize solution time by achieving high computational rates with a numerically efficient algorithm. An unstructured multigrid algorithm with an edge-based data structure has been adopted, and a number of optimizations have been devised and implemented in order to accelerate the parallel communication rates. The implementation is carried out by creating a set of software tools, which provide an interface between the parallelization issues and the sequential code, while providing a basis for future automatic run-time compilation support. Large practical unstructured grid problems are solved on the Intel iPSC/860 hypercube and Intel Touchstone Delta machine. The quantitative effect of the various optimizations are demonstrated, and we show that the combined effect of these optimizations leads to roughly a factor of three performance improvement. The overall solution efficiency is compared with that obtained on the CRAY-YMP vector supercomputer.

Coacervates of lactotransferrin and β- or κ-casein: structure determined using SAXS.

PubMed

de Kruif, C G Kees; Pedersen, JanSkov; Huppertz, Thom; Anema, Skelte G

2013-08-20

Lactotransferrin (LF) is a large globular protein in milk with immune-regulatory and bactericidal properties. At pH 6.5, LF (M = 78 kDa) carries a net (calculated) charge of +21. β-Casein (BCN) and κ-casein (KCN) are part of the casein micelle complex in milk. Both BCN and KCN are amphiphillic proteins with a molar mass of 24 and 19 kDa and carry net charges of -14 and -4, respectively. Both BCN and KCN form soap-like micelles, with 40 and 65 monomers, respectively. The net negative charges are located in the corona of the micelles. On mixing LF with the caseins, coacervates are formed. We analyzed the structure of these coarcervates using SAXS. It was found that LF binds to the corona of the micellar structures, at the charge neutrality point. BCN/LF and KCN/LF ratios at the charge neutrality point were found to be ~1.2 and ~5, respectively. We think that the findings are relevant for the protection mechanism of globular proteins in bodily fluids where unstructured proteins are abundant (saliva). The complexes will prevent docking of enzymes on specific charged groups on the globular protein.

Protein domain definition should allow for conditional disorder

PubMed Central

Yegambaram, Kavestri; Bulloch, Esther MM; Kingston, Richard L

2013-01-01

Abstract: Proteins are often classified in a binary fashion as either structured or disordered. However this approach has several deficits. Firstly, protein folding is always conditional on the physiochemical environment. A protein which is structured in some circumstances will be disordered in others. Secondly, it hides a fundamental asymmetry in behavior. While all structured proteins can be unfolded through a change in environment, not all disordered proteins have the capacity for folding. Failure to accommodate these complexities confuses the definition of both protein structural domains and intrinsically disordered regions. We illustrate these points with an experimental study of a family of small binding domains, drawn from the RNA polymerase of mumps virus and its closest relatives. Assessed at face value the domains fall on a structural continuum, with folded, partially folded, and near unstructured members. Yet the disorder present in the family is conditional, and these closely related polypeptides can access the same folded state under appropriate conditions. Any heuristic definition of the protein domain emphasizing conformational stability divides this domain family in two, in a way that makes no biological sense. Structural domains would be better defined by their ability to adopt a specific tertiary structure: a structure that may or may not be realized, dependent on the circumstances. This explicitly allows for the conditional nature of protein folding, and more clearly demarcates structural domains from intrinsically disordered regions that may function without folding. PMID:23963781

Bracketing as a skill in conducting unstructured qualitative interviews.

PubMed

Sorsa, Minna Anneli; Kiikkala, Irma; Åstedt-Kurki, Päivi

2015-03-01

To provide an overview of bracketing as a skill in unstructured qualitative research interviews. Researchers affect the qualitative research process. Bracketing in descriptive phenomenology entails researchers setting aside their pre-understanding and acting non-judgementally. In interpretative phenomenology, previous knowledge is used intentionally to create new understanding. A literature search of bracketing in phenomenology and qualitative research. This is a methodology paper examining the researchers' impact in creating data in creating data in qualitative research. Self-knowledge, sensitivity and reflexivity of the researcher enable bracketing. Skilled and experienced researchers are needed to use bracketing in unstructured qualitative research interviews. Bracketing adds scientific rigour and validity to any qualitative study.

A Solution Adaptive Structured/Unstructured Overset Grid Flow Solver with Applications to Helicopter Rotor Flows

NASA Technical Reports Server (NTRS)

Duque, Earl P. N.; Biswas, Rupak; Strawn, Roger C.

1995-01-01

This paper summarizes a method that solves both the three dimensional thin-layer Navier-Stokes equations and the Euler equations using overset structured and solution adaptive unstructured grids with applications to helicopter rotor flowfields. The overset structured grids use an implicit finite-difference method to solve the thin-layer Navier-Stokes/Euler equations while the unstructured grid uses an explicit finite-volume method to solve the Euler equations. Solutions on a helicopter rotor in hover show the ability to accurately convect the rotor wake. However, isotropic subdivision of the tetrahedral mesh rapidly increases the overall problem size.

Modeling dam-break flows using finite volume method on unstructured grid

USDA-ARS?s Scientific Manuscript database

Two-dimensional shallow water models based on unstructured finite volume method and approximate Riemann solvers for computing the intercell fluxes have drawn growing attention because of their robustness, high adaptivity to complicated geometry and ability to simulate flows with mixed regimes and di...

The 3-D unstructured mesh generation using local transformations

NASA Technical Reports Server (NTRS)

Barth, Timothy J.

1993-01-01

The topics are presented in viewgraph form and include the following: 3D combinatorial edge swapping; 3D incremental triangulation via local transformations; a new approach to multigrid for unstructured meshes; surface mesh generation using local transforms; volume triangulations; viscous mesh generation; and future directions.

36 CFR 1236.24 - What are the additional requirements for managing unstructured electronic records?

Code of Federal Regulations, 2012 CFR

2012-07-01

... requirements for managing unstructured electronic records? 1236.24 Section 1236.24 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION RECORDS MANAGEMENT ELECTRONIC RECORDS MANAGEMENT Additional Requirements for Electronic Records § 1236.24 What are the additional requirements for managing...

36 CFR 1236.24 - What are the additional requirements for managing unstructured electronic records?

Code of Federal Regulations, 2010 CFR

2010-07-01

... requirements for managing unstructured electronic records? 1236.24 Section 1236.24 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION RECORDS MANAGEMENT ELECTRONIC RECORDS MANAGEMENT Additional Requirements for Electronic Records § 1236.24 What are the additional requirements for managing...

36 CFR 1236.24 - What are the additional requirements for managing unstructured electronic records?

Code of Federal Regulations, 2011 CFR

2011-07-01

... requirements for managing unstructured electronic records? 1236.24 Section 1236.24 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION RECORDS MANAGEMENT ELECTRONIC RECORDS MANAGEMENT Additional Requirements for Electronic Records § 1236.24 What are the additional requirements for managing...

36 CFR 1236.24 - What are the additional requirements for managing unstructured electronic records?

Code of Federal Regulations, 2014 CFR

2014-07-01

... requirements for managing unstructured electronic records? 1236.24 Section 1236.24 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION RECORDS MANAGEMENT ELECTRONIC RECORDS MANAGEMENT Additional Requirements for Electronic Records § 1236.24 What are the additional requirements for managing...

Classification of pregnancies of unknown location according to four different hCG-based protocols.

PubMed

Fistouris, J; Bergh, C; Strandell, A

2016-10-01

How do four protocols based on serial human chorionic gonadotropin (hCG) measurements perform when classifying pregnancies of unknown location (PULs) as low or high risk of being an ectopic pregnancy (EP)? The use of cut-offs in hCG level changes published by NICE, and a logistic regression model, M4, correctly classify more PULs as high risk, compared with two other protocols. A logistic regression model, M4, based on the mean of two consecutive hCG values and the hCG ratio (hCG 48 h/hCG 0 h) that classify PULs into low- and high-risk groups for triage purposes, identifies more EPs than a protocol using the cut-offs between a 13% decline and a 66% rise in hCG levels over 48 h. A retrospective comparative study of four different hCG-based protocols classifying PULs as low or high risk of being an EP was performed at a gynaecological emergency unit over 3 years. We identified 915 women with a PUL. Initial transvaginal ultrasonography (TVS) findings categorised 187 of the PULs as probable intrauterine pregnancies (IUPs) and 16 as probable EPs. The rate of change in hCG levels over 48 h was calculated for each patient and subjected to three different hCG threshold intervals and a logistic regression model for outcome prediction. Each PUL was subsequently dichotomised to either low-risk (i.e. failed PUL/IUP) or high-risk (i.e. EP) classification, which allowed us to compare the diagnostic performance. In 'Protocol A', a PUL was classified as low risk if >13% hCG level decline or >66% hCG level rise was achieved; otherwise, the PUL was classified as high risk of being an EP. 'Protocol B' classified a PUL as low or high risk using cut-offs of 35-50% declining hCG levels and of 53% rising hCG levels. Similarly, 'Protocol C' used hCG level cut-offs published by NICE, 50% for declining hCG levels and 63% for rising hCG levels. Finally, if a logistic regression model 'Protocol M4' calculated a ≥5% risk of the PUL being an EP, it was classified as high risk, and otherwise the PUL was classified as low risk. When the time interval between two hCG measurements failed to meet an exact 48 h, extrapolation and interpolation of hCG values was made, using log linear transformation. Protocols A, B, C and M4 classified 73, 66, 55 and 56% of PULs as low risk. The sensitivity for protocols A, B, C and M4 was 68% (95% confidence interval (CI) 61-75%), 81% (74-86%), 87% (82-92%) and 88% (83-93%), respectively. The specificity was 82% (80-85%), 77% (74-80%), 66% (62-69%) and 67% (63-70%) for protocols A, B, C and M4, respectively. All comparisons of sensitivity and specificity between the protocols were statistically significant except for protocol C versus protocol M4. In protocol C, 87% (66-97%) of misclassified EPs had rising hCG levels, compared with 19% (6-41%) for protocol M4 (P < 0.01). In a secondary analysis excluding probable IUPs and probable EPs, the results for 712 PULs were analysed. The sensitivity subsequently remained stable for all protocols. Protocol M4 reached a 78% (74-81%) specificity, which was significantly higher than 70% (66-74%) for protocol C (P = 0.01) and protocol M4 classified 63% of PULs as low risk compared with 58% for protocol C. The retrospective design of the study is a limitation. The results are derived from a population where laparoscopy played an important role in PUL management and diagnosis of EPs, although it did reflect real clinical practice. Although we tried to adhere to definitions of PUL and final outcomes as in previous studies and a recent consensus statement, potential differences in this regard must be acknowledged. Where the time interval between two serial hCG measurements deviated from 48 h we estimated 48 h hCG values. A logistic regression model, M4, classifies more PULs correctly as low risk in a selected PUL population without probable IUPs and EPs and identifies as many EPs, in comparison with the cut-offs available in the NICE guideline. This advantage for model M4 may result in a reduction of unnecessary follow-up visits, when fewer low-risk PULs are misclassified as high risk. These findings, however, ought to be clarified in a randomised controlled trial. The study was supported by LUA/ALF grant No. 70940. There are no competing interests. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Two novel heat-soluble protein families abundantly expressed in an anhydrobiotic tardigrade.

PubMed

Yamaguchi, Ayami; Tanaka, Sae; Yamaguchi, Shiho; Kuwahara, Hirokazu; Takamura, Chizuko; Imajoh-Ohmi, Shinobu; Horikawa, Daiki D; Toyoda, Atsushi; Katayama, Toshiaki; Arakawa, Kazuharu; Fujiyama, Asao; Kubo, Takeo; Kunieda, Takekazu

2012-01-01

Tardigrades are able to tolerate almost complete dehydration by reversibly switching to an ametabolic state. This ability is called anhydrobiosis. In the anhydrobiotic state, tardigrades can withstand various extreme environments including space, but their molecular basis remains largely unknown. Late embryogenesis abundant (LEA) proteins are heat-soluble proteins and can prevent protein-aggregation in dehydrated conditions in other anhydrobiotic organisms, but their relevance to tardigrade anhydrobiosis is not clarified. In this study, we focused on the heat-soluble property characteristic of LEA proteins and conducted heat-soluble proteomics using an anhydrobiotic tardigrade. Our heat-soluble proteomics identified five abundant heat-soluble proteins. All of them showed no sequence similarity with LEA proteins and formed two novel protein families with distinct subcellular localizations. We named them Cytoplasmic Abundant Heat Soluble (CAHS) and Secretory Abundant Heat Soluble (SAHS) protein families, according to their localization. Both protein families were conserved among tardigrades, but not found in other phyla. Although CAHS protein was intrinsically unstructured and SAHS protein was rich in β-structure in the hydrated condition, proteins in both families changed their conformation to an α-helical structure in water-deficient conditions as LEA proteins do. Two conserved repeats of 19-mer motifs in CAHS proteins were capable to form amphiphilic stripes in α-helices, suggesting their roles as molecular shield in water-deficient condition, though charge distribution pattern in α-helices were different between CAHS and LEA proteins. Tardigrades might have evolved novel protein families with a heat-soluble property and this study revealed a novel repertoire of major heat-soluble proteins in these anhydrobiotic animals.

A multidimensional unified gas-kinetic scheme for radiative transfer equations on unstructured mesh

NASA Astrophysics Data System (ADS)

Sun, Wenjun; Jiang, Song; Xu, Kun

2017-12-01

In order to extend the unified gas kinetic scheme (UGKS) to solve radiative transfer equations in a complex geometry, a multidimensional asymptotic preserving implicit method on unstructured mesh is constructed in this paper. With an implicit formulation, the CFL condition for the determination of the time step in UGKS can be much relaxed, and a large time step is used in simulations. Differently from previous direction-by-direction UGKS on orthogonal structured mesh, on unstructured mesh the interface flux transport takes into account multi-dimensional effect, where gradients of radiation intensity and material temperature in both normal and tangential directions of a cell interface are included in the flux evaluation. The multiple scale nature makes the UGKS be able to capture the solutions in both optically thin and thick regions seamlessly. In the optically thick region the condition of cell size being less than photon's mean free path is fully removed, and the UGKS recovers a solver for diffusion equation in such a limit on unstructured mesh. For a distorted quadrilateral mesh, the UGKS goes to a nine-point scheme for the diffusion equation, and it naturally reduces to the standard five-point scheme for a orthogonal quadrilateral mesh. Numerical computations covering a wide range of transport regimes on unstructured and distorted quadrilateral meshes will be presented to validate the current approach.

Out-of-Core Streamline Visualization on Large Unstructured Meshes

NASA Technical Reports Server (NTRS)

Ueng, Shyh-Kuang; Sikorski, K.; Ma, Kwan-Liu

1997-01-01

It's advantageous for computational scientists to have the capability to perform interactive visualization on their desktop workstations. For data on large unstructured meshes, this capability is not generally available. In particular, particle tracing on unstructured grids can result in a high percentage of non-contiguous memory accesses and therefore may perform very poorly with virtual memory paging schemes. The alternative of visualizing a lower resolution of the data degrades the original high-resolution calculations. This paper presents an out-of-core approach for interactive streamline construction on large unstructured tetrahedral meshes containing millions of elements. The out-of-core algorithm uses an octree to partition and restructure the raw data into subsets stored into disk files for fast data retrieval. A memory management policy tailored to the streamline calculations is used such that during the streamline construction only a very small amount of data are brought into the main memory on demand. By carefully scheduling computation and data fetching, the overhead of reading data from the disk is significantly reduced and good memory performance results. This out-of-core algorithm makes possible interactive streamline visualization of large unstructured-grid data sets on a single mid-range workstation with relatively low main-memory capacity: 5-20 megabytes. Our test results also show that this approach is much more efficient than relying on virtual memory and operating system's paging algorithms.

JIGSAW-GEO (1.0): Locally Orthogonal Staggered Unstructured Grid Generation for General Circulation Modelling on the Sphere

NASA Technical Reports Server (NTRS)

Engwirda, Darren

2017-01-01

An algorithm for the generation of non-uniform, locally orthogonal staggered unstructured spheroidal grids is described. This technique is designed to generate very high-quality staggered VoronoiDelaunay meshes appropriate for general circulation modelling on the sphere, including applications to atmospheric simulation, ocean-modelling and numerical weather prediction. Using a recently developed Frontal-Delaunay refinement technique, a method for the construction of high-quality unstructured spheroidal Delaunay triangulations is introduced. A locally orthogonal polygonal grid, derived from the associated Voronoi diagram, is computed as the staggered dual. It is shown that use of the Frontal-Delaunay refinement technique allows for the generation of very high-quality unstructured triangulations, satisfying a priori bounds on element size and shape. Grid quality is further improved through the application of hill-climbing-type optimisation techniques. Overall, the algorithm is shown to produce grids with very high element quality and smooth grading characteristics, while imposing relatively low computational expense. A selection of uniform and non-uniform spheroidal grids appropriate for high-resolution, multi-scale general circulation modelling are presented. These grids are shown to satisfy the geometric constraints associated with contemporary unstructured C-grid-type finite-volume models, including the Model for Prediction Across Scales (MPAS-O). The use of user-defined mesh-spacing functions to generate smoothly graded, non-uniform grids for multi-resolution-type studies is discussed in detail.

JIGSAW-GEO (1.0): locally orthogonal staggered unstructured grid generation for general circulation modelling on the sphere

NASA Astrophysics Data System (ADS)

Engwirda, Darren

2017-06-01

An algorithm for the generation of non-uniform, locally orthogonal staggered unstructured spheroidal grids is described. This technique is designed to generate very high-quality staggered Voronoi-Delaunay meshes appropriate for general circulation modelling on the sphere, including applications to atmospheric simulation, ocean-modelling and numerical weather prediction. Using a recently developed Frontal-Delaunay refinement technique, a method for the construction of high-quality unstructured spheroidal Delaunay triangulations is introduced. A locally orthogonal polygonal grid, derived from the associated Voronoi diagram, is computed as the staggered dual. It is shown that use of the Frontal-Delaunay refinement technique allows for the generation of very high-quality unstructured triangulations, satisfying a priori bounds on element size and shape. Grid quality is further improved through the application of hill-climbing-type optimisation techniques. Overall, the algorithm is shown to produce grids with very high element quality and smooth grading characteristics, while imposing relatively low computational expense. A selection of uniform and non-uniform spheroidal grids appropriate for high-resolution, multi-scale general circulation modelling are presented. These grids are shown to satisfy the geometric constraints associated with contemporary unstructured C-grid-type finite-volume models, including the Model for Prediction Across Scales (MPAS-O). The use of user-defined mesh-spacing functions to generate smoothly graded, non-uniform grids for multi-resolution-type studies is discussed in detail.

Unstructured mesh adaptivity for urban flooding modelling

NASA Astrophysics Data System (ADS)

Hu, R.; Fang, F.; Salinas, P.; Pain, C. C.

2018-05-01

Over the past few decades, urban floods have been gaining more attention due to their increase in frequency. To provide reliable flooding predictions in urban areas, various numerical models have been developed to perform high-resolution flood simulations. However, the use of high-resolution meshes across the whole computational domain causes a high computational burden. In this paper, a 2D control-volume and finite-element flood model using adaptive unstructured mesh technology has been developed. This adaptive unstructured mesh technique enables meshes to be adapted optimally in time and space in response to the evolving flow features, thus providing sufficient mesh resolution where and when it is required. It has the advantage of capturing the details of local flows and wetting and drying front while reducing the computational cost. Complex topographic features are represented accurately during the flooding process. For example, the high-resolution meshes around the buildings and steep regions are placed when the flooding water reaches these regions. In this work a flooding event that happened in 2002 in Glasgow, Scotland, United Kingdom has been simulated to demonstrate the capability of the adaptive unstructured mesh flooding model. The simulations have been performed using both fixed and adaptive unstructured meshes, and then results have been compared with those published 2D and 3D results. The presented method shows that the 2D adaptive mesh model provides accurate results while having a low computational cost.

Unsupervised Ontology Generation from Unstructured Text. CRESST Report 827

ERIC Educational Resources Information Center

Mousavi, Hamid; Kerr, Deirdre; Iseli, Markus R.

2013-01-01

Ontologies are a vital component of most knowledge acquisition systems, and recently there has been a huge demand for generating ontologies automatically since manual or supervised techniques are not scalable. In this paper, we introduce "OntoMiner", a rule-based, iterative method to extract and populate ontologies from unstructured or…

Marathon Group Therapy with Female Narcotic Addicts.

ERIC Educational Resources Information Center

Kilmann, Peter R.

This study evaluated the impact of structured and unstructured marathon therapy on institutionalized female narcotic addicts. Subjects were randomly assigned to one of five groups: two structured therapy groups, two unstructured therapy groups, and a no-treatment control group. The Personal Orientation Inventory, the Adjective Check List, and a…

Imaging diagnosis--pulmonary metastases in New World camelids.

PubMed

Gall, David A; Zekas, Lisa J; Van Metre, David; Holt, Timothy

2006-01-01

The radiographic appearance of pulmonary metastatic disease from carcinoma is described in a llama and an alpaca. In one, a diffuse miliary pattern was seen. In the other, a more atypical unstructured interstitial pattern was recognized. Metastatic pulmonary neoplasia in camelids may assume a generalized miliary or unstructured pattern.

[Hand transplantation and implantation of nerve chips. New developments within hand surgery].

PubMed

Dahlin, L; Fridén, J; Hagberg, L; Lundborg, G

2000-03-20

Injuries and diseases of the hand naturally have an enormous impact on hand function and on quality of life, both occupational and social. The majority of hand-injury patients are under 30 years of age. Hand surgery, an established specialty in Sweden since 1969, is of great importance in terms of clinical developments, education and research. In the coming decade, scientific and clinical advances are to be expected in several fields such as nerve injuries including brachial plexus lesion, microsurgery, flexor tendon injuries and tendon transfer. Bioimplant research and new advances at the biotechnological interface will yield new options in nerve reconstruction, microchip implants in the nervous system, and the restoration of muscle-tendon function following injury. Artificial limbs with advanced motor and sensory functions will be important future aids in the rehabilitation of amputees. Transplantation of human hands is another promising reconstructive procedure which may open iup new perspectives in the coming millennium.

Aggregation propensity of critical regions of the protein Tau

NASA Astrophysics Data System (ADS)

Muthee, Micaiah; Ahmed, Azka; Larini, Luca

The Alzheimer's disease is an irreversible, progressive brain disorder that slowly destroys memory and thinking skills, which eventually leads to the ability to not able to carry out the simplest tasks. The Alzheimer's disease is characterized by the formation of protein aggregates both within and outside of the brain's cells, the neurons. Within the neurons, the aggregation of the protein tau leads to the destruction of the microtubules in the axon of the neuron. Tau belongs to a group of proteins referred to as Microtubule-Associated Proteins. It is extremely flexible and is classified as an intrinsically unstructured protein due to its low propensity to form secondary structure. Tau promotes tubulin assembly into microtubules thereby stabilizing the cytoskeleton of the axon of the neurons. The microtubule binding region of tau consists of 4 pseudo-repeats. In this study, we will focus on the aggregation propensity of two fragments. In this study we will focus on the PHF43 fragment that contains the third pseudo-repeat and has been shown experimentally to aggregate readily. Another fragment that contains the second pseudo-repeat will be considered as well. Mutations in this region are associated with various form of dementia and for this reason we will consider the mutant P301L.

The FOXP2 forkhead domain binds to a variety of DNA sequences with different rates and affinities.

PubMed

Webb, Helen; Steeb, Olga; Blane, Ashleigh; Rotherham, Lia; Aron, Shaun; Machanick, Philip; Dirr, Heini; Fanucchi, Sylvia

2017-07-01

FOXP2 is a member of the P subfamily of FOX transcription factors, the DNA-binding domain of which is the winged helix forkhead domain (FHD). In this work we show that the FOXP2 FHD is able to bind to various DNA sequences, including a novel sequence identified in this work, with different affinities and rates as detected using surface plasmon resonance. Combining the experimental work with molecular docking, we show that high-affinity sequences remain bound to the protein for longer, form a greater number of interactions with the protein and induce a greater structural change in the protein than low-affinity sequences. We propose a binding model for the FOXP2 FHD that involves three types of binding sequence: low affinity sites which allow for rapid scanning of the genome by the protein in a partially unstructured state; moderate affinity sites which serve to locate the protein near target sites and high-affinity sites which secure the protein to the DNA and induce a conformational change necessary for functional binding and the possible initiation of downstream transcriptional events. © The Authors 2017. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Functional specificity of a Hox protein mediated by the recognition of minor groove structure.

PubMed

Joshi, Rohit; Passner, Jonathan M; Rohs, Remo; Jain, Rinku; Sosinsky, Alona; Crickmore, Michael A; Jacob, Vinitha; Aggarwal, Aneel K; Honig, Barry; Mann, Richard S

2007-11-02

The recognition of specific DNA-binding sites by transcription factors is a critical yet poorly understood step in the control of gene expression. Members of the Hox family of transcription factors bind DNA by making nearly identical major groove contacts via the recognition helices of their homeodomains. In vivo specificity, however, often depends on extended and unstructured regions that link Hox homeodomains to a DNA-bound cofactor, Extradenticle (Exd). Using a combination of structure determination, computational analysis, and in vitro and in vivo assays, we show that Hox proteins recognize specific Hox-Exd binding sites via residues located in these extended regions that insert into the minor groove but only when presented with the correct DNA sequence. Our results suggest that these residues, which are conserved in a paralog-specific manner, confer specificity by recognizing a sequence-dependent DNA structure instead of directly reading a specific DNA sequence.

Conserved Sequence Preferences Contribute to Substrate Recognition by the Proteasome*

PubMed Central

Yu, Houqing; Singh Gautam, Amit K.; Wilmington, Shameika R.; Wylie, Dennis; Martinez-Fonts, Kirby; Kago, Grace; Warburton, Marie; Chavali, Sreenivas; Inobe, Tomonao; Finkelstein, Ilya J.; Babu, M. Madan

2016-01-01

The proteasome has pronounced preferences for the amino acid sequence of its substrates at the site where it initiates degradation. Here, we report that modulating these sequences can tune the steady-state abundance of proteins over 2 orders of magnitude in cells. This is the same dynamic range as seen for inducing ubiquitination through a classic N-end rule degron. The stability and abundance of His3 constructs dictated by the initiation site affect survival of yeast cells and show that variation in proteasomal initiation can affect fitness. The proteasome's sequence preferences are linked directly to the affinity of the initiation sites to their receptor on the proteasome and are conserved between Saccharomyces cerevisiae, Schizosaccharomyces pombe, and human cells. These findings establish that the sequence composition of unstructured initiation sites influences protein abundance in vivo in an evolutionarily conserved manner and can affect phenotype and fitness. PMID:27226608

Progress Toward Overset-Grid Moving Body Capability for USM3D Unstructured Flow Solver

NASA Technical Reports Server (NTRS)

Pandyna, Mohagna J.; Frink, Neal T.; Noack, Ralph W.

2005-01-01

A static and dynamic Chimera overset-grid capability is added to an established NASA tetrahedral unstructured parallel Navier-Stokes flow solver, USM3D. Modifications to the solver primarily consist of a few strategic calls to the Donor interpolation Receptor Transaction library (DiRTlib) to facilitate communication of solution information between various grids. The assembly of multiple overlapping grids into a single-zone composite grid is performed by the Structured, Unstructured and Generalized Grid AssembleR (SUGGAR) code. Several test cases are presented to verify the implementation, assess overset-grid solution accuracy and convergence relative to single-grid solutions, and demonstrate the prescribed relative grid motion capability.

36 CFR § 1236.24 - What are the additional requirements for managing unstructured electronic records?

Code of Federal Regulations, 2013 CFR

2013-07-01

... requirements for managing unstructured electronic records? § 1236.24 Section § 1236.24 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION RECORDS MANAGEMENT ELECTRONIC RECORDS MANAGEMENT Additional Requirements for Electronic Records § 1236.24 What are the additional requirements for...

Teaching Social Media Analytics: An Assessment Based on Natural Disaster Postings

ERIC Educational Resources Information Center

Goh, Tiong T.; Sun, Pei-Chen

2015-01-01

Unstructured data in social media is as part of the "big data" spectrum. Unstructured data in Social media can provide useful insights into social phenomena and citizen opinions, both of which are critical to government policy and businesses decisions. Teachers of business intelligence and analytics commonly use quantitative data from…

Numerical aspects and implementation of a two-layer zonal wall model for LES of compressible turbulent flows on unstructured meshes

NASA Astrophysics Data System (ADS)

Park, George Ilhwan; Moin, Parviz

2016-01-01

This paper focuses on numerical and practical aspects associated with a parallel implementation of a two-layer zonal wall model for large-eddy simulation (LES) of compressible wall-bounded turbulent flows on unstructured meshes. A zonal wall model based on the solution of unsteady three-dimensional Reynolds-averaged Navier-Stokes (RANS) equations on a separate near-wall grid is implemented in an unstructured, cell-centered finite-volume LES solver. The main challenge in its implementation is to couple two parallel, unstructured flow solvers for efficient boundary data communication and simultaneous time integrations. A coupling strategy with good load balancing and low processors underutilization is identified. Face mapping and interpolation procedures at the coupling interface are explained in detail. The method of manufactured solution is used for verifying the correct implementation of solver coupling, and parallel performance of the combined wall-modeled LES (WMLES) solver is investigated. The method has successfully been applied to several attached and separated flows, including a transitional flow over a flat plate and a separated flow over an airfoil at an angle of attack.

A solution-adaptive hybrid-grid method for the unsteady analysis of turbomachinery

NASA Technical Reports Server (NTRS)

Mathur, Sanjay R.; Madavan, Nateri K.; Rajagopalan, R. G.

1993-01-01

A solution-adaptive method for the time-accurate analysis of two-dimensional flows in turbomachinery is described. The method employs a hybrid structured-unstructured zonal grid topology in conjunction with appropriate modeling equations and solution techniques in each zone. The viscous flow region in the immediate vicinity of the airfoils is resolved on structured O-type grids while the rest of the domain is discretized using an unstructured mesh of triangular cells. Implicit, third-order accurate, upwind solutions of the Navier-Stokes equations are obtained in the inner regions. In the outer regions, the Euler equations are solved using an explicit upwind scheme that incorporates a second-order reconstruction procedure. An efficient and robust grid adaptation strategy, including both grid refinement and coarsening capabilities, is developed for the unstructured grid regions. Grid adaptation is also employed to facilitate information transfer at the interfaces between unstructured grids in relative motion. Results for grid adaptation to various features pertinent to turbomachinery flows are presented. Good comparisons between the present results and experimental measurements and earlier structured-grid results are obtained.

Investigation of advancing front method for generating unstructured grid

NASA Technical Reports Server (NTRS)

Thomas, A. M.; Tiwari, S. N.

1992-01-01

The advancing front technique is used to generate an unstructured grid about simple aerodynamic geometries. Unstructured grids are generated using VGRID2D and VGRID3D software. Specific problems considered are a NACA 0012 airfoil, a bi-plane consisting of two NACA 0012 airfoil, a four element airfoil in its landing configuration, and an ONERA M6 wing. Inviscid time dependent solutions are computed on these geometries using USM3D and the results are compared with standard test results obtained by other investigators. A grid convergence study is conducted for the NACA 0012 airfoil and compared with a structured grid. A structured grid is generated using GRIDGEN software and inviscid solutions computed using CFL3D flow solver. The results obtained by unstructured grid for NACA 0012 airfoil showed an asymmetric distribution of flow quantities, and a fine distribution of grid was required to remove this asymmetry. On the other hand, the structured grid predicted a very symmetric distribution, but when the total number of points were compared to obtain the same results it was seen that structured grid required more grid points.

Incorporating Unstructured Socializing Into the Study of Secondary Exposure to Community Violence: Etiological and Empirical Implications.

PubMed

Zimmerman, Gregory M; Messner, Steven F; Rees, Carter

2014-07-01

Secondary exposure to community violence, defined as witnessing or hearing violence in the community, has the potential to profoundly impact long-term development, health, happiness, and security. While research has explored pathways to community violence exposure at the individual, family, and neighborhood levels, prior work has largely neglected situational factors conducive to secondary violence exposure. The present study evaluates "unstructured socializing with peers in the absence of authority figures" as a situational process that has implications for secondary exposure to violence. Results indicate that a measure of unstructured socializing was significantly associated with exposure to violence, net of an array of theoretically relevant covariates of violence exposure. Moreover, the relationships between exposure to violence and three of the most well-established correlates of violence exposure in the literature-age, male, and prior violence-were mediated to varying degrees by unstructured socializing. The results suggest a more nuanced approach to the study of secondary violence exposure that expands the focus of attention beyond individual and neighborhood background factors to include situational opportunities presented by patterns of everyday activities. © The Author(s) 2013.

Modeling and simulation of xylitol production in bioreactor by Debaryomyces nepalensis NCYC 3413 using unstructured and artificial neural network models.

PubMed

Pappu, J Sharon Mano; Gummadi, Sathyanarayana N

2016-11-01

This study examines the use of unstructured kinetic model and artificial neural networks as predictive tools for xylitol production by Debaryomyces nepalensis NCYC 3413 in bioreactor. An unstructured kinetic model was proposed in order to assess the influence of pH (4, 5 and 6), temperature (25°C, 30°C and 35°C) and volumetric oxygen transfer coefficient kLa (0.14h(-1), 0.28h(-1) and 0.56h(-1)) on growth and xylitol production. A feed-forward back-propagation artificial neural network (ANN) has been developed to investigate the effect of process condition on xylitol production. ANN configuration of 6-10-3 layers was selected and trained with 339 experimental data points from bioreactor studies. Results showed that simulation and prediction accuracy of ANN was apparently higher when compared to unstructured mechanistic model under varying operational conditions. ANN was found to be an efficient data-driven tool to predict the optimal harvest time in xylitol production. Copyright © 2016 Elsevier Ltd. All rights reserved.

Protein intrinsic disorder in plants.

PubMed

Pazos, Florencio; Pietrosemoli, Natalia; García-Martín, Juan A; Solano, Roberto

2013-09-12

To some extent contradicting the classical paradigm of the relationship between protein 3D structure and function, now it is clear that large portions of the proteomes, especially in higher organisms, lack a fixed structure and still perform very important functions. Proteins completely or partially unstructured in their native (functional) form are involved in key cellular processes underlain by complex networks of protein interactions. The intrinsic conformational flexibility of these disordered proteins allows them to bind multiple partners in transient interactions of high specificity and low affinity. In concordance, in plants this type of proteins has been found in processes requiring these complex and versatile interaction networks. These include transcription factor networks, where disordered proteins act as integrators of different signals or link different transcription factor subnetworks due to their ability to interact (in many cases simultaneously) with different partners. Similarly, they also serve as signal integrators in signaling cascades, such as those related to response to external stimuli. Disordered proteins have also been found in plants in many stress-response processes, acting as protein chaperones or protecting other cellular components and structures. In plants, it is especially important to have complex and versatile networks able to quickly and efficiently respond to changing environmental conditions since these organisms cannot escape and have no other choice than adapting to them. Consequently, protein disorder can play an especially important role in plants, providing them with a fast mechanism to obtain complex, interconnected and versatile molecular networks.

Protein intrinsic disorder in plants

PubMed Central

Pazos, Florencio; Pietrosemoli, Natalia; García-Martín, Juan A.; Solano, Roberto

2013-01-01

To some extent contradicting the classical paradigm of the relationship between protein 3D structure and function, now it is clear that large portions of the proteomes, especially in higher organisms, lack a fixed structure and still perform very important functions. Proteins completely or partially unstructured in their native (functional) form are involved in key cellular processes underlain by complex networks of protein interactions. The intrinsic conformational flexibility of these disordered proteins allows them to bind multiple partners in transient interactions of high specificity and low affinity. In concordance, in plants this type of proteins has been found in processes requiring these complex and versatile interaction networks. These include transcription factor networks, where disordered proteins act as integrators of different signals or link different transcription factor subnetworks due to their ability to interact (in many cases simultaneously) with different partners. Similarly, they also serve as signal integrators in signaling cascades, such as those related to response to external stimuli. Disordered proteins have also been found in plants in many stress-response processes, acting as protein chaperones or protecting other cellular components and structures. In plants, it is especially important to have complex and versatile networks able to quickly and efficiently respond to changing environmental conditions since these organisms cannot escape and have no other choice than adapting to them. Consequently, protein disorder can play an especially important role in plants, providing them with a fast mechanism to obtain complex, interconnected and versatile molecular networks. PMID:24062761

Development of an unstructured solution adaptive method for the quasi-three-dimensional Euler and Navier-Stokes equations

NASA Technical Reports Server (NTRS)

Jiang, Yi-Tsann

1993-01-01

A general solution adaptive scheme-based on a remeshing technique is developed for solving the two-dimensional and quasi-three-dimensional Euler and Favre-averaged Navier-Stokes equations. The numerical scheme is formulated on an unstructured triangular mesh utilizing an edge-based pointer system which defines the edge connectivity of the mesh structure. Jameson's four-stage hybrid Runge-Kutta scheme is used to march the solution in time. The convergence rate is enhanced through the use of local time stepping and implicit residual averaging. As the solution evolves, the mesh is regenerated adaptively using flow field information. Mesh adaptation parameters are evaluated such that an estimated local numerical error is equally distributed over the whole domain. For inviscid flows, the present approach generates a complete unstructured triangular mesh using the advancing front method. For turbulent flows, the approach combines a local highly stretched structured triangular mesh in the boundary layer region with an unstructured mesh in the remaining regions to efficiently resolve the important flow features. One-equation and two-equation turbulence models are incorporated into the present unstructured approach. Results are presented for a wide range of flow problems including two-dimensional multi-element airfoils, two-dimensional cascades, and quasi-three-dimensional cascades. This approach is shown to gain flow resolution in the refined regions while achieving a great reduction in the computational effort and storage requirements since solution points are not wasted in regions where they are not required.

Indoor and Outdoor Context-Specific Contributions to Early Adolescent Moderate to Vigorous Physical Activity as Measured by Combined Diary, Accelerometer, and GPS.

PubMed

Pearce, Matthew; Saunders, David H; Allison, Peter; Turner, Anthony P

2018-01-01

The distribution of adolescent moderate to vigorous physical activity (MVPA) across multiple contexts is unclear. This study examined indoor and outdoor leisure time in terms of being structured or unstructured and explored relationships with total daily MVPA. Between September 2012 and January 2014, 70 participants (aged 11-13 y) from 4 schools in Edinburgh wore an accelerometer and global positioning system receiver over 7 days, reporting structured physical activity using a diary. Time spent and MVPA were summarized according to indoor/outdoor location and whether activity was structured/unstructured. Independent associations between context-specific time spent and total daily MVPA were examined using a multivariate linear regression model. Very little time or MVPA was recorded in structured contexts. Unstructured outdoor leisure time was associated with an increase in total daily MVPA almost twice that of unstructured indoor leisure time [b value (95% confidence interval), 8.45 (1.71 to 14.48) vs 4.38 (0.20 to 8.22) minute increase per hour spent]. The association was stronger for time spent in structured outdoor leisure time [35.81 (20.60 to 52.27)]. Research and interventions should focus on strategies to facilitate time outdoors during unstructured leisure time and maximize MVPA once youth are outdoors. Increasing the proportion of youth engaging in structured activity may be beneficial given that, although time spent was limited, association with MVPA was strongest.

Description of the F-16XL Geometry and Computational Grids Used in CAWAPI

NASA Technical Reports Server (NTRS)

Boelens, O. J.; Badcock, K. J.; Gortz, S.; Morton, S.; Fritz, W.; Karman, S. L., Jr.; Michal, T.; Lamar, J. E.

2009-01-01

The objective of the Cranked-Arrow Wing Aerodynamics Project International (CAWAPI) was to allow a comprehensive validation of Computational Fluid Dynamics methods against the CAWAP flight database. A major part of this work involved the generation of high-quality computational grids. Prior to the grid generation an IGES file containing the air-tight geometry of the F-16XL aircraft was generated by a cooperation of the CAWAPI partners. Based on this geometry description both structured and unstructured grids have been generated. The baseline structured (multi-block) grid (and a family of derived grids) has been generated by the National Aerospace Laboratory NLR. Although the algorithms used by NLR had become available just before CAWAPI and thus only a limited experience with their application to such a complex configuration had been gained, a grid of good quality was generated well within four weeks. This time compared favourably with that required to produce the unstructured grids in CAWAPI. The baseline all-tetrahedral and hybrid unstructured grids has been generated at NASA Langley Research Center and the USAFA, respectively. To provide more geometrical resolution, trimmed unstructured grids have been generated at EADS-MAS, the UTSimCenter, Boeing Phantom Works and KTH/FOI. All grids generated within the framework of CAWAPI will be discussed in the article. Both results obtained on the structured grids and the unstructured grids showed a significant improvement in agreement with flight test data in comparison with those obtained on the structured multi-block grid used during CAWAP.

Hybrid Grid Techniques for Propulsion Applications

NASA Technical Reports Server (NTRS)

Koomullil, Roy P.; Soni, Bharat K.; Thornburg, Hugh J.

1996-01-01

During the past decade, computational simulation of fluid flow for propulsion activities has progressed significantly, and many notable successes have been reported in the literature. However, the generation of a high quality mesh for such problems has often been reported as a pacing item. Hence, much effort has been expended to speed this portion of the simulation process. Several approaches have evolved for grid generation. Two of the most common are structured multi-block, and unstructured based procedures. Structured grids tend to be computationally efficient, and have high aspect ratio cells necessary for efficently resolving viscous layers. Structured multi-block grids may or may not exhibit grid line continuity across the block interface. This relaxation of the continuity constraint at the interface is intended to ease the grid generation process, which is still time consuming. Flow solvers supporting non-contiguous interfaces require specialized interpolation procedures which may not ensure conservation at the interface. Unstructured or generalized indexing data structures offer greater flexibility, but require explicit connectivity information and are not easy to generate for three dimensional configurations. In addition, unstructured mesh based schemes tend to be less efficient and it is difficult to resolve viscous layers. Recently hybrid or generalized element solution and grid generation techniques have been developed with the objective of combining the attractive features of both structured and unstructured techniques. In the present work, recently developed procedures for hybrid grid generation and flow simulation are critically evaluated, and compared to existing structured and unstructured procedures in terms of accuracy and computational requirements.

Development of an unstructured solution adaptive method for the quasi-three-dimensional Euler and Navier-Stokes equations

NASA Technical Reports Server (NTRS)

Jiang, Yi-Tsann; Usab, William J., Jr.

1993-01-01

A general solution adaptive scheme based on a remeshing technique is developed for solving the two-dimensional and quasi-three-dimensional Euler and Favre-averaged Navier-Stokes equations. The numerical scheme is formulated on an unstructured triangular mesh utilizing an edge-based pointer system which defines the edge connectivity of the mesh structure. Jameson's four-stage hybrid Runge-Kutta scheme is used to march the solution in time. The convergence rate is enhanced through the use of local time stepping and implicit residual averaging. As the solution evolves, the mesh is regenerated adaptively using flow field information. Mesh adaptation parameters are evaluated such that an estimated local numerical error is equally distributed over the whole domain. For inviscid flows, the present approach generates a complete unstructured triangular mesh using the advancing front method. For turbulent flows, the approach combines a local highly stretched structured triangular mesh in the boundary layer region with an unstructured mesh in the remaining regions to efficiently resolve the important flow features. One-equation and two-equation turbulence models are incorporated into the present unstructured approach. Results are presented for a wide range of flow problems including two-dimensional multi-element airfoils, two-dimensional cascades, and quasi-three-dimensional cascades. This approach is shown to gain flow resolution in the refined regions while achieving a great reduction in the computational effort and storage requirements since solution points are not wasted in regions where they are not required.

Unsteady flow simulations around complex geometries using stationary or rotating unstructured grids

NASA Astrophysics Data System (ADS)

Sezer-Uzol, Nilay

In this research, the computational analysis of three-dimensional, unsteady, separated, vortical flows around complex geometries is studied by using stationary or moving unstructured grids. Two main engineering problems are investigated. The first problem is the unsteady simulation of a ship airwake, where helicopter operations become even more challenging, by using stationary unstructured grids. The second problem is the unsteady simulation of wind turbine rotor flow fields by using moving unstructured grids which are rotating with the whole three-dimensional rigid rotor geometry. The three dimensional, unsteady, parallel, unstructured, finite volume flow solver, PUMA2, is used for the computational fluid dynamics (CFD) simulations considered in this research. The code is modified to have a moving grid capability to perform three-dimensional, time-dependent rotor simulations. An instantaneous log-law wall model for Large Eddy Simulations is also implemented in PUMA2 to investigate the very large Reynolds number flow fields of rotating blades. To verify the code modifications, several sample test cases are also considered. In addition, interdisciplinary studies, which are aiming to provide new tools and insights to the aerospace and wind energy scientific communities, are done during this research by focusing on the coupling of ship airwake CFD simulations with the helicopter flight dynamics and control analysis, the coupling of wind turbine rotor CFD simulations with the aeroacoustic analysis, and the analysis of these time-dependent and large-scale CFD simulations with the help of a computational monitoring, steering and visualization tool, POSSE.

Rotor Airloads Prediction Using Unstructured Meshes and Loose CFD/CSD Coupling

NASA Technical Reports Server (NTRS)

Biedron, Robert T.; Lee-Rausch, Elizabeth M.

2008-01-01

The FUN3D unsteady Reynolds-averaged Navier-Stokes solver for unstructured grids has been modified to allow prediction of trimmed rotorcraft airloads. The trim of the rotorcraft and the aeroelastic deformation of the rotor blades are accounted for via loose coupling with the CAMRAD II rotorcraft computational structural dynamics code. The set of codes is used to analyze the HART-II Baseline, Minimum Noise and Minimum Vibration test conditions. The loose coupling approach is found to be stable and convergent for the cases considered. Comparison of the resulting airloads and structural deformations with experimentally measured data is presented. The effect of grid resolution and temporal accuracy is examined. Rotorcraft airloads prediction presents a very substantial challenge for Computational Fluid Dynamics (CFD). Not only must the unsteady nature of the flow be accurately modeled, but since most rotorcraft blades are not structurally stiff, an accurate simulation must account for the blade structural dynamics. In addition, trim of the rotorcraft to desired thrust and moment targets depends on both aerodynamic loads and structural deformation, and vice versa. Further, interaction of the fuselage with the rotor flow field can be important, so that relative motion between the blades and the fuselage must be accommodated. Thus a complete simulation requires coupled aerodynamics, structures and trim, with the ability to model geometrically complex configurations. NASA has recently initiated a Subsonic Rotary Wing (SRW) Project under the overall Fundamental Aeronautics Program. Within the context of SRW are efforts aimed at furthering the state of the art of high-fidelity rotorcraft flow simulations, using both structured and unstructured meshes. Structured-mesh solvers have an advantage in computation speed, but even though remarkably complex configurations may be accommodated using the overset grid approach, generation of complex structured-mesh systems can require months to set up. As a result, many rotorcraft simulations using structured-grid CFD neglect the fuselage. On the other hand, unstructured-mesh solvers are easily able to handle complex geometries, but suffer from slower execution speed. However, advances in both computer hardware and CFD algorithms have made previously state-of-the-art computations routine for unstructured-mesh solvers, so that rotorcraft simulations using unstructured grids are now viable. The aim of the present work is to develop a first principles rotorcraft simulation tool based on an unstructured CFD solver.

Unstructured medical image query using big data - An epilepsy case study.

PubMed

Istephan, Sarmad; Siadat, Mohammad-Reza

2016-02-01

Big data technologies are critical to the medical field which requires new frameworks to leverage them. Such frameworks would benefit medical experts to test hypotheses by querying huge volumes of unstructured medical data to provide better patient care. The objective of this work is to implement and examine the feasibility of having such a framework to provide efficient querying of unstructured data in unlimited ways. The feasibility study was conducted specifically in the epilepsy field. The proposed framework evaluates a query in two phases. In phase 1, structured data is used to filter the clinical data warehouse. In phase 2, feature extraction modules are executed on the unstructured data in a distributed manner via Hadoop to complete the query. Three modules have been created, volume comparer, surface to volume conversion and average intensity. The framework allows for user-defined modules to be imported to provide unlimited ways to process the unstructured data hence potentially extending the application of this framework beyond epilepsy field. Two types of criteria were used to validate the feasibility of the proposed framework - the ability/accuracy of fulfilling an advanced medical query and the efficiency that Hadoop provides. For the first criterion, the framework executed an advanced medical query that spanned both structured and unstructured data with accurate results. For the second criterion, different architectures were explored to evaluate the performance of various Hadoop configurations and were compared to a traditional Single Server Architecture (SSA). The surface to volume conversion module performed up to 40 times faster than the SSA (using a 20 node Hadoop cluster) and the average intensity module performed up to 85 times faster than the SSA (using a 40 node Hadoop cluster). Furthermore, the 40 node Hadoop cluster executed the average intensity module on 10,000 models in 3h which was not even practical for the SSA. The current study is limited to epilepsy field and further research and more feature extraction modules are required to show its applicability in other medical domains. The proposed framework advances data-driven medicine by unleashing the content of unstructured medical data in an efficient and unlimited way to be harnessed by medical experts. Copyright © 2015 Elsevier Inc. All rights reserved.

Overview of SCIAMACHY validation: 2002-2004

NASA Astrophysics Data System (ADS)

Piters, A. J. M.; Bramstedt, K.; Lambert, J.-C.; Kirchhoff, B.

2006-01-01

SCIAMACHY, on board Envisat, has been in operation now for almost three years. This UV/visible/NIR spectrometer measures the solar irradiance, the earthshine radiance scattered at nadir and from the limb, and the attenuation of solar radiation by the atmosphere during sunrise and sunset, from 240 to 2380 nm and at moderate spectral resolution. Vertical columns and profiles of a variety of atmospheric constituents are inferred from the SCIAMACHY radiometric measurements by dedicated retrieval algorithms. With the support of ESA and several international partners, a methodical SCIAMACHY validation programme has been developed jointly by Germany, the Netherlands and Belgium (the three instrument providing countries) to face complex requirements in terms of measured species, altitude range, spatial and temporal scales, geophysical states and intended scientific applications. This summary paper describes the approach adopted to address those requirements.

Since provisional releases of limited data sets in summer 2002, operational SCIAMACHY processors established at DLR on behalf of ESA were upgraded regularly and some data products - level-1b spectra, level-2 O3, NO2, BrO and clouds data - have improved significantly. Validation results summarised in this paper and also reported in this special issue conclude that for limited periods and geographical domains they can already be used for atmospheric research. Nevertheless, current processor versions still experience known limitations that hamper scientific usability in other periods and domains. Free from the constraints of operational processing, seven scientific institutes (BIRA-IASB, IFE/IUP-Bremen, IUP-Heidelberg, KNMI, MPI, SAO and SRON) have developed their own retrieval algorithms and generated SCIAMACHY data products, together addressing nearly all targeted constituents. Most of the UV-visible data products - O3, NO2, SO2, H2O total columns; BrO, OClO slant columns; O3, NO2, BrO profiles - already have acceptable, if not excellent, quality. Provisional near-infrared column products - CO, CH4, N2O and CO2 - have already demonstrated their potential for a variety of applications. Cloud and aerosol parameters are retrieved, suffering from calibration with the exception of cloud cover. In any case, scientific users are advised to read carefully validation reports before using the data. It is required and anticipated that SCIAMACHY validation will continue throughout instrument lifetime and beyond and will accompany regular processor upgrades.

Laparoscopic ovarian drilling versus GnRH antagonist combined with cabergoline as a prophylaxis against the re-development of ovarian hyperstimulation syndrome.

PubMed

Seyam, Emaduldin; Hefzy, Enas

2018-07-01

The aim of this work was to investigate the value of laparoscopic ovarian drilling (LOD) compared with GnRH antagonist flexible protocol combined with cabergoline (Cb), as a prophylaxis against the re-development of ovarian hyperstimulation syndrome (OHSS) in women with clomiphene citrate-resistant polycystic ovary disease (CCR-PCOD) who had severe OHSS before in a previous ICSI cycle. It is a prospective controlled study, where 250 CCR-PCOD women (n = 250) with a history of severe OHSS before, had been recruited for the study. LOD had been performed for 120 (n = 120) of the recruited women before ovarian induction, and considered as group A. GnRH antagonist (Cetrotide 0.25 mg) was added when a leading follicle reaches 14-16 mm combined with oral Cb in a dose 0.5 mg a day before hCG, and for 8 d for another 130 (n = 130) women, and considered as group B. Pregnancy was diagnosed with BhCG level ≥25 IU/L, ± 14 d after embryo transfer, followed with transvaginal ultrasound scanning (TVS) 2 weeks later to confirm intra-uterine pregnancy (IUP). Women were followed up weekly for 3 months for the possible development of any signs and symptoms of OHSS. None of the participants in group A developed severe OHSS, and only six women (5%) developed mild to moderate OHSS. The incidence of severe OHSS was significantly higher (n = 3, 15%) in group B compared with group A (p < .001). Another (n = 17, 13.3%) women in group B developed mild to moderate OHSS. The probability of developing severe OHSS was also significantly higher in group B as well (p = .031). Pregnancy rate (PR) was significantly higher in group A more than group B (67% versus 39%, respectively), and all were single intrauterine pregnancies (IUP) and all developed after fresh embryo transfer (ET), compared with frozen embryo transfer (FET) which was performed in 42 cases in group B after postponing ET due to significantly severe OHSS developed. LOD could be considered a good prophylactic measure against OHSS, in addition to improving the total outcome of IVF cycles in women with CCR-PCOS.

Radiative transfer through terrestrial atmosphere and ocean: Software package SCIATRAN

NASA Astrophysics Data System (ADS)

Rozanov, V. V.; Rozanov, A. V.; Kokhanovsky, A. A.; Burrows, J. P.

2014-01-01

SCIATRAN is a comprehensive software package for the modeling of radiative transfer processes in the terrestrial atmosphere and ocean in the spectral range from the ultraviolet to the thermal infrared (0.18 - 40 μm) including multiple scattering processes, polarization, thermal emission and ocean-atmosphere coupling. The software is capable of modeling spectral and angular distributions of the intensity or the Stokes vector of the transmitted, scattered, reflected, and emitted radiation assuming either a plane-parallel or a spherical atmosphere. Simulations are done either in the scalar or in the vector mode (i.e. accounting for the polarization) for observations by space-, air-, ship- and balloon-borne, ground-based, and underwater instruments in various viewing geometries (nadir, off-nadir, limb, occultation, zenith-sky, off-axis). All significant radiative transfer processes are accounted for. These are, e.g. the Rayleigh scattering, scattering by aerosol and cloud particles, absorption by gaseous components, and bidirectional reflection by an underlying surface including Fresnel reflection from a flat or roughened ocean surface. The software package contains several radiative transfer solvers including finite difference and discrete-ordinate techniques, an extensive database, and a specific module for solving inverse problems. In contrast to many other radiative transfer codes, SCIATRAN incorporates an efficient approach to calculate the so-called Jacobians, i.e. derivatives of the intensity with respect to various atmospheric and surface parameters. In this paper we discuss numerical methods used in SCIATRAN to solve the scalar and vector radiative transfer equation, describe databases of atmospheric, oceanic, and surface parameters incorporated in SCIATRAN, and demonstrate how to solve some selected radiative transfer problems using the SCIATRAN package. During the last decades, a lot of studies have been published demonstrating that SCIATRAN is a valuable tool for a wide range of remote sensing applications. Here, we present some selected comparisons of SCIATRAN simulations to published benchmark results, independent radiative transfer models, and various measurements from satellite, ground-based, and ship instruments. Methods for solving inverse problems related to remote sensing of the Earth's atmosphere using the SCIATRAN software are outside the scope of this study and will be discussed in a follow-up paper. The SCIATRAN software package along with a detailed User's Guide is freely available for non-commercial use via the webpage of the Institute of Environmental Physics (IUP), University of Bremen: http://www.iup.physik.uni-bremen.de/sciatran.

Tandem duplications of a degenerated GTP-binding domain at the origin of GTPase receptors Toc159 and thylakoidal SRP

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

Hernandez Torres, Jorge; Maldonado, Monica Alexandra Arias; Chomilier, Jacques

2007-12-14

The evolutionary origin of some nuclear encoded proteins that translocate proteins across the chloroplast envelope remains unknown. Therefore, sequences of GTPase proteins constituting the Arabidopsis thaliana translocon at the outer membrane of chloroplast (atToc) complexes were analyzed by means of HCA. In particular, atToc159 and related proteins (atToc132, atToc120, and atToc90) do not have proven homologues of prokaryotic or eukaryotic ancestry. We established that the three domains commonly referred to as A, G, and M originate from the GTPase G domain, tandemly repeated, and probably evolving toward an unstructured conformation in the case of the A domain. It resulted frommore » this study a putative common ancestor for these proteins and a new domain definition, in particular the splitting of A into three domains (A1, A2, and A3), has been proposed. The family of Toc159, previously containing A. thaliana and Pisum sativum, has been extended to Medicago truncatula and Populus trichocarpa and it has been revised for Oryza sativa. They have also been compared to GTPase subunits involved in the cpSRP system. A distant homology has been revealed among Toc and cpSRP GTP-hydrolyzing proteins of A. thaliana, and repetitions of a GTPase domain were also found in cpSRP protein receptors, by means of HCA analysis.« less

Unstructured Adaptive (UA) NAS Parallel Benchmark. Version 1.0

NASA Technical Reports Server (NTRS)

Feng, Huiyu; VanderWijngaart, Rob; Biswas, Rupak; Mavriplis, Catherine

2004-01-01

We present a complete specification of a new benchmark for measuring the performance of modern computer systems when solving scientific problems featuring irregular, dynamic memory accesses. It complements the existing NAS Parallel Benchmark suite. The benchmark involves the solution of a stylized heat transfer problem in a cubic domain, discretized on an adaptively refined, unstructured mesh.

Young Children's Opportunities for Unstructured Environmental Exploration of Nature: Links to Adults' Experiences in Childhood

ERIC Educational Resources Information Center

Laird, Shelby Gull; McFarland-Piazza, Laura; Allen, Sydnye

2014-01-01

Outdoor environmental education and provision of unstructured exploration of nature are often forgotten aspects of the early childhood experience. The aim of this study was to understand how adults' early experiences in nature relate to their attitudes and practices in providing such experiences for young children. This study surveyed 33 parents…

2D Mesh Manipulation

DTIC Science & Technology

2011-11-01

the Poisson form of the equations can also be generated by manipulating the computational space , so forcing functions become superfluous . The...ABSTRACT Unstructured methods for region discretization have become common in computational fluid dynamics (CFD) analysis because of certain benefits...application of Winslow elliptic smoothing equations to unstructured meshes. It has been shown that it is not necessary for the computational space of

Learning to Take an Inquiry Stance in Teacher Research: An Exploration of Unstructured Thought-Partner Spaces

ERIC Educational Resources Information Center

Lawton-Sticklor, Nastasia; Bodamer, Scott F.

2016-01-01

This article explores a research partnership between a university-based researcher and a middle school science teacher. Our partnership began with project-based inquiry and continued with unstructured thought-partner spaces: meetings with no agenda where we wrestled with problems of practice. Framed as incubation periods, these meetings allowed us…

Implementation of a parallel unstructured Euler solver on shared and distributed memory architectures

NASA Technical Reports Server (NTRS)

Mavriplis, D. J.; Das, Raja; Saltz, Joel; Vermeland, R. E.

1992-01-01

An efficient three dimensional unstructured Euler solver is parallelized on a Cray Y-MP C90 shared memory computer and on an Intel Touchstone Delta distributed memory computer. This paper relates the experiences gained and describes the software tools and hardware used in this study. Performance comparisons between two differing architectures are made.

Development of a solution adaptive unstructured scheme for quasi-3D inviscid flows through advanced turbomachinery cascades

NASA Technical Reports Server (NTRS)

Usab, William J., Jr.; Jiang, Yi-Tsann

1991-01-01

The objective of the present research is to develop a general solution adaptive scheme for the accurate prediction of inviscid quasi-three-dimensional flow in advanced compressor and turbine designs. The adaptive solution scheme combines an explicit finite-volume time-marching scheme for unstructured triangular meshes and an advancing front triangular mesh scheme with a remeshing procedure for adapting the mesh as the solution evolves. The unstructured flow solver has been tested on a series of two-dimensional airfoil configurations including a three-element analytic test case presented here. Mesh adapted quasi-three-dimensional Euler solutions are presented for three spanwise stations of the NASA rotor 67 transonic fan. Computed solutions are compared with available experimental data.

NCAR global model topography generation software for unstructured grids

NASA Astrophysics Data System (ADS)

Lauritzen, P. H.; Bacmeister, J. T.; Callaghan, P. F.; Taylor, M. A.

2015-06-01

It is the purpose of this paper to document the NCAR global model topography generation software for unstructured grids. Given a model grid, the software computes the fraction of the grid box covered by land, the gridbox mean elevation, and associated sub-grid scale variances commonly used for gravity wave and turbulent mountain stress parameterizations. The software supports regular latitude-longitude grids as well as unstructured grids; e.g. icosahedral, Voronoi, cubed-sphere and variable resolution grids. As an example application and in the spirit of documenting model development, exploratory simulations illustrating the impacts of topographic smoothing with the NCAR-DOE CESM (Community Earth System Model) CAM5.2-SE (Community Atmosphere Model version 5.2 - Spectral Elements dynamical core) are shown.

RIACS

NASA Technical Reports Server (NTRS)

Oliger, Joseph

1997-01-01

Topics considered include: high-performance computing; cognitive and perceptual prostheses (computational aids designed to leverage human abilities); autonomous systems. Also included: development of a 3D unstructured grid code based on a finite volume formulation and applied to the Navier-stokes equations; Cartesian grid methods for complex geometry; multigrid methods for solving elliptic problems on unstructured grids; algebraic non-overlapping domain decomposition methods for compressible fluid flow problems on unstructured meshes; numerical methods for the compressible navier-stokes equations with application to aerodynamic flows; research in aerodynamic shape optimization; S-HARP: a parallel dynamic spectral partitioner; numerical schemes for the Hamilton-Jacobi and level set equations on triangulated domains; application of high-order shock capturing schemes to direct simulation of turbulence; multicast technology; network testbeds; supercomputer consolidation project.

Laminar and turbulent flow computations of Type 4 shock-shock interference aerothermal loads using unstructured grids

NASA Technical Reports Server (NTRS)

Vemaganti, Gururaja R.

1994-01-01

This report presents computations for the Type 4 shock-shock interference flow under laminar and turbulent conditions using unstructured grids. Mesh adaptation was accomplished by remeshing, refinement, and mesh movement. Two two-equation turbulence models were used to analyze turbulent flows. The mean flow governing equations and the turbulence governing equations are solved in a coupled manner. The solution algorithm and the details pertaining to its implementation on unstructured grids are described. Computations were performed at two different freestream Reynolds numbers at a freestream Mach number of 11. Effects of the variation in the impinging shock location are studied. The comparison of the results in terms of wall heat flux and wall pressure distributions is presented.

A note on implementation of decaying product correlation structures for quasi-least squares.

PubMed

Shults, Justine; Guerra, Matthew W

2014-08-30

This note implements an unstructured decaying product matrix via the quasi-least squares approach for estimation of the correlation parameters in the framework of generalized estimating equations. The structure we consider is fairly general without requiring the large number of parameters that are involved in a fully unstructured matrix. It is straightforward to show that the quasi-least squares estimators of the correlation parameters yield feasible values for the unstructured decaying product structure. Furthermore, subject to conditions that are easily checked, the quasi-least squares estimators are valid for longitudinal Bernoulli data. We demonstrate implementation of the structure in a longitudinal clinical trial with both a continuous and binary outcome variable. Copyright © 2014 John Wiley & Sons, Ltd.

Extended bounds limiter for high-order finite-volume schemes on unstructured meshes

NASA Astrophysics Data System (ADS)

Tsoutsanis, Panagiotis

2018-06-01

This paper explores the impact of the definition of the bounds of the limiter proposed by Michalak and Ollivier-Gooch in [56] (2009), for higher-order Monotone-Upstream Central Scheme for Conservation Laws (MUSCL) numerical schemes on unstructured meshes in the finite-volume (FV) framework. A new modification of the limiter is proposed where the bounds are redefined by utilising all the spatial information provided by all the elements in the reconstruction stencil. Numerical results obtained on smooth and discontinuous test problems of the Euler equations on unstructured meshes, highlight that the newly proposed extended bounds limiter exhibits superior performance in terms of accuracy and mesh sensitivity compared to the cell-based or vertex-based bounds implementations.

Context Oriented Information Integration

NASA Astrophysics Data System (ADS)

Mohania, Mukesh; Bhide, Manish; Roy, Prasan; Chakaravarthy, Venkatesan T.; Gupta, Himanshu

Faced with growing knowledge management needs, enterprises are increasingly realizing the importance of seamlessly integrating critical business information distributed across both structured and unstructured data sources. Academicians have focused on this problem but there still remain a lot of obstacles for its widespread use in practice. One of the key problems is the absence of schema in unstructured text. In this paper we present a new paradigm for integrating information which overcomes this problem - that of Context Oriented Information Integration. The goal is to integrate unstructured data with the structured data present in the enterprise and use the extracted information to generate actionable insights for the enterprise. We present two techniques which enable context oriented information integration and show how they can be used for solving real world problems.

Red fluorescent protein responsible for pigmentation in trematode-infected Porites compressa tissues.

PubMed

Palmer, Caroline V; Roth, Melissa S; Gates, Ruth D

2009-02-01

Reports of coral disease have increased dramatically over the last decade; however, the biological mechanisms that corals utilize to limit infection and resist disease remain poorly understood. Compromised coral tissues often display non-normal pigmentation that potentially represents an inflammation-like response, although these pigments remain uncharacterized. Using spectral emission analysis and cryo-histological and electrophoretic techniques, we investigated the pink pigmentation associated with trematodiasis, infection with Podocotyloides stenometre larval trematode, in Porites compressa. Spectral emission analysis reveals that macroscopic areas of pink pigmentation fluoresce under blue light excitation (450 nm) and produce a broad emission peak at 590 nm (+/-6) with a 60-nm full width at half maximum. Electrophoretic protein separation of pigmented tissue extract confirms the red fluorescence to be a protein rather than a low-molecular-weight compound. Histological sections demonstrate green fluorescence in healthy coral tissue and red fluorescence in the trematodiasis-compromised tissue. The red fluorescent protein (FP) is limited to the epidermis, is not associated with cells or granules, and appears unstructured. These data collectively suggest that the red FP is produced and localized in tissue infected by larval trematodes and plays a role in the immune response in corals.

Measles Virus Hemagglutinin Protein Epitopes: The Basis of Antigenic Stability.

PubMed

Tahara, Maino; Bürckert, Jean-Philippe; Kanou, Kazuhiko; Maenaka, Katsumi; Muller, Claude P; Takeda, Makoto

2016-08-02

Globally eliminating measles using available vaccines is biologically feasible because the measles virus (MV) hemagglutinin (H) protein is antigenically stable. The H protein is responsible for receptor binding, and is the main target of neutralizing antibodies. The immunodominant epitope, known as the hemagglutinating and noose epitope, is located near the receptor-binding site (RBS). The RBS also contains an immunodominant epitope. Loss of receptor binding correlates with an escape from the neutralization by antibodies that target the epitope at RBS. Another neutralizing epitope is located near RBS and is shielded by an N-linked sugar in certain genotype strains. However, human sera from vaccinees and measles patients neutralized all MV strains with similar efficiencies, regardless of the N-linked sugar modification or mutations at these epitopes. Two other major epitopes exist at a distance from RBS. One has an unstructured flexible domain with a linear neutralizing epitope. When MV-H forms a tetramer (dimer of dimers), these epitopes may form the dimer-dimer interface, and one of the two epitopes may also interact with the F protein. The neutralization mechanisms of antibodies that recognize these epitopes may involve inhibiting the H-F interaction or blocking the fusion cascade after MV-H binds to its receptors.

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

Shi, Jade; Nobrega, R. Paul; Schwantes, Christian

The dynamics of globular proteins can be described in terms of transitions between a folded native state and less-populated intermediates, or excited states, which can play critical roles in both protein folding and function. Excited states are by definition transient species, and therefore are difficult to characterize using current experimental techniques. We report an atomistic model of the excited state ensemble of a stabilized mutant of an extensively studied flavodoxin fold protein CheY. We employed a hybrid simulation and experimental approach in which an aggregate 42 milliseconds of all-atom molecular dynamics were used as an informative prior for the structuremore » of the excited state ensemble. The resulting prior was then refined against small-angle X-ray scattering (SAXS) data employing an established method (EROS). The most striking feature of the resulting excited state ensemble was an unstructured N-terminus stabilized by non-native contacts in a conformation that is topologically simpler than the native state. We then predict incisive single molecule FRET experiments, using these results, as a means of model validation. Our study demonstrates the paradigm of uniting simulation and experiment in a statistical model to study the structure of protein excited states and rationally design validating experiments.« less

Edge strand engineering prevents native-like aggregation in Sulfolobus solfataricus acylphosphatase.

PubMed

de Rosa, Matteo; Bemporad, Francesco; Pellegrino, Sara; Chiti, Fabrizio; Bolognesi, Martino; Ricagno, Stefano

2014-09-01

β-proteins are constantly threatened by the risk of aggregation because β-sheets are inherently structured for edge-to-edge interactions. To avoid native-like aggregation, evolution has resulted in a set of strategies that prevent intermolecular β-interactions. Acylphosphatase from Sulfolobus solfataricus (Sso AcP) represents a suitable model for the study of such a process. Under conditions promoting aggregation, Sso AcP acquires a native-like conformational state whereby an unstructured N-terminal segment interacts with the edge β-strand B4 of an adjacent Sso AcP molecule. Because B4 is poorly protected against aggregation, this interaction triggers the aggregation cascade without the need for unfolding. Recently, three single Sso AcP mutants (V84D, Y86E and V84P) were designed to engineer additional protection against aggregation in B4 and were observed to successfully impair native-like aggregation in all three variants at the expense of a lower stability. To understand the structural basis of the reduced aggregation propensity and lower stability, the crystal structures of the Sso AcP variants were determined in the present study. Structural analysis reveals that the V84D and Y86E mutations exert protection by the insertion of an edge negative charge. A conformationally less regular B4 underlies protection against aggregation in the V84P mutant. The thermodynamic basis of instability is discussed. Moreover, kinetic experiments indicate that aggregation of the three mutants is not native-like and is independent of the interaction between B4 and the unstructured N-terminal segment. The reported data rationalize previous evidence regarding Sso AcP native-like aggregation and provide a basis for the design of aggregation-free proteins. The atomic coordinates and related experimental data for the Sso AcP mutants V84P, V84D, ΔN11 Y86E have been deposited in the Protein Data Bank under accession numbers 4OJ3, 4OJG and 4OJH, respectively. • Sso AcP and Sso AcP bind by fluorescence technology (View interaction). © 2014 FEBS.

Intrinsic disorder in Viral Proteins Genome-Linked: experimental and predictive analyses

PubMed Central

Hébrard, Eugénie; Bessin, Yannick; Michon, Thierry; Longhi, Sonia; Uversky, Vladimir N; Delalande, François; Van Dorsselaer, Alain; Romero, Pedro; Walter, Jocelyne; Declerk, Nathalie; Fargette, Denis

2009-01-01

Background VPgs are viral proteins linked to the 5' end of some viral genomes. Interactions between several VPgs and eukaryotic translation initiation factors eIF4Es are critical for plant infection. However, VPgs are not restricted to phytoviruses, being also involved in genome replication and protein translation of several animal viruses. To date, structural data are still limited to small picornaviral VPgs. Recently three phytoviral VPgs were shown to be natively unfolded proteins. Results In this paper, we report the bacterial expression, purification and biochemical characterization of two phytoviral VPgs, namely the VPgs of Rice yellow mottle virus (RYMV, genus Sobemovirus) and Lettuce mosaic virus (LMV, genus Potyvirus). Using far-UV circular dichroism and size exclusion chromatography, we show that RYMV and LMV VPgs are predominantly or partly unstructured in solution, respectively. Using several disorder predictors, we show that both proteins are predicted to possess disordered regions. We next extend theses results to 14 VPgs representative of the viral diversity. Disordered regions were predicted in all VPg sequences whatever the genus and the family. Conclusion Based on these results, we propose that intrinsic disorder is a common feature of VPgs. The functional role of intrinsic disorder is discussed in light of the biological roles of VPgs. PMID:19220875

Charged groups at binding interfaces of the PsbO subunit of photosystem II: A combined bioinformatics and simulation study.

PubMed

Del Val, Coral; Bondar, Ana-Nicoleta

2017-06-01

PsbO is an extrinsic subunit of photosystem II engaged in complex binding interactions within photosystem II. At the interface between PsbO, D1 and D2 subunits of photosystem II, a cluster of charged and polar groups of PsbO is part of an extended hydrogen-bond network thought to participate in proton transfer. The precise role of specific amino acid residues at this complex binding interface remains a key open question. Here, we address this question by carrying out extensive bioinformatics analyses and molecular dynamics simulations of PsbO proteins with mutations at the binding interface. We find that PsbO proteins from cyanobacteria vs. plants have specific preferences for the number and composition of charged amino acid residues that may ensure that PsbO proteins avoid aggregation and expose long unstructured loops for binding to photosystem II. A cluster of conserved charged groups with dynamic hydrogen bonds provides PsbO with structural plasticity at the binding interface with photosystem II. Copyright © 2017. Published by Elsevier B.V.

Preprotein mature domains contain translocase targeting signals that are essential for secretion.

PubMed

Chatzi, Katerina E; Sardis, Marios Frantzeskos; Tsirigotaki, Alexandra; Koukaki, Marina; Šoštarić, Nikolina; Konijnenberg, Albert; Sobott, Frank; Kalodimos, Charalampos G; Karamanou, Spyridoula; Economou, Anastassios

2017-05-01

Secretory proteins are only temporary cytoplasmic residents. They are typically synthesized as pre proteins, carrying signal peptides N-terminally fused to their mature domains. In bacteria secretion largely occurs posttranslationally through the membrane-embedded SecA-SecYEG translocase. Upon crossing the plasma membrane, signal peptides are cleaved off and mature domains reach their destinations and fold. Targeting to the translocase is mediated by signal peptides. The role of mature domains in targeting and secretion is unclear. We now reveal that mature domains harbor their own independent targeting signals (mature domain targeting signals [MTSs]). These are multiple, degenerate, interchangeable, linear or 3D hydrophobic stretches that become available because of the unstructured states of targeting-competent preproteins. Their receptor site on the cytoplasmic face of the SecYEG-bound SecA is also of hydrophobic nature and is located adjacent to the signal peptide cleft. Both the preprotein MTSs and their receptor site on SecA are essential for protein secretion. Evidently, mature domains have their own previously unsuspected distinct roles in preprotein targeting and secretion. © 2017 Chatzi et al.

Identification of a Degradation Signal Sequence within Substrates of the Mitochondrial i-AAA Protease.

PubMed

Rampello, Anthony J; Glynn, Steven E

2017-03-24

The i-AAA protease is a component of the mitochondrial quality control machinery that regulates respiration, mitochondrial dynamics, and protein import. The protease is required to select specific substrates for degradation from among the diverse complement of proteins present in mitochondria, yet the rules that govern this selection are unclear. Here, we reconstruct the yeast i-AAA protease, Yme1p, to examine the in vitro degradation of two intermembrane space chaperone subunits, Tim9 and Tim10. Yme1p degrades Tim10 more rapidly than Tim9 despite high sequence and structural similarity, and loss of Tim10 is accelerated by the disruption of conserved disulfide bonds within the substrate. An unstructured N-terminal region of Tim10 is necessary and sufficient to target the substrate to the protease through recognition of a short phenylalanine-rich motif, and the presence of similar motifs in other small Tim proteins predicts robust degradation by the protease. Together, these results identify the first specific degron sequence within a native i-AAA protease substrate. Copyright © 2017 Elsevier Ltd. All rights reserved.

The solution structures of the cucumber mosaic virus and tomato aspermy virus coat proteins explored with molecular dynamics simulations.

PubMed

Gellért, Akos; Balázs, Ervin

2010-02-26

The three-dimensional structures of two cucumovirus coat proteins (CP), namely Cucumber mosaic virus (CMV) and Tomato aspermy virus (TAV), were explored by molecular dynamics (MD) simulations. The N-terminal domain and the C-terminal tail of the CPs proved to be intrinsically unstructured protein regions in aqueous solution. The N-terminal alpha-helix had a partially unrolled conformation. The thermal factor analysis of the CP loop regions demonstrated that the CMV CP had more flexible loop regions than the TAV CP. The principal component analysis (PCA) of the MD trajectories showed that the first three eigenvectors represented the three main conformational motions in the CPs. The first motion components with the highest variance contribution described an opening movement between the hinge and the N-terminal domain of both CPs. The second eigenvector showed a closing motion, while the third eigenvector represented crosswise conformational fluctuations. These new findings, together with previous results, suggest that the hinge region of CPs plays a central role in the recognition and binding of viral RNA. Copyright 2009 Elsevier Inc. All rights reserved.

Assessment of Hybrid RANS/LES Turbulence Models for Aeroacoustics Applications

NASA Technical Reports Server (NTRS)

Vatsa, Veer N.; Lockard, David P.

2010-01-01

Predicting the noise from aircraft with exposed landing gear remains a challenging problem for the aeroacoustics community. Although computational fluid dynamics (CFD) has shown promise as a technique that could produce high-fidelity flow solutions, generating grids that can resolve the pertinent physics around complex configurations can be very challenging. Structured grids are often impractical for such configurations. Unstructured grids offer a path forward for simulating complex configurations. However, few unstructured grid codes have been thoroughly tested for unsteady flow problems in the manner needed for aeroacoustic prediction. A widely used unstructured grid code, FUN3D, is examined for resolving the near field in unsteady flow problems. Although the ultimate goal is to compute the flow around complex geometries such as the landing gear, simpler problems that include some of the relevant physics, and are easily amenable to the structured grid approaches are used for testing the unstructured grid approach. The test cases chosen for this study correspond to the experimental work on single and tandem cylinders conducted in the Basic Aerodynamic Research Tunnel (BART) and the Quiet Flow Facility (QFF) at NASA Langley Research Center. These configurations offer an excellent opportunity to assess the performance of hybrid RANS/LES turbulence models that transition from RANS in unresolved regions near solid bodies to LES in the outer flow field. Several of these models have been implemented and tested in both structured and unstructured grid codes to evaluate their dependence on the solver and mesh type. Comparison of FUN3D solutions with experimental data and numerical solutions from a structured grid flow solver are found to be encouraging.

Integrating Structured and Unstructured EHR Data Using an FHIR-based Type System: A Case Study with Medication Data.

PubMed

Hong, Na; Wen, Andrew; Shen, Feichen; Sohn, Sunghwan; Liu, Sijia; Liu, Hongfang; Jiang, Guoqian

2018-01-01

Standards-based modeling of electronic health records (EHR) data holds great significance for data interoperability and large-scale usage. Integration of unstructured data into a standard data model, however, poses unique challenges partially due to heterogeneous type systems used in existing clinical NLP systems. We introduce a scalable and standards-based framework for integrating structured and unstructured EHR data leveraging the HL7 Fast Healthcare Interoperability Resources (FHIR) specification. We implemented a clinical NLP pipeline enhanced with an FHIR-based type system and performed a case study using medication data from Mayo Clinic's EHR. Two UIMA-based NLP tools known as MedXN and MedTime were integrated in the pipeline to extract FHIR MedicationStatement resources and related attributes from unstructured medication lists. We developed a rule-based approach for assigning the NLP output types to the FHIR elements represented in the type system, whereas we investigated the FHIR elements belonging to the source of the structured EMR data. We used the FHIR resource "MedicationStatement" as an example to illustrate our integration framework and methods. For evaluation, we manually annotated FHIR elements in 166 medication statements from 14 clinical notes generated by Mayo Clinic in the course of patient care, and used standard performance measures (precision, recall and f-measure). The F-scores achieved ranged from 0.73 to 0.99 for the various FHIR element representations. The results demonstrated that our framework based on the FHIR type system is feasible for normalizing and integrating both structured and unstructured EHR data.

Effects of domain-specific exercise load on speed and accuracy of a domain-specific perceptual-cognitive task.

PubMed

Schapschröer, M; Baker, J; Schorer, J

2016-08-01

In the context of perceptual-cognitive expertise it is important to know whether physiological loads influence perceptual-cognitive performance. This study examined whether a handball specific physical exercise load influenced participants' speed and accuracy in a flicker task. At rest and during a specific interval exercise of 86.5-90% HRmax, 35 participants (experts: n=8, advanced: n=13, novices, n=14) performed a handball specific flicker task with two types of patterns (structured and unstructured). For reaction time, results revealed moderate effect sizes for group, with experts reacting faster than advanced and advanced reacting faster than novices, and for structure, with structured videos being performed faster than unstructured ones. A significant interaction for structure×group was also found, with experts and advanced players faster for structured videos, and novices faster for unstructured videos. For accuracy, significant main effects were found for structure with structured videos solved more accurately. A significant interaction for structure×group was revealed, with experts and advanced more accurate for structured scenes and novices more accurate for unstructured scenes. A significant interaction was also found for condition×structure; at rest, unstructured and structured scenes were performed with the same accuracy while under physical exercise, structured scenes were solved more accurately. No other interactions were found. These results were somewhat surprising given previous work in this area, although the impact of a specific physical exercise on a specific perceptual-cognitive task may be different from those tested generally. Copyright © 2016 Elsevier B.V. All rights reserved.

Computer Science Students' Attitudes towards the Use of Structured and Unstructured Discussion Forums in Fully Online Courses

ERIC Educational Resources Information Center

Tibi, Moanes H.

2018-01-01

This study aims to investigate and analyze the attitudes and opinions of computer science students at two academic colleges of education with regards to the use of structured and unstructured discussion forums in computer science courses conducted entirely online. Fifty-two students participated in two online courses. The students in each course…

A mesh regeneration method using quadrilateral and triangular elements for compressible flows

NASA Technical Reports Server (NTRS)

Vemaganti, G. R.; Thornton, E. A.

1989-01-01

An adaptive remeshing method using both triangular and quadrilateral elements suitable for high-speed viscous flows is presented. For inviscid flows, the method generates completely unstructured meshes. For viscous flows, structured meshes are generated for boundary layers, and unstructured meshes are generated for inviscid flow regions. Examples of inviscid and viscous adaptations for high-speed flows are presented.

Center for Efficient Exascale Discretizations Software Suite

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

Kolev, Tzanio; Dobrev, Veselin; Tomov, Vladimir

The CEED Software suite is a collection of generally applicable software tools focusing on the following computational motives: PDE discretizations on unstructured meshes, high-order finite element and spectral element methods and unstructured adaptive mesh refinement. All of this software is being developed as part of CEED, a co-design Center for Efficient Exascale Discretizations, within DOE's Exascale Computing Project (ECP) program.

Hanging out with Which Friends? Friendship-Level Predictors of Unstructured and Unsupervised Socializing in Adolescence

ERIC Educational Resources Information Center

Siennick, Sonja E.; Osgood, D. Wayne

2012-01-01

Companions are central to explanations of the risky nature of unstructured and unsupervised socializing, yet we know little about whom adolescents are with when hanging out. We examine predictors of how often friendship dyads hang out via multilevel analyses of longitudinal friendship-level data on over 5,000 middle schoolers. Adolescents hang out…

Impact of Machine-Translated Text on Entity and Relationship Extraction

DTIC Science & Technology

2014-12-01

20 1 1. Introduction Using social network analysis tools is an important asset in...semantic modeling software to automatically build detailed network models from unstructured text. Contour imports unstructured text and then maps the text...onto an existing ontology of frames at the sentence level, using FrameNet, a structured language model, and through Semantic Role Labeling ( SRL

On unstructured grids and solvers

NASA Technical Reports Server (NTRS)

Barth, T. J.

1990-01-01

The fundamentals and the state-of-the-art technology for unstructured grids and solvers are highlighted. Algorithms and techniques pertinent to mesh generation are discussed. It is shown that grid generation and grid manipulation schemes rely on fast multidimensional searching. Flow solution techniques for the Euler equations, which can be derived from the integral form of the equations are discussed. Sample calculations are also provided.

Consequences of the Allee effect and intraspecific competition on population persistence under adverse environmental conditions.

PubMed

Petrovskii, Sergei; Blackshaw, Rod; Li, Bai-Lian

2008-02-01

The impact of intraspecific interactions on ecological stability and population persistence in terms of steady state(s) existence is considered theoretically based on a general competition model. We compare persistence of a structured population consisting of a few interacting (competitive) subpopulations, or groups, to persistence of the corresponding unstructured population. For a general case, we show that if the intra-group competition is stronger than the inter-group competition, then the structured population is less prone to extinction, i.e. it can persist in a parameter range where the unstructured population goes extinct. For a more specific case of a population with hierarchical competition, we show that relative viability of structured and unstructured populations depend on the type of density dependence in the population growth. Namely, while in the case of logistic growth, structured and unstructured populations exhibit equivalent persistence; in the case of Allee dynamics, the persistence of a hierarchically structured population is shown to be higher. We then apply these results to the case of behaviourally structured populations and demonstrate that an extreme form of individual aggression can be beneficial at the population level and enhance population persistence.

Finding geospatial pattern of unstructured data by clustering routes

NASA Astrophysics Data System (ADS)

Boustani, M.; Mattmann, C. A.; Ramirez, P.; Burke, W.

2016-12-01

Today the majority of data generated has a geospatial context to it. Either in attribute form as a latitude or longitude, or name of location or cross referenceable using other means such as an external gazetteer or location service. Our research is interested in exploiting geospatial location and context in unstructured data such as that found on the web in HTML pages, images, videos, documents, and other areas, and in structured information repositories found on intranets, in scientific environments, and otherwise. We are working together on the DARPA MEMEX project to exploit open source software tools such as the Lucene Geo Gazetteer, Apache Tika, Apache Lucene, and Apache OpenNLP, to automatically extract, and make meaning out of geospatial information. In particular, we are interested in unstructured descriptors e.g., a phone number, or a named entity, and the ability to automatically learn geospatial paths related to these descriptors. For example, a particular phone number may represent an entity that travels on a monthly basis, according to easily identifiable and somes more difficult to track patterns. We will present a set of automatic techniques to extract descriptors, and then to geospatially infer their paths across unstructured data.

Unstructured Socializing with Peers and Delinquent Behavior: A Genetically Informed Analysis.

PubMed

Meldrum, Ryan C; Barnes, J C

2017-09-01

A large body of research finds that unstructured socializing with peers is positively associated with delinquency during adolescence. Yet, existing research has not ruled out the potential for confounding due to genetic factors and factors that can be traced to environments shared between siblings. To fill this void, the current study examines whether the association between unstructured socializing with peers and delinquent behavior remains when accounting for genetic factors, shared environmental influences, and a variety of non-shared environmental covariates. We do so by using data from the twin subsample of the National Longitudinal Study of Adolescent to Adult Health (n = 1200 at wave 1 and 1103 at wave 2; 51% male; mean age at wave 1 = 15.63). Results from both cross-sectional and lagged models indicate the association between unstructured socializing with peers and delinquent behavior remains when controlling for both genetic and environmental influences. Supplementary analyses examining the association under different specifications offer additional, albeit qualified, evidence supportive of this finding. The study concludes with a discussion highlighting the importance of limiting free time with friends in the absence of authority figures as a strategy for reducing delinquency during adolescence.

Collaborative human-machine analysis to disambiguate entities in unstructured text and structured datasets

NASA Astrophysics Data System (ADS)

Davenport, Jack H.

2016-05-01

Intelligence analysts demand rapid information fusion capabilities to develop and maintain accurate situational awareness and understanding of dynamic enemy threats in asymmetric military operations. The ability to extract relationships between people, groups, and locations from a variety of text datasets is critical to proactive decision making. The derived network of entities must be automatically created and presented to analysts to assist in decision making. DECISIVE ANALYTICS Corporation (DAC) provides capabilities to automatically extract entities, relationships between entities, semantic concepts about entities, and network models of entities from text and multi-source datasets. DAC's Natural Language Processing (NLP) Entity Analytics model entities as complex systems of attributes and interrelationships which are extracted from unstructured text via NLP algorithms. The extracted entities are automatically disambiguated via machine learning algorithms, and resolution recommendations are presented to the analyst for validation; the analyst's expertise is leveraged in this hybrid human/computer collaborative model. Military capability is enhanced by these NLP Entity Analytics because analysts can now create/update an entity profile with intelligence automatically extracted from unstructured text, thereby fusing entity knowledge from structured and unstructured data sources. Operational and sustainment costs are reduced since analysts do not have to manually tag and resolve entities.

An Introduction to Natural Language Processing: How You Can Get More From Those Electronic Notes You Are Generating.

PubMed

Kimia, Amir A; Savova, Guergana; Landschaft, Assaf; Harper, Marvin B

2015-07-01

Electronically stored clinical documents may contain both structured data and unstructured data. The use of structured clinical data varies by facility, but clinicians are familiar with coded data such as International Classification of Diseases, Ninth Revision, Systematized Nomenclature of Medicine-Clinical Terms codes, and commonly other data including patient chief complaints or laboratory results. Most electronic health records have much more clinical information stored as unstructured data, for example, clinical narrative such as history of present illness, procedure notes, and clinical decision making are stored as unstructured data. Despite the importance of this information, electronic capture or retrieval of unstructured clinical data has been challenging. The field of natural language processing (NLP) is undergoing rapid development, and existing tools can be successfully used for quality improvement, research, healthcare coding, and even billing compliance. In this brief review, we provide examples of successful uses of NLP using emergency medicine physician visit notes for various projects and the challenges of retrieving specific data and finally present practical methods that can run on a standard personal computer as well as high-end state-of-the-art funded processes run by leading NLP informatics researchers.

Queries over Unstructured Data: Probabilistic Methods to the Rescue

NASA Astrophysics Data System (ADS)

Sarawagi, Sunita

Unstructured data like emails, addresses, invoices, call transcripts, reviews, and press releases are now an integral part of any large enterprise. A challenge of modern business intelligence applications is analyzing and querying data seamlessly across structured and unstructured sources. This requires the development of automated techniques for extracting structured records from text sources and resolving entity mentions in data from various sources. The success of any automated method for extraction and integration depends on how effectively it unifies diverse clues in the unstructured source and in existing structured databases. We argue that statistical learning techniques like Conditional Random Fields (CRFs) provide a accurate, elegant and principled framework for tackling these tasks. Given the inherent noise in real-world sources, it is important to capture the uncertainty of the above operations via imprecise data models. CRFs provide a sound probability distribution over extractions but are not easy to represent and query in a relational framework. We present methods of approximating this distribution to query-friendly row and column uncertainty models. Finally, we present models for representing the uncertainty of de-duplication and algorithms for various Top-K count queries on imprecise duplicates.

Eukaryotic RNA polymerase subunit RPB8 is a new relative of the OB family.

PubMed

Krapp, S; Kelly, G; Reischl, J; Weinzierl, R O; Matthews, S

1998-02-01

RNA polymerase II subunit RPB8 is an essential subunit that is highly conserved throughout eukaryotic evolution and is present in all three types of nuclear RNA polymerases. We report the first high resolution structural insight into eukaryotic RNA polymerase architecture with the solution structure of RPB8 from Saccharomyces cerevisiae. It consists of an eight stranded, antiparallel beta-barrel, four short helical regions and a large, unstructured omega-loop. The strands are connected in classic Greek-key fashion. The overall topology is unusual and contains a striking C2 rotational symmetry. Furthermore, it is most likely a novel associate of the oligonucleotide/oligosaccharide (OB) binding protein class.

Robust and efficient overset grid assembly for partitioned unstructured meshes

NASA Astrophysics Data System (ADS)

Roget, Beatrice; Sitaraman, Jayanarayanan

2014-03-01

This paper presents a method to perform efficient and automated Overset Grid Assembly (OGA) on a system of overlapping unstructured meshes in a parallel computing environment where all meshes are partitioned into multiple mesh-blocks and processed on multiple cores. The main task of the overset grid assembler is to identify, in parallel, among all points in the overlapping mesh system, at which points the flow solution should be computed (field points), interpolated (receptor points), or ignored (hole points). Point containment search or donor search, an algorithm to efficiently determine the cell that contains a given point, is the core procedure necessary for accomplishing this task. Donor search is particularly challenging for partitioned unstructured meshes because of the complex irregular boundaries that are often created during partitioning.

Boundary-Layer Stability Analysis of the Mean Flows Obtained Using Unstructured Grids

NASA Technical Reports Server (NTRS)

Liao, Wei; Malik, Mujeeb R.; Lee-Rausch, Elizabeth M.; Li, Fei; Nielsen, Eric J.; Buning, Pieter G.; Chang, Chau-Lyan; Choudhari, Meelan M.

2012-01-01

Boundary-layer stability analyses of mean flows extracted from unstructured-grid Navier- Stokes solutions have been performed. A procedure has been developed to extract mean flow profiles from the FUN3D unstructured-grid solutions. Extensive code-to-code validations have been performed by comparing the extracted mean ows as well as the corresponding stability characteristics to the predictions based on structured-grid solutions. Comparisons are made on a range of problems from a simple at plate to a full aircraft configuration-a modified Gulfstream-III with a natural laminar flow glove. The future aim of the project is to extend the adjoint-based design capability in FUN3D to include natural laminar flow and laminar flow control by integrating it with boundary-layer stability analysis codes, such as LASTRAC.

Mixed Element Type Unstructured Grid Generation for Viscous Flow Applications

NASA Technical Reports Server (NTRS)

Marcum, David L.; Gaither, J. Adam

2000-01-01

A procedure is presented for efficient generation of high-quality unstructured grids suitable for CFD simulation of high Reynolds number viscous flow fields. Layers of anisotropic elements are generated by advancing along prescribed normals from solid boundaries. The points are generated such that either pentahedral or tetrahedral elements with an implied connectivity can be be directly recovered. As points are generated they are temporarily attached to a volume triangulation of the boundary points. This triangulation allows efficient local search algorithms to be used when checking merging layers, The existing advancing-front/local-reconnection procedure is used to generate isotropic elements outside of the anisotropic region. Results are presented for a variety of applications. The results demonstrate that high-quality anisotropic unstructured grids can be efficiently and consistently generated for complex configurations.

Yeast prion architecture explains how proteins can be genes

NASA Astrophysics Data System (ADS)

Wickner, Reed

2013-03-01

Prions (infectious proteins) transmit information without an accompanying DNA or RNA. Most yeast prions are self-propagating amyloids that inactivate a normally functional protein. A single protein can become any of several prion variants, with different manifestations due to different amyloid structures. We showed that the yeast prion amyloids of Ure2p, Sup35p and Rnq1p are folded in-register parallel beta sheets using solid state NMR dipolar recoupling experiments, mass-per-filament-length measurements, and filament diameter measurements. The extent of beta sheet structure, measured by chemical shifts in solid-state NMR and acquired protease-resistance on amyloid formation, combined with the measured filament diameters, imply that the beta sheets must be folded along the long axis of the filament. We speculate that prion variants of a single protein sequence differ in the location of these folds. Favorable interactions between identical side chains must hold these structures in-register. The same interactions must guide an unstructured monomer joining the end of a filament to assume the same conformation as molecules already in the filament, with the turns at the same locations. In this way, a protein can template its own conformation, in analogy to the ability of a DNA molecule to template its sequence by specific base-pairing. Bldg. 8, Room 225, NIH, 8 Center Drive MSC 0830, Bethesda, MD 20892-0830, wickner@helix.nih.gov, 301-496-3452

Implementing the LIM code: the structural basis for cell type-specific assembly of LIM-homeodomain complexes

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

Bhati, Mugdha; Lee, Christopher; Nancarrow, Amy L.

2008-09-03

LIM-homeodomain (LIM-HD) transcription factors form a combinatorial 'LIM code' that contributes to the specification of cell types. In the ventral spinal cord, the binary LIM homeobox protein 3 (Lhx3)/LIM domain-binding protein 1 (Ldb1) complex specifies the formation of V2 interneurons. The additional expression of islet-1 (Isl1) in adjacent cells instead specifies the formation of motor neurons through assembly of a ternary complex in which Isl1 contacts both Lhx3 and Ldb1, displacing Lhx3 as the binding partner of Ldb1. However, little is known about how this molecular switch occurs. Here, we have identified the 30-residue Lhx3-binding domain on Isl1 (Isl1{sub LBD}).more » Although the LIM interaction domain of Ldb1 (Ldb1{sub LID}) and Isl1{sub LBD} share low levels of sequence homology, X-ray and NMR structures reveal that they bind Lhx3 in an identical manner, that is, Isl1{sub LBD} mimics Ldb1{sub LID}. These data provide a structural basis for the formation of cell type-specific protein-protein interactions in which unstructured linear motifs with diverse sequences compete to bind protein partners. The resulting alternate protein complexes can target different genes to regulate key biological events.« less

A Group 6 Late Embryogenesis Abundant Protein from Common Bean Is a Disordered Protein with Extended Helical Structure and Oligomer-forming Properties*

PubMed Central

Rivera-Najera, Lucero Y.; Saab-Rincón, Gloria; Battaglia, Marina; Amero, Carlos; Pulido, Nancy O.; García-Hernández, Enrique; Solórzano, Rosa M.; Reyes, José L.; Covarrubias, Alejandra A.

2014-01-01

Late embryogenesis-abundant proteins accumulate to high levels in dry seeds. Some of them also accumulate in response to water deficit in vegetative tissues, which leads to a remarkable association between their presence and low water availability conditions. A major sub-group of these proteins, also known as typical LEA proteins, shows high hydrophilicity and a high percentage of glycine and other small amino acid residues, distinctive physicochemical properties that predict a high content of structural disorder. Although all typical LEA proteins share these characteristics, seven groups can be distinguished by sequence similarity, indicating structural and functional diversity among them. Some of these groups have been extensively studied; however, others require a more detailed analysis to advance in their functional understanding. In this work, we report the structural characterization of a group 6 LEA protein from a common bean (Phaseolus vulgaris L.) (PvLEA6) by circular dichroism and nuclear magnetic resonance showing that it is a disordered protein in aqueous solution. Using the same techniques, we show that despite its unstructured nature, the addition of trifluoroethanol exhibited an intrinsic potential in this protein to gain helicity. This property was also promoted by high osmotic potentials or molecular crowding. Furthermore, we demonstrate that PvLEA6 protein is able to form soluble homo-oligomeric complexes that also show high levels of structural disorder. The association between PvLEA6 monomers to form dimers was shown to occur in plant cells by bimolecular fluorescence complementation, pointing to the in vivo functional relevance of this association. PMID:25271167

Simulation of Unsteady Flows Using an Unstructured Navier-Stokes Solver on Moving and Stationary Grids

NASA Technical Reports Server (NTRS)

Biedron, Robert T.; Vatsa, Veer N.; Atkins, Harold L.

2005-01-01

We apply an unsteady Reynolds-averaged Navier-Stokes (URANS) solver for unstructured grids to unsteady flows on moving and stationary grids. Example problems considered are relevant to active flow control and stability and control. Computational results are presented using the Spalart-Allmaras turbulence model and are compared to experimental data. The effect of grid and time-step refinement are examined.

Divergence-free MHD on unstructured meshes using high order finite volume schemes based on multidimensional Riemann solvers

NASA Astrophysics Data System (ADS)

Balsara, Dinshaw S.; Dumbser, Michael

2015-10-01

Several advances have been reported in the recent literature on divergence-free finite volume schemes for Magnetohydrodynamics (MHD). Almost all of these advances are restricted to structured meshes. To retain full geometric versatility, however, it is also very important to make analogous advances in divergence-free schemes for MHD on unstructured meshes. Such schemes utilize a staggered Yee-type mesh, where all hydrodynamic quantities (mass, momentum and energy density) are cell-centered, while the magnetic fields are face-centered and the electric fields, which are so useful for the time update of the magnetic field, are centered at the edges. Three important advances are brought together in this paper in order to make it possible to have high order accurate finite volume schemes for the MHD equations on unstructured meshes. First, it is shown that a divergence-free WENO reconstruction of the magnetic field can be developed for unstructured meshes in two and three space dimensions using a classical cell-centered WENO algorithm, without the need to do a WENO reconstruction for the magnetic field on the faces. This is achieved via a novel constrained L2-projection operator that is used in each time step as a postprocessor of the cell-centered WENO reconstruction so that the magnetic field becomes locally and globally divergence free. Second, it is shown that recently-developed genuinely multidimensional Riemann solvers (called MuSIC Riemann solvers) can be used on unstructured meshes to obtain a multidimensionally upwinded representation of the electric field at each edge. Third, the above two innovations work well together with a high order accurate one-step ADER time stepping strategy, which requires the divergence-free nonlinear WENO reconstruction procedure to be carried out only once per time step. The resulting divergence-free ADER-WENO schemes with MuSIC Riemann solvers give us an efficient and easily-implemented strategy for divergence-free MHD on unstructured meshes. Several stringent two- and three-dimensional problems are shown to work well with the methods presented here.

The UGRID Reader - A ParaView Plugin for the Visualization of Unstructured Climate Model Data in NetCDF Format

NASA Astrophysics Data System (ADS)

Brisc, Felicia; Vater, Stefan; Behrens, Joern

2016-04-01

We present the UGRID Reader, a visualization software component that implements the UGRID Conventions into Paraview. It currently supports the reading and visualization of 2D unstructured triangular, quadrilateral and mixed triangle/quadrilateral meshes, while the data can be defined per cell or per vertex. The Climate and Forecast Metadata Conventions (CF Conventions) have been set for many years as the standard framework for climate data written in NetCDF format. While they allow storing unstructured data simply as data defined at a series of points, they do not currently address the topology of the underlying unstructured mesh. However, it is often necessary to have additional mesh topology information, i.e. is it a one dimensional network, a 2D triangular mesh or a flexible mixed triangle/quadrilateral mesh, a 2D mesh with vertical layers, or a fully unstructured 3D mesh. The UGRID Conventions proposed by the UGRID Interoperability group are attempting to fill in this void by extending the CF Conventions with topology specifications. As the UGRID Conventions are increasingly popular with an important subset of the CF community, they warrant the development of a customized tool for the visualization and exploration of UGRID-conforming data. The implementation of the UGRID Reader has been designed corresponding to the ParaView plugin architecture. This approach allowed us to tap into the powerful reading and rendering capabilities of ParaView, while the reader is easy to install. We aim at parallelism to be able to process large data sets. Furthermore, our current application of the reader is the visualization of higher order simulation output which demands for a special representation of the data within a cell.

Analysis of Translocation-Competent Secretory Proteins by HDX-MS.

PubMed

Tsirigotaki, A; Papanastasiou, M; Trelle, M B; Jørgensen, T J D; Economou, A

2017-01-01

Protein folding is an intricate and precise process in living cells. Most exported proteins evade cytoplasmic folding, become targeted to the membrane, and then trafficked into/across membranes. Their targeting and translocation-competent states are nonnatively folded. However, once they reach the appropriate cellular compartment, they can fold to their native states. The nonnative states of preproteins remain structurally poorly characterized since increased disorder, protein sizes, aggregation propensity, and the observation timescale are often limiting factors for typical structural approaches such as X-ray crystallography and NMR. Here, we present an alternative approach for the in vitro analysis of nonfolded translocation-competent protein states and their comparison with their native states. We make use of hydrogen/deuterium exchange coupled with mass spectrometry (HDX-MS), a method based on differentiated isotope exchange rates in structured vs unstructured protein states/regions, and highly dynamic vs more rigid regions. We present a complete structural characterization pipeline, starting from the preparation of the polypeptides to data analysis and interpretation. Proteolysis and mass spectrometric conditions for the analysis of the labeled proteins are discussed, followed by the analysis and interpretation of HDX-MS data. We highlight the suitability of HDX-MS for identifying short structured regions within otherwise highly flexible protein states, as illustrated by an exported protein example, experimentally tested in our lab. Finally, we discuss statistical analysis in comparative HDX-MS. The protocol is applicable to any protein and protein size, exhibiting slow or fast loss of translocation competence. It could be easily adapted to more complex assemblies, such as the interaction of chaperones with nonnative protein states. © 2017 Elsevier Inc. All rights reserved.

A new multiscale air quality transport model (Fluidity, 4.1.9) using fully unstructured anisotropic adaptive mesh technology

NASA Astrophysics Data System (ADS)

Zheng, J.; Zhu, J.; Wang, Z.; Fang, F.; Pain, C. C.; Xiang, J.

2015-06-01

A new anisotropic hr-adaptive mesh technique has been applied to modelling of multiscale transport phenomena, which is based on a discontinuous Galerkin/control volume discretization on unstructured meshes. Over existing air quality models typically based on static-structured grids using a locally nesting technique, the advantage of the anisotropic hr-adaptive model has the ability to adapt the mesh according to the evolving pollutant distribution and flow features. That is, the mesh resolution can be adjusted dynamically to simulate the pollutant transport process accurately and effectively. To illustrate the capability of the anisotropic adaptive unstructured mesh model, three benchmark numerical experiments have been setup for two-dimensional (2-D) transport phenomena. Comparisons have been made between the results obtained using uniform resolution meshes and anisotropic adaptive resolution meshes.

Discrete Adjoint-Based Design Optimization of Unsteady Turbulent Flows on Dynamic Unstructured Grids

NASA Technical Reports Server (NTRS)

Nielsen, Eric J.; Diskin, Boris; Yamaleev, Nail K.

2009-01-01

An adjoint-based methodology for design optimization of unsteady turbulent flows on dynamic unstructured grids is described. The implementation relies on an existing unsteady three-dimensional unstructured grid solver capable of dynamic mesh simulations and discrete adjoint capabilities previously developed for steady flows. The discrete equations for the primal and adjoint systems are presented for the backward-difference family of time-integration schemes on both static and dynamic grids. The consistency of sensitivity derivatives is established via comparisons with complex-variable computations. The current work is believed to be the first verified implementation of an adjoint-based optimization methodology for the true time-dependent formulation of the Navier-Stokes equations in a practical computational code. Large-scale shape optimizations are demonstrated for turbulent flows over a tiltrotor geometry and a simulated aeroelastic motion of a fighter jet.

Visualizing unstructured patient data for assessing diagnostic and therapeutic history.

PubMed

Deng, Yihan; Denecke, Kerstin

2014-01-01

Having access to relevant patient data is crucial for clinical decision making. The data is often documented in unstructured texts and collected in the electronic health record. In this paper, we evaluate an approach to visualize information extracted from clinical documents by means of tag cloud. Tag clouds will be generated using a bag of word approach and by exploiting part of speech tags. For a real word data set comprising radiological reports, pathological reports and surgical operation reports, tag clouds are generated and a questionnaire-based study is conducted as evaluation. Feedback from the physicians shows that the tag cloud visualization is an effective and rapid approach to represent relevant parts of unstructured patient data. To handle the different medical narratives, we have summarized several possible improvements according to the user feedback and evaluation results.

The computation of three-dimensional flows using unstructured grids

NASA Technical Reports Server (NTRS)

Morgan, K.; Peraire, J.; Peiro, J.; Hassan, O.

1991-01-01

A general method is described for automatically discretizing, into unstructured assemblies of tetrahedra, the three-dimensional solution domains of complex shape which are of interest in practical computational aerodynamics. An algorithm for the solution of the compressible Euler equations which can be implemented on such general unstructured tetrahedral grids is described. This is an explicit cell-vertex scheme which follows a general Taylor-Galerkin philosophy. The approach is employed to compute a transonic inviscid flow over a standard wing and the results are shown to compare favorably with experimental observations. As a more practical demonstration, the method is then applied to the analysis of inviscid flow over a complete modern fighter configuration. The effect of using mesh adaptivity is illustrated when the method is applied to the solution of high speed flow in an engine inlet.

Studies of Plasma Instabilities using Unstructured Discontinuous Galerkin Method with the Two-Fluid Plasma Model

NASA Astrophysics Data System (ADS)

Song, Yang; Srinivasan, Bhuvana

2017-10-01

The discontinuous Galerkin (DG) method has the advantage of resolving shocks and sharp gradients that occur in neutral fluids and plasmas. An unstructured DG code has been developed in this work to study plasma instabilities using the two-fluid plasma model. Unstructured meshes are known to produce small and randomized grid errors compared to traditional structured meshes. Computational tests for Rayleigh-Taylor instabilities in radially-converging flows are performed using the MHD model. Choice of grid geometry is not obvious for simulations of instabilities in these circular configurations. Comparisons of the effects for different grids are made. A 2D magnetic nozzle simulation using the two-fluid plasma model is also performed. A vacuum boundary condition technique is applied to accurately solve the Riemann problem on the edge of the plume.

Algorithms and semantic infrastructure for mutation impact extraction and grounding.

PubMed

Laurila, Jonas B; Naderi, Nona; Witte, René; Riazanov, Alexandre; Kouznetsov, Alexandre; Baker, Christopher J O

2010-12-02

Mutation impact extraction is a hitherto unaccomplished task in state of the art mutation extraction systems. Protein mutations and their impacts on protein properties are hidden in scientific literature, making them poorly accessible for protein engineers and inaccessible for phenotype-prediction systems that currently depend on manually curated genomic variation databases. We present the first rule-based approach for the extraction of mutation impacts on protein properties, categorizing their directionality as positive, negative or neutral. Furthermore protein and mutation mentions are grounded to their respective UniProtKB IDs and selected protein properties, namely protein functions to concepts found in the Gene Ontology. The extracted entities are populated to an OWL-DL Mutation Impact ontology facilitating complex querying for mutation impacts using SPARQL. We illustrate retrieval of proteins and mutant sequences for a given direction of impact on specific protein properties. Moreover we provide programmatic access to the data through semantic web services using the SADI (Semantic Automated Discovery and Integration) framework. We address the problem of access to legacy mutation data in unstructured form through the creation of novel mutation impact extraction methods which are evaluated on a corpus of full-text articles on haloalkane dehalogenases, tagged by domain experts. Our approaches show state of the art levels of precision and recall for Mutation Grounding and respectable level of precision but lower recall for the task of Mutant-Impact relation extraction. The system is deployed using text mining and semantic web technologies with the goal of publishing to a broad spectrum of consumers.

Learning Long-Range Vision for an Offroad Robot

DTIC Science & Technology

2008-09-01

robot to perceive and navigate in an unstructured natural world is a difficult task. Without learning, navigation systems are short-range and extremely...unsupervised or weakly supervised learning methods are necessary for training general feature representations for natural scenes. The process was...the world looked dark, and Legos when I was weary. iii ABSTRACT Teaching a robot to perceive and navigate in an unstructured natural world is a

WENO schemes on arbitrary mixed-element unstructured meshes in three space dimensions

NASA Astrophysics Data System (ADS)

Tsoutsanis, P.; Titarev, V. A.; Drikakis, D.

2011-02-01

The paper extends weighted essentially non-oscillatory (WENO) methods to three dimensional mixed-element unstructured meshes, comprising tetrahedral, hexahedral, prismatic and pyramidal elements. Numerical results illustrate the convergence rates and non-oscillatory properties of the schemes for various smooth and discontinuous solutions test cases and the compressible Euler equations on various types of grids. Schemes of up to fifth order of spatial accuracy are considered.

Thermal Protection System Cavity Heating for Simplified and Actual Geometries Using Computational Fluid Dynamics Simulations with Unstructured Grids

NASA Technical Reports Server (NTRS)

McCloud, Peter L.

2010-01-01

Thermal Protection System (TPS) Cavity Heating is predicted using Computational Fluid Dynamics (CFD) on unstructured grids for both simplified cavities and actual cavity geometries. Validation was performed using comparisons to wind tunnel experimental results and CFD predictions using structured grids. Full-scale predictions were made for simplified and actual geometry configurations on the Space Shuttle Orbiter in a mission support timeframe.

Implementation of a parallel unstructured Euler solver on the CM-5

NASA Technical Reports Server (NTRS)

Morano, Eric; Mavriplis, D. J.

1995-01-01

An efficient unstructured 3D Euler solver is parallelized on a Thinking Machine Corporation Connection Machine 5, distributed memory computer with vectoring capability. In this paper, the single instruction multiple data (SIMD) strategy is employed through the use of the CM Fortran language and the CMSSL scientific library. The performance of the CMSSL mesh partitioner is evaluated and the overall efficiency of the parallel flow solver is discussed.

Unstructured grids for sonic-boom analysis

NASA Technical Reports Server (NTRS)

Fouladi, Kamran

1993-01-01

A fast and efficient unstructured grid scheme is evaluated for sonic-boom applications. The scheme is used to predict the near-field pressure signatures of a body of revolution at several body lengths below the configuration, and those results are compared with experimental data. The introduction of the 'sonic-boom grid topology' to this scheme make it well suited for sonic-boom applications, thus providing an alternative to conventional multiblock structured grid schemes.

A perspective on unstructured grid flow solvers

NASA Technical Reports Server (NTRS)

Venkatakrishnan, V.

1995-01-01

This survey paper assesses the status of compressible Euler and Navier-Stokes solvers on unstructured grids. Different spatial and temporal discretization options for steady and unsteady flows are discussed. The integration of these components into an overall framework to solve practical problems is addressed. Issues such as grid adaptation, higher order methods, hybrid discretizations and parallel computing are briefly discussed. Finally, some outstanding issues and future research directions are presented.

EMPHASIS/Nevada UTDEM user guide. Version 2.0.

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

Turner, C. David; Seidel, David Bruce; Pasik, Michael Francis

The Unstructured Time-Domain ElectroMagnetics (UTDEM) portion of the EMPHASIS suite solves Maxwell's equations using finite-element techniques on unstructured meshes. This document provides user-specific information to facilitate the use of the code for applications of interest. UTDEM is a general-purpose code for solving Maxwell's equations on arbitrary, unstructured tetrahedral meshes. The geometries and the meshes thereof are limited only by the patience of the user in meshing and by the available computing resources for the solution. UTDEM solves Maxwell's equations using finite-element method (FEM) techniques on tetrahedral elements using vector, edge-conforming basis functions. EMPHASIS/Nevada Unstructured Time-Domain ElectroMagnetic Particle-In-Cell (UTDEM PIC) ismore » a superset of the capabilities found in UTDEM. It adds the capability to simulate systems in which the effects of free charge are important and need to be treated in a self-consistent manner. This is done by integrating the equations of motion for macroparticles (a macroparticle is an object that represents a large number of real physical particles, all with the same position and momentum) being accelerated by the electromagnetic forces upon the particle (Lorentz force). The motion of these particles results in a current, which is a source for the fields in Maxwell's equations.« less

Structure and dynamics of cationic membrane peptides and proteins: Insights from solid-state NMR

PubMed Central

Hong, Mei; Su, Yongchao

2011-01-01

Many membrane peptides and protein domains contain functionally important cationic Arg and Lys residues, whose insertion into the hydrophobic interior of the lipid bilayer encounters significant energy barriers. To understand how these cationic molecules overcome the free energy barrier to insert into the lipid membrane, we have used solid-state NMR spectroscopy to determine the membrane-bound topology of these peptides. A versatile array of solid-state NMR experiments now readily yields the conformation, dynamics, orientation, depth of insertion, and site-specific protein–lipid interactions of these molecules. We summarize key findings of several Arg-rich membrane peptides, including β-sheet antimicrobial peptides, unstructured cell-penetrating peptides, and the voltage-sensing helix of voltage-gated potassium channels. Our results indicate the central role of guanidinium-phosphate and guanidinium-water interactions in dictating the structural topology of these cationic molecules in the lipid membrane, which in turn account for the mechanisms of this functionally diverse class of membrane peptides. PMID:21344534

Insulin chains as efficient fusion tags for prokaryotic expression of short peptides.

PubMed

Deng, Ligang; Xue, Xiaoying; Shen, Cangjie; Song, Xiaohan; Wang, Chunyang; Wang, Nan

2017-10-01

Insulin chains are usually expressed in Escherichia coli as fusion proteins with different tags, including various low molecular weight peptide tags. The objective of this study was to determine if insulin chains could facilitate the recombinant expression of other target proteins, with an emphasis on low molecular weight peptides. A series of short peptides were fused to mini-proinsulin, chain B or chain A, and induced for expression in Escherichia coli. All the tested peptides including glucagon-like peptide 1 (GLP-1), a C-terminal extended GLP-1, oxyntomodulin, enfuvirtide, linaclotide, and an unstructured artificial peptide were expressed with reasonable yields, identified by Tricine-SDS-PAGE and immunoblotting. All recombinant products were expressed in inclusion bodies. The effective accumulation of products was largely attributed to the insoluble expression induced by fusion with insulin chains, and was confirmed by the fusion expression of transthyretin. Insulin chains thus show promise as efficient fusion tags for mass production of heterologous peptides in prokaryotes. Copyright © 2017 Elsevier Inc. All rights reserved.

Diaphragm Plasticity in Aging and Disease: Therapies for Muscle Weakness go from Strength to Strength.

PubMed

Greising, Sarah M; Ottenheijm, Coen A C; O'Halloran, Ken D; Barreiro, Esther

2018-04-19

The diaphragm is the main inspiratory muscle and is required to be highly active throughout the lifespan. The diaphragm muscle must be able to produce and sustain various behaviors that range from ventilatory to non-ventilatory such as those required for airway maintenance and clearance. Throughout the lifespan various circumstances and conditions may affect the ability of the diaphragm muscle to generate requisite forces and in turn the diaphragm muscle may undergo significant weakness and dysfunction. For example, hypoxic stress, critical illness, cancer cachexia, chronic obstructive pulmonary disorder (COPD), and age-related sarcopenia all represent conditions in which significant diaphragm muscle dysfunction exits. This perspective review article presents several interesting topics involving diaphragm plasticity in aging and disease that were presented at the International Union of Physiological Sciences (IUPS) Conference in 2017.This review seeks to maximize the broad and collective research impact on diaphragm muscle dysfunction in the search for transformative treatment approaches to improve the diaphragm muscle health during aging and disease.

Atomistic structural ensemble refinement reveals non-native structure stabilizes a sub-millisecond folding intermediate of CheY

DOE PAGES

Shi, Jade; Nobrega, R. Paul; Schwantes, Christian; ...

2017-03-08

The dynamics of globular proteins can be described in terms of transitions between a folded native state and less-populated intermediates, or excited states, which can play critical roles in both protein folding and function. Excited states are by definition transient species, and therefore are difficult to characterize using current experimental techniques. We report an atomistic model of the excited state ensemble of a stabilized mutant of an extensively studied flavodoxin fold protein CheY. We employed a hybrid simulation and experimental approach in which an aggregate 42 milliseconds of all-atom molecular dynamics were used as an informative prior for the structuremore » of the excited state ensemble. The resulting prior was then refined against small-angle X-ray scattering (SAXS) data employing an established method (EROS). The most striking feature of the resulting excited state ensemble was an unstructured N-terminus stabilized by non-native contacts in a conformation that is topologically simpler than the native state. We then predict incisive single molecule FRET experiments, using these results, as a means of model validation. Our study demonstrates the paradigm of uniting simulation and experiment in a statistical model to study the structure of protein excited states and rationally design validating experiments.« less

Atomistic structural ensemble refinement reveals non-native structure stabilizes a sub-millisecond folding intermediate of CheY

NASA Astrophysics Data System (ADS)

Shi, Jade; Nobrega, R. Paul; Schwantes, Christian; Kathuria, Sagar V.; Bilsel, Osman; Matthews, C. Robert; Lane, T. J.; Pande, Vijay S.

2017-03-01

The dynamics of globular proteins can be described in terms of transitions between a folded native state and less-populated intermediates, or excited states, which can play critical roles in both protein folding and function. Excited states are by definition transient species, and therefore are difficult to characterize using current experimental techniques. Here, we report an atomistic model of the excited state ensemble of a stabilized mutant of an extensively studied flavodoxin fold protein CheY. We employed a hybrid simulation and experimental approach in which an aggregate 42 milliseconds of all-atom molecular dynamics were used as an informative prior for the structure of the excited state ensemble. This prior was then refined against small-angle X-ray scattering (SAXS) data employing an established method (EROS). The most striking feature of the resulting excited state ensemble was an unstructured N-terminus stabilized by non-native contacts in a conformation that is topologically simpler than the native state. Using these results, we then predict incisive single molecule FRET experiments as a means of model validation. This study demonstrates the paradigm of uniting simulation and experiment in a statistical model to study the structure of protein excited states and rationally design validating experiments.

Kinetic analysis and mathematical modeling of growth parameters of Lactobacillus plantarum in protein-rich isolates from tomato seed.

PubMed

Mechmeche, Manel; Kachouri, Faten; Yaghlane, Hana B; Ksontini, Hamida; Setti, Khaoula; Hamdi, Moktar

2017-03-01

The aim of the present study was to evaluate the applicability of using protein-rich isolates from tomato seed as a sole source of nutrition for the growth of lactic acid bacteria. Unstructured mathematical and logistic models were proposed to describe growth, pH drop, lactic acid production and nutriment consumption by Lactobacillus plantarum in whole and defatted isolates in order to compare their suitability for the production of a fermented beverage. These media have considerable good quantities of nutriment that allowed the growth of L. plantarum, after which the cell numbers begin to decline. The maximum biomass was observed in defatted isolate (1.42 g L -1 ) followed by the whole isolate (1.24 g L -1 ). The lactic acid increased by about 5.5 and 6.5 times respectively in whole and defatted protein isolates. However, significant nutriment consumption occurred during the growth phase as well as stationary phase. A reduction of 61.90% and 95.88% in sugar content, as well as 21.91% and 16.93% reduction in protein content were observed respectively in whole and defatted isolates. In most cases, the proposed models adequately describe the biochemical changes taking place during fermentation and are a promising approach for the formulation of tomato seed-based functional foods.

Measles Virus Hemagglutinin Protein Epitopes: The Basis of Antigenic Stability

PubMed Central

Tahara, Maino; Bürckert, Jean-Philippe; Kanou, Kazuhiko; Maenaka, Katsumi; Muller, Claude P.; Takeda, Makoto

2016-01-01

Globally eliminating measles using available vaccines is biologically feasible because the measles virus (MV) hemagglutinin (H) protein is antigenically stable. The H protein is responsible for receptor binding, and is the main target of neutralizing antibodies. The immunodominant epitope, known as the hemagglutinating and noose epitope, is located near the receptor-binding site (RBS). The RBS also contains an immunodominant epitope. Loss of receptor binding correlates with an escape from the neutralization by antibodies that target the epitope at RBS. Another neutralizing epitope is located near RBS and is shielded by an N-linked sugar in certain genotype strains. However, human sera from vaccinees and measles patients neutralized all MV strains with similar efficiencies, regardless of the N-linked sugar modification or mutations at these epitopes. Two other major epitopes exist at a distance from RBS. One has an unstructured flexible domain with a linear neutralizing epitope. When MV-H forms a tetramer (dimer of dimers), these epitopes may form the dimer-dimer interface, and one of the two epitopes may also interact with the F protein. The neutralization mechanisms of antibodies that recognize these epitopes may involve inhibiting the H-F interaction or blocking the fusion cascade after MV-H binds to its receptors. PMID:27490564

Modulation of mutant Huntingtin aggregates and toxicity by human myeloid leukemia factors.

PubMed

Banerjee, Manisha; Datta, Moumita; Bhattacharyya, Nitai P

2017-01-01

Increased poly glutamine (polyQ) stretch at N-terminal of Huntingtin (HTT) causes Huntington's disease. HTT interacts with large number of proteins, although the preference for such interactions with wild type or mutated HTT protein remains largely unknown. HYPK, an intrinsically unstructured protein chaperone and interactor of mutant HTT was found to interact with myeloid leukemia factor 1 (MLF1) and 2 (MLF2). To identify the role of these two proteins in mutant HTT mediated aggregate formation and toxicity in a cell model, both the proteins were found to preferentially interact with the mutated N-terminal HTT. They significantly reduced the number of cells containing mutant HTT aggregates and subsequent apoptosis in Neuro2A cells. Additionally, in FRAP assay, mobile fraction of mutant HTT aggregates was increased in the presence of MLF1 or MLF2. Further, MLF1 could release transcription factors like p53, CBP and CREB from mutant HTT aggregates. Moreover, in HeLa cell co-expressing mutant HTT exon1 and full length MLF1, p53 was released from the aggregates, leading to the recovery of the expression of the GADD45A transcript, a p53 regulated gene. Taking together, these results showed that MLF1 and MLF2 modulated the formation of aggregates and induction of apoptosis as well as the expressions of genes indirectly. Copyright © 2016 Elsevier Ltd. All rights reserved.

Reduced dimensionality (3,2)D NMR experiments and their automated analysis: implications to high-throughput structural studies on proteins.

PubMed

Reddy, Jithender G; Kumar, Dinesh; Hosur, Ramakrishna V

2015-02-01

Protein NMR spectroscopy has expanded dramatically over the last decade into a powerful tool for the study of their structure, dynamics, and interactions. The primary requirement for all such investigations is sequence-specific resonance assignment. The demand now is to obtain this information as rapidly as possible and in all types of protein systems, stable/unstable, soluble/insoluble, small/big, structured/unstructured, and so on. In this context, we introduce here two reduced dimensionality experiments – (3,2)D-hNCOcanH and (3,2)D-hNcoCAnH – which enhance the previously described 2D NMR-based assignment methods quite significantly. Both the experiments can be recorded in just about 2-3 h each and hence would be of immense value for high-throughput structural proteomics and drug discovery research. The applicability of the method has been demonstrated using alpha-helical bovine apo calbindin-D9k P43M mutant (75 aa) protein. Automated assignment of this data using AUTOBA has been presented, which enhances the utility of these experiments. The backbone resonance assignments so derived are utilized to estimate secondary structures and the backbone fold using Web-based algorithms. Taken together, we believe that the method and the protocol proposed here can be used for routine high-throughput structural studies of proteins. Copyright © 2014 John Wiley & Sons, Ltd.

Text mining patents for biomedical knowledge.

PubMed

Rodriguez-Esteban, Raul; Bundschus, Markus

2016-06-01

Biomedical text mining of scientific knowledge bases, such as Medline, has received much attention in recent years. Given that text mining is able to automatically extract biomedical facts that revolve around entities such as genes, proteins, and drugs, from unstructured text sources, it is seen as a major enabler to foster biomedical research and drug discovery. In contrast to the biomedical literature, research into the mining of biomedical patents has not reached the same level of maturity. Here, we review existing work and highlight the associated technical challenges that emerge from automatically extracting facts from patents. We conclude by outlining potential future directions in this domain that could help drive biomedical research and drug discovery. Copyright © 2016 Elsevier Ltd. All rights reserved.

Expanded RNA-binding activities of mammalian Argonaute 2

PubMed Central

Tan, Grace S.; Garchow, Barry G.; Liu, Xuhang; Yeung, Jennifer; Morris, John P.; Cuellar, Trinna L.; McManus, Michael T.; Kiriakidou, Marianthi

2009-01-01

Mammalian Argonaute 2 (Ago2) protein associates with microRNAs (miRNAs) or small interfering RNAs (siRNAs) forming RNA-induced silencing complexes (RISCs/miRNPs). In the present work, we characterize the RNA-binding and nucleolytic activity of recombinant mouse Ago2. Our studies show that recombinant mouse Ago2 binds efficiently to miRNAs forming active RISC. Surprisingly, we find that recombinant mouse Ago2 forms active RISC using pre-miRNAs or long unstructured single stranded RNAs as guides. Furthermore, we demonstrate that, in vivo, endogenous human Ago2 binds directly to pre-miRNAs independently of Dicer, and that Ago2:pre-miRNA complexes are found both in the cytoplasm and in the nucleus of human cells. PMID:19808937

Proline-Rich Salivary Proteins Have Extended Conformations

PubMed Central

Boze, Hélène; Marlin, Thérèse; Durand, Dominique; Pérez, Javier; Vernhet, Aude; Canon, Francis; Sarni-Manchado, Pascale; Cheynier, Véronique; Cabane, Bernard

2010-01-01

Abstract Three basic proline-rich salivary proteins have been produced through the recombinant route. IB5 is a small basic proline-rich protein that is involved in the binding of plant tannins in the oral cavity. II-1 is a larger protein with a closely related backbone; it is glycosylated, and it is also able to bind plant tannins. II-1ng has the same polypeptidic backbone as II-1, but it is not glycosylated. Small angle x-ray scattering experiments on dilute solutions of these proteins confirm that they are intrinsically disordered. IB5 and II-1ng can be described through a chain model including a persistence length and cross section. The measured radii of gyration (Rg = 27.9 and 41.0 ± 1 Å respectively) and largest distances (rmax = 110 and 155 ± 10 Å respectively) show that their average conformations are rather extended. The length of the statistical segment (twice the persistence length) is b = 30 Å, which is larger than the usual value (18 Å − 20 Å) for unstructured polypeptide chains. These characteristics are presumably related to the presence of polyproline helices within the polypeptidic backbones. For both proteins, the radius of gyration of the chain cross-section is Rc = 2.7 ± 0.2Å. The glycosylated protein II-1 has similar conformations but the presence of large polyoside sidegroups yields the structure of a branched macromolecule with the same hydrophobic backbone and hydrophilic branches. It is proposed that the unusually extended conformations of these proteins in solution facilitate the capture of plant tannins in the oral cavity. PMID:20643086

Non-Cooperative Group Decision Support Systems: Problems and Some Solutions.

DTIC Science & Technology

1986-09-01

appears that in these situations the 46 content of the problem and the structure of the problem is " fuzzy ." It requires an active cooperation between the...some unstructured parts will remain. This partial ’unstructurability’ is due to uncertainty, fuzziness , ignorance, and an inability to...according to the Analytic Hierarchy Process ( AHP ) technique (Gui, 1985). The AHP algorithm consists of the following steps; (i) Perform a pairwise comparison

A 3D Unstructured Mesh Euler Solver Based on the Fourth-Order CESE Method

DTIC Science & Technology

2013-06-01

Form 298 (Rev. 8-98) Prescribed by ANSI Std. 239.18 A 3D Unstructured Mesh Euler Solver Based on the Fourth-Order CESE Method David L. Bilyeu ∗1,2...Similarly, the fluxes, f x,y,z i , and their derivatives inside a SE are also discretized by the Taylor series expansion: ∂ Cfx ,y,zi ∂xI∂yJ∂zK∂tL = A

A 3-D CE/SE Navier-Stokes Solver With Unstructured Hexahedral Grid for Computation of Near Field Jet Screech Noise

NASA Technical Reports Server (NTRS)

Loh, Ching Y.; Himansu, Ananda; Hultgren, Lennart S.

2003-01-01

A 3-D space-time CE/SE Navier-Stokes solver using an unstructured hexahedral grid is described and applied to a circular jet screech noise computation. The present numerical results for an underexpanded jet, corresponding to a fully expanded Mach number of 1.42, capture the dominant and nonaxisymmetric 'B' screech mode and are generally in good agreement with existing experiments.

A New Approach to Parallel Dynamic Partitioning for Adaptive Unstructured Meshes

NASA Technical Reports Server (NTRS)

Heber, Gerd; Biswas, Rupak; Gao, Guang R.

1999-01-01

Classical mesh partitioning algorithms were designed for rather static situations, and their straightforward application in a dynamical framework may lead to unsatisfactory results, e.g., excessive data migration among processors. Furthermore, special attention should be paid to their amenability to parallelization. In this paper, a novel parallel method for the dynamic partitioning of adaptive unstructured meshes is described. It is based on a linear representation of the mesh using self-avoiding walks.

Three-dimensional unstructured grid refinement and optimization using edge-swapping

NASA Technical Reports Server (NTRS)

Gandhi, Amar; Barth, Timothy

1993-01-01

This paper presents a three-dimensional (3-D) 'edge-swapping method based on local transformations. This method extends Lawson's edge-swapping algorithm into 3-D. The 3-D edge-swapping algorithm is employed for the purpose of refining and optimizing unstructured meshes according to arbitrary mesh-quality measures. Several criteria including Delaunay triangulations are examined. Extensions from two to three dimensions of several known properties of Delaunay triangulations are also discussed.

PLUM: Parallel Load Balancing for Unstructured Adaptive Meshes. Degree awarded by Colorado Univ.

NASA Technical Reports Server (NTRS)

Oliker, Leonid

1998-01-01

Dynamic mesh adaption on unstructured grids is a powerful tool for computing large-scale problems that require grid modifications to efficiently resolve solution features. By locally refining and coarsening the mesh to capture physical phenomena of interest, such procedures make standard computational methods more cost effective. Unfortunately, an efficient parallel implementation of these adaptive methods is rather difficult to achieve, primarily due to the load imbalance created by the dynamically-changing nonuniform grid. This requires significant communication at runtime, leading to idle processors and adversely affecting the total execution time. Nonetheless, it is generally thought that unstructured adaptive- grid techniques will constitute a significant fraction of future high-performance supercomputing. Various dynamic load balancing methods have been reported to date; however, most of them either lack a global view of loads across processors or do not apply their techniques to realistic large-scale applications.

An Exact Dual Adjoint Solution Method for Turbulent Flows on Unstructured Grids

NASA Technical Reports Server (NTRS)

Nielsen, Eric J.; Lu, James; Park, Michael A.; Darmofal, David L.

2003-01-01

An algorithm for solving the discrete adjoint system based on an unstructured-grid discretization of the Navier-Stokes equations is presented. The method is constructed such that an adjoint solution exactly dual to a direct differentiation approach is recovered at each time step, yielding a convergence rate which is asymptotically equivalent to that of the primal system. The new approach is implemented within a three-dimensional unstructured-grid framework and results are presented for inviscid, laminar, and turbulent flows. Improvements to the baseline solution algorithm, such as line-implicit relaxation and a tight coupling of the turbulence model, are also presented. By storing nearest-neighbor terms in the residual computation, the dual scheme is computationally efficient, while requiring twice the memory of the flow solution. The scheme is expected to have a broad impact on computational problems related to design optimization as well as error estimation and grid adaptation efforts.

Domain Decomposition By the Advancing-Partition Method for Parallel Unstructured Grid Generation

NASA Technical Reports Server (NTRS)

Pirzadeh, Shahyar Z.; Zagaris, George

2009-01-01

A new method of domain decomposition has been developed for generating unstructured grids in subdomains either sequentially or using multiple computers in parallel. Domain decomposition is a crucial and challenging step for parallel grid generation. Prior methods are generally based on auxiliary, complex, and computationally intensive operations for defining partition interfaces and usually produce grids of lower quality than those generated in single domains. The new technique, referred to as "Advancing Partition," is based on the Advancing-Front method, which partitions a domain as part of the volume mesh generation in a consistent and "natural" way. The benefits of this approach are: 1) the process of domain decomposition is highly automated, 2) partitioning of domain does not compromise the quality of the generated grids, and 3) the computational overhead for domain decomposition is minimal. The new method has been implemented in NASA's unstructured grid generation code VGRID.

Unstructured viscous grid generation by advancing-front method

NASA Technical Reports Server (NTRS)

Pirzadeh, Shahyar

1993-01-01

A new method of generating unstructured triangular/tetrahedral grids with high-aspect-ratio cells is proposed. The method is based on new grid-marching strategy referred to as 'advancing-layers' for construction of highly stretched cells in the boundary layer and the conventional advancing-front technique for generation of regular, equilateral cells in the inviscid-flow region. Unlike the existing semi-structured viscous grid generation techniques, the new procedure relies on a totally unstructured advancing-front grid strategy resulting in a substantially enhanced grid flexibility and efficiency. The method is conceptually simple but powerful, capable of producing high quality viscous grids for complex configurations with ease. A number of two-dimensional, triangular grids are presented to demonstrate the methodology. The basic elements of the method, however, have been primarily designed with three-dimensional problems in mind, making it extendible for tetrahedral, viscous grid generation.

A Robust and Scalable Software Library for Parallel Adaptive Refinement on Unstructured Meshes

NASA Technical Reports Server (NTRS)

Lou, John Z.; Norton, Charles D.; Cwik, Thomas A.

1999-01-01

The design and implementation of Pyramid, a software library for performing parallel adaptive mesh refinement (PAMR) on unstructured meshes, is described. This software library can be easily used in a variety of unstructured parallel computational applications, including parallel finite element, parallel finite volume, and parallel visualization applications using triangular or tetrahedral meshes. The library contains a suite of well-designed and efficiently implemented modules that perform operations in a typical PAMR process. Among these are mesh quality control during successive parallel adaptive refinement (typically guided by a local-error estimator), parallel load-balancing, and parallel mesh partitioning using the ParMeTiS partitioner. The Pyramid library is implemented in Fortran 90 with an interface to the Message-Passing Interface (MPI) library, supporting code efficiency, modularity, and portability. An EM waveguide filter application, adaptively refined using the Pyramid library, is illustrated.

Discrete Adjoint-Based Design for Unsteady Turbulent Flows On Dynamic Overset Unstructured Grids

NASA Technical Reports Server (NTRS)

Nielsen, Eric J.; Diskin, Boris

2012-01-01

A discrete adjoint-based design methodology for unsteady turbulent flows on three-dimensional dynamic overset unstructured grids is formulated, implemented, and verified. The methodology supports both compressible and incompressible flows and is amenable to massively parallel computing environments. The approach provides a general framework for performing highly efficient and discretely consistent sensitivity analysis for problems involving arbitrary combinations of overset unstructured grids which may be static, undergoing rigid or deforming motions, or any combination thereof. General parent-child motions are also accommodated, and the accuracy of the implementation is established using an independent verification based on a complex-variable approach. The methodology is used to demonstrate aerodynamic optimizations of a wind turbine geometry, a biologically-inspired flapping wing, and a complex helicopter configuration subject to trimming constraints. The objective function for each problem is successfully reduced and all specified constraints are satisfied.

Parallel volume ray-casting for unstructured-grid data on distributed-memory architectures

NASA Technical Reports Server (NTRS)

Ma, Kwan-Liu

1995-01-01

As computing technology continues to advance, computational modeling of scientific and engineering problems produces data of increasing complexity: large in size and unstructured in shape. Volume visualization of such data is a challenging problem. This paper proposes a distributed parallel solution that makes ray-casting volume rendering of unstructured-grid data practical. Both the data and the rendering process are distributed among processors. At each processor, ray-casting of local data is performed independent of the other processors. The global image composing processes, which require inter-processor communication, are overlapped with the local ray-casting processes to achieve maximum parallel efficiency. This algorithm differs from previous ones in four ways: it is completely distributed, less view-dependent, reasonably scalable, and flexible. Without using dynamic load balancing, test results on the Intel Paragon using from two to 128 processors show, on average, about 60% parallel efficiency.

Population-level mating patterns and fluctuating asymmetry in swordtail hybrids

NASA Astrophysics Data System (ADS)

Culumber, Zachary W.; Rosenthal, Gil G.

2013-08-01

Morphological symmetry is a correlate of fitness-related traits or even a direct target of mate choice in a variety of taxa. In these taxa, when females discriminate among potential mates, increased selection on males should reduce fluctuating asymmetry (FA). Hybrid populations of the swordtails Xiphophorus birchmanni and Xiphophorus malinche vary from panmictic (unstructured) to highly structured, in which reproductive isolation is maintained among hybrids and parental species. We predicted that FA in flanking vertical bars used in sexual signalling should be lower in structured populations, where non-random mating patterns are observed. FA in vertical bars was markedly lower in structured populations than in parental and unstructured hybrid populations. There was no difference in FA between parentals and hybrids, suggesting that hybridisation does not directly affect FA. Rather, variation in FA likely results from contrasting mating patterns in unstructured and structured populations.

An effective lattice Boltzmann flux solver on arbitrarily unstructured meshes

NASA Astrophysics Data System (ADS)

Wu, Qi-Feng; Shu, Chang; Wang, Yan; Yang, Li-Ming

2018-05-01

The recently proposed lattice Boltzmann flux solver (LBFS) is a new approach for the simulation of incompressible flow problems. It applies the finite volume method (FVM) to discretize the governing equations, and the flux at the cell interface is evaluated by local reconstruction of lattice Boltzmann solution from macroscopic flow variables at cell centers. In the previous application of the LBFS, the structured meshes have been commonly employed, which may cause inconvenience for problems with complex geometries. In this paper, the LBFS is extended to arbitrarily unstructured meshes for effective simulation of incompressible flows. Two test cases, the lid-driven flow in a triangular cavity and flow around a circular cylinder, are carried out for validation. The obtained results are compared with the data available in the literature. Good agreement has been achieved, which demonstrates the effectiveness and reliability of the LBFS in simulating flows on arbitrarily unstructured meshes.

Workspace Safe Operation of a Force- or Impedance-Controlled Robot

NASA Technical Reports Server (NTRS)

Abdallah, Muhammad E. (Inventor); Hargrave, Brian (Inventor); Strawser, Philip A. (Inventor); Yamokoski, John D. (Inventor)

2013-01-01

A method of controlling a robotic manipulator of a force- or impedance-controlled robot within an unstructured workspace includes imposing a saturation limit on a static force applied by the manipulator to its surrounding environment, and may include determining a contact force between the manipulator and an object in the unstructured workspace, and executing a dynamic reflex when the contact force exceeds a threshold to thereby alleviate an inertial impulse not addressed by the saturation limited static force. The method may include calculating a required reflex torque to be imparted by a joint actuator to a robotic joint. A robotic system includes a robotic manipulator having an unstructured workspace and a controller that is electrically connected to the manipulator, and which controls the manipulator using force- or impedance-based commands. The controller, which is also disclosed herein, automatically imposes the saturation limit and may execute the dynamic reflex noted above.

Numerical approach for unstructured quantum key distribution

PubMed Central

Coles, Patrick J.; Metodiev, Eric M.; Lütkenhaus, Norbert

2016-01-01

Quantum key distribution (QKD) allows for communication with security guaranteed by quantum theory. The main theoretical problem in QKD is to calculate the secret key rate for a given protocol. Analytical formulas are known for protocols with symmetries, since symmetry simplifies the analysis. However, experimental imperfections break symmetries, hence the effect of imperfections on key rates is difficult to estimate. Furthermore, it is an interesting question whether (intentionally) asymmetric protocols could outperform symmetric ones. Here we develop a robust numerical approach for calculating the key rate for arbitrary discrete-variable QKD protocols. Ultimately this will allow researchers to study ‘unstructured' protocols, that is, those that lack symmetry. Our approach relies on transforming the key rate calculation to the dual optimization problem, which markedly reduces the number of parameters and hence the calculation time. We illustrate our method by investigating some unstructured protocols for which the key rate was previously unknown. PMID:27198739

Multi-Resolution Unstructured Grid-Generation for Geophysical Applications on the Sphere

NASA Technical Reports Server (NTRS)

Engwirda, Darren

2015-01-01

An algorithm for the generation of non-uniform unstructured grids on ellipsoidal geometries is described. This technique is designed to generate high quality triangular and polygonal meshes appropriate for general circulation modelling on the sphere, including applications to atmospheric and ocean simulation, and numerical weather predication. Using a recently developed Frontal-Delaunay-refinement technique, a method for the construction of high-quality unstructured ellipsoidal Delaunay triangulations is introduced. A dual polygonal grid, derived from the associated Voronoi diagram, is also optionally generated as a by-product. Compared to existing techniques, it is shown that the Frontal-Delaunay approach typically produces grids with near-optimal element quality and smooth grading characteristics, while imposing relatively low computational expense. Initial results are presented for a selection of uniform and non-uniform ellipsoidal grids appropriate for large-scale geophysical applications. The use of user-defined mesh-sizing functions to generate smoothly graded, non-uniform grids is discussed.

Assessment of the Unstructured Grid Software TetrUSS for Drag Prediction of the DLR-F4 Configuration

NASA Technical Reports Server (NTRS)

Pirzadeh, Shahyar Z.; Frink, Neal T.

2002-01-01

An application of the NASA unstructured grid software system TetrUSS is presented for the prediction of aerodynamic drag on a transport configuration. The paper briefly describes the underlying methodology and summarizes the results obtained on the DLR-F4 transport configuration recently presented in the first AIAA computational fluid dynamics (CFD) Drag Prediction Workshop. TetrUSS is a suite of loosely coupled unstructured grid CFD codes developed at the NASA Langley Research Center. The meshing approach is based on the advancing-front and the advancing-layers procedures. The flow solver employs a cell-centered, finite volume scheme for solving the Reynolds Averaged Navier-Stokes equations on tetrahedral grids. For the present computations, flow in the viscous sublayer has been modeled with an analytical wall function. The emphasis of the paper is placed on the practicality of the methodology for accurately predicting aerodynamic drag data.

A matrix-free implicit unstructured multigrid finite volume method for simulating structural dynamics and fluid structure interaction

NASA Astrophysics Data System (ADS)

Lv, X.; Zhao, Y.; Huang, X. Y.; Xia, G. H.; Su, X. H.

2007-07-01

A new three-dimensional (3D) matrix-free implicit unstructured multigrid finite volume (FV) solver for structural dynamics is presented in this paper. The solver is first validated using classical 2D and 3D cantilever problems. It is shown that very accurate predictions of the fundamental natural frequencies of the problems can be obtained by the solver with fast convergence rates. This method has been integrated into our existing FV compressible solver [X. Lv, Y. Zhao, et al., An efficient parallel/unstructured-multigrid preconditioned implicit method for simulating 3d unsteady compressible flows with moving objects, Journal of Computational Physics 215(2) (2006) 661-690] based on the immersed membrane method (IMM) [X. Lv, Y. Zhao, et al., as mentioned above]. Results for the interaction between the fluid and an immersed fixed-free cantilever are also presented to demonstrate the potential of this integrated fluid-structure interaction approach.

The phosphatidylinositol transfer protein RdgBβ binds 14-3-3 via its unstructured C-terminus, whereas its lipid-binding domain interacts with the integral membrane protein ATRAP (angiotensin II type I receptor-associated protein).

PubMed

Garner, Kathryn; Li, Michelle; Ugwuanya, Natalie; Cockcroft, Shamshad

2011-10-01

PITPs [PI (phosphatidylinositol) transfer proteins] bind and transfer PI between intracellular membranes and participate in many cellular processes including signalling, lipid metabolism and membrane traffic. The largely uncharacterized PITP RdgBβ (PITPNC1; retinal degeneration type B β), contains a long C-terminal disordered region following its defining N-terminal PITP domain. In the present study we report that the C-terminus contains two tandem phosphorylated binding sites (Ser(274) and Ser(299)) for 14-3-3. The C-terminus also contains PEST sequences which are shielded by 14-3-3 binding. Like many proteins containing PEST sequences, the levels of RdgBβ are regulated by proteolysis. RdgBβ is degraded with a half-life of 4 h following ubiquitination via the proteasome. A mutant RdgBβ which is unable to bind 14-3-3 is degraded even faster with a half-life of 2 h. In vitro, RdgBβ is 100-fold less active than PITPα for PI transfer, and RdgBβ proteins (wild-type and a mutant that cannot bind 14-3-3) expressed in COS-7 cells or endogenous proteins from heart cytosol do not exhibit transfer activity. When cells are treated with PMA, the PITP domain of RdgBβ interacts with the integral membrane protein ATRAP (angiotensin II type I receptor-associated protein; also known as AGTRAP) causing membrane recruitment. We suggest that RdgBβ executes its function following recruitment to membranes via its PITP domain and the C-terminal end of the protein could regulate entry to the hydrophobic cavity.

Comprehensive Phylogenetic Analysis Sheds Light on the Diversity and Origin of the MLO Family of Integral Membrane Proteins

PubMed Central

Kusch, Stefan; Pesch, Lina; Panstruga, Ralph

2016-01-01

Mildew resistance Locus O (MLO) proteins are polytopic integral membrane proteins that have long been considered as plant-specific and being primarily involved in plant–powdery mildew interactions. However, research in the past decade has revealed that MLO proteins diverged into a family with several clades whose members are associated with different physiological processes. We provide a largely increased dataset of MLO amino acid sequences, comprising nearly all major land plant lineages. Based on this comprehensive dataset, we defined seven phylogenetic clades and reconstructed the likely evolution of the MLO family in embryophytes. We further identified several MLO peptide motifs that are either conserved in all MLO proteins or confined to one or several clades, supporting the notion that clade-specific diversification of MLO functions is associated with particular sequence motifs. In baker’s yeast, some of these motifs are functionally linked to transmembrane (TM) transport of organic molecules and ions. In addition, we attempted to define the evolutionary origin of the MLO family and found that MLO-like proteins with highly diverse membrane topologies are present in green algae, but also in the distinctly related red algae (Rhodophyta), Amoebozoa, and Chromalveolata. Finally, we discovered several instances of putative fusion events between MLO proteins and different kinds of proteins. Such Rosetta stone-type hybrid proteins might be instructive for future analysis of potential MLO functions. Our findings suggest that MLO is an ancient protein that possibly evolved in unicellular photosynthetic eukaryotes, and consolidated in land plants with a conserved topology, comprising seven TM domains and an intrinsically unstructured C-terminus. PMID:26893454

Conformational transition of κ-casein in micellar environment: Insight from the tryptophan fluorescence

NASA Astrophysics Data System (ADS)

Mishra, Smruti; Meher, Geetanjali; Chakraborty, Hirak

2017-11-01

Intrinsically disordered proteins (IDPs) are under intense analysis due to their structural flexibility and importance in biological functions. Minuscule modulation in the microenvironment induces significant conformational changes in IDPs, and these non-native conformations of the IDPs often induce aggregation and cause cell death. Changes in the membrane composition often change the microenvironment, which promote conformational change and aggregation of IDPs. κ-Casein, an important milk protein, belongs to the class of IDPs containing net negative charges. In this present work, we have studied the interaction of κ-casein with cetyltrimethyl ammonium bromide (CTAB), a positively charged surfactant, utilizing various steady state fluorescence, time-resolved fluorescence and circular dichroism spectroscopy. Our results clearly indicate that κ-casein undergoes at least two conformational transitions in presence of various concentrations of CTAB. The intrinsically disordered κ-casein assumes a partially folded conformation at lower concentration of CTAB, which adopts an unstructured conformation at higher concentration of CTAB. The partially folded conformation of κ-casein at a lower CTAB concentration might be induced by the favorable electrostatic interaction between the positively charged surfactant headgroup and net negative charges of the protein, whereas surfactant nature of CTAB is being pronounced at higher concentration of CTAB.

Optical characterisation of three reference Dobsons in the ATMOZ Project - verification of G. M. B. Dobson's original specifications

NASA Astrophysics Data System (ADS)

Köhler, Ulf; Nevas, Saulius; McConville, Glen; Evans, Robert; Smid, Marek; Stanek, Martin; Redondas, Alberto; Schönenborn, Fritz

2018-04-01

Three reference Dobsons (regional standard Dobsons No. 064, Germany and No. 074, Czech Republic as well as the world standard No. 083, USA) were optically characterized at the Physikalisch-Technische Bundesanstalt (PTB) in Braunschweig in 2015 and at the Czech Metrology Institute (CMI) in Prague in 2016 within the EMRP ENV 059 project Traceability for atmospheric total column ozone. Slit functions and the related parameters of the instruments were measured and compared with G. M. B. Dobson's specifications in his handbook. All Dobsons show a predominantly good match of the slit functions and the peak (centroid) wavelengths with deviations between -0.11 and +0.12 nm and differences of the full width half maximum (FWHM) between 0.13 and 0.37 nm compared to the nominal values at the shorter wavelengths. Slightly larger deviations of the FWHMs from the nominal Dobson data, up to 1.22 nm, can be seen at the longer wavelengths, especially for the slit function of the long D-wavelength. However, differences between the effective absorption coefficients (EACs) for ozone derived using Dobson's nominal values of the optical parameters on one hand and these measured values on the other hand are not too large in the case of both old Bass-Paur (BP) and new IUP-ozone (Institut für Umweltphysik, University of Bremen) absorption cross sections. Their inclusion in the calculation of the total ozone column (TOC) leads to improvements of significantly less than ±1 % at the AD-wavelengths between -1 and -2 % at the CD-wavelengths pairs in the BP-scale. The effect on the TOC in the IUP-scale is somewhat larger at the AD-wavelengths, up to +1 % (D074), and smaller at the CD-wavelengths pair, from -0.44 to -1.5 %. Beside this positive effect gained from the data with higher metrological quality that is needed for trend analyses and satellite validation, it will be also possible to explain uncommon behaviours of field Dobsons during calibration services, especially when a newly developed transportable device TuPS (tuneable portable radiation source) from CMI proves its capability to provide similar results as the stationary setups in the laboratories of National Metrology Institutes. Then, the field Dobsons can be optically characterized as well during regular calibration campaigns. A corresponding publication will be prepared using the results of TuPS-based measurements of more than 10 Dobsons in field campaigns in 2017.

Third-order accurate conservative method on unstructured meshes for gasdynamic simulations

NASA Astrophysics Data System (ADS)

Shirobokov, D. A.

2017-04-01

A third-order accurate finite-volume method on unstructured meshes is proposed for solving viscous gasdynamic problems. The method is described as applied to the advection equation. The accuracy of the method is verified by computing the evolution of a vortex on meshes of various degrees of detail with variously shaped cells. Additionally, unsteady flows around a cylinder and a symmetric airfoil are computed. The numerical results are presented in the form of plots and tables.

EMPHASIS(TM)/Nevada UTDEM User Guide Version 2.1.1.

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

Turner, C. David; Pasik, Michael F.; Pointon, Timothy D.

The Unstructured Time - Domain ElectroMagnetics (UTDEM) portion of the EMPHASIS suite solves Maxwell's equations using finite - element techniques on unstructured meshes. This document provides user - specific information to facilitate the use of the code for ap plications of interest. Acknowledgement The authors would like to thank all of those individuals who have helped to bring EMPHASIS/Nevada to the point it is today, including Bill Bohnhoff, Rich Drake, and all of the NEVADA code team.

Unstructured Polyhedral Mesh Thermal Radiation Diffusion

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

Palmer, T.S.; Zika, M.R.; Madsen, N.K.

2000-07-27

Unstructured mesh particle transport and diffusion methods are gaining wider acceptance as mesh generation, scientific visualization and linear solvers improve. This paper describes an algorithm that is currently being used in the KULL code at Lawrence Livermore National Laboratory to solve the radiative transfer equations. The algorithm employs a point-centered diffusion discretization on arbitrary polyhedral meshes in 3D. We present the results of a few test problems to illustrate the capabilities of the radiation diffusion module.

Unstructured 3D Delaunay mesh generation applied to planes, trains and automobiles

NASA Technical Reports Server (NTRS)

Blake, Kenneth R.; Spragle, Gregory S.

1993-01-01

Technical issues associated with domain-tessellation production, including initial boundary node triangulation and volume mesh refinement, are presented for the 'TGrid' 3D Delaunay unstructured grid generation program. The approach employed is noted to be capable of preserving predefined triangular surface facets in the final tessellation. The capabilities of the approach are demonstrated by generating grids about an entire fighter aircraft configuration, a train, and a wind tunnel model of an automobile.

Solution algorithms for the two-dimensional Euler equations on unstructured meshes

NASA Technical Reports Server (NTRS)

Whitaker, D. L.; Slack, David C.; Walters, Robert W.

1990-01-01

The objective of the study was to analyze implicit techniques employed in structured grid algorithms for solving two-dimensional Euler equations and extend them to unstructured solvers in order to accelerate convergence rates. A comparison is made between nine different algorithms for both first-order and second-order accurate solutions. Higher-order accuracy is achieved by using multidimensional monotone linear reconstruction procedures. The discussion is illustrated by results for flow over a transonic circular arc.

elsA-Hybrid: an all-in-one structured/unstructured solver for the simulation of internal and external flows. Application to turbomachinery

NASA Astrophysics Data System (ADS)

de la Llave Plata, M.; Couaillier, V.; Le Pape, M.-C.; Marmignon, C.; Gazaix, M.

2013-03-01

This paper reports recent work on the extension of the multiblock structured solver elsA to deal with hybrid grids. The new hybrid-grid solver is called elsA-H (elsA-Hybrid), is based on the investigation of a new unstructured-grid module has been built within the original elsA CFD (computational fluid dynamics) system. The implementation benefits from the flexibility of the object-oriented design. The aim of elsA-H is to take advantage of the full potential of structured solvers and unstructured mesh generation by allowing any type of grid to be used within the same simulation process. The main challenge lies in the numerical treatment of the hybrid-grid interfaces where blocks of different type meet. In particular, one must pay attention to the transfer of information across these boundaries, so that the accuracy of the numerical scheme is preserved and flux conservation is guaranteed. In this paper, the numerical approach allowing to achieve this is presented. A comparison between the hybrid and the structured-grid methods is also carried out by considering a fully hexahedral multiblock mesh for which a few blocks have been transformed into unstructured. The performance of elsA-H for the simulation of internal flows will be demonstrated on a number of turbomachinery configurations.

Coronary artery disease risk assessment from unstructured electronic health records using text mining.

PubMed

Jonnagaddala, Jitendra; Liaw, Siaw-Teng; Ray, Pradeep; Kumar, Manish; Chang, Nai-Wen; Dai, Hong-Jie

2015-12-01

Coronary artery disease (CAD) often leads to myocardial infarction, which may be fatal. Risk factors can be used to predict CAD, which may subsequently lead to prevention or early intervention. Patient data such as co-morbidities, medication history, social history and family history are required to determine the risk factors for a disease. However, risk factor data are usually embedded in unstructured clinical narratives if the data is not collected specifically for risk assessment purposes. Clinical text mining can be used to extract data related to risk factors from unstructured clinical notes. This study presents methods to extract Framingham risk factors from unstructured electronic health records using clinical text mining and to calculate 10-year coronary artery disease risk scores in a cohort of diabetic patients. We developed a rule-based system to extract risk factors: age, gender, total cholesterol, HDL-C, blood pressure, diabetes history and smoking history. The results showed that the output from the text mining system was reliable, but there was a significant amount of missing data to calculate the Framingham risk score. A systematic approach for understanding missing data was followed by implementation of imputation strategies. An analysis of the 10-year Framingham risk scores for coronary artery disease in this cohort has shown that the majority of the diabetic patients are at moderate risk of CAD. Copyright © 2015 Elsevier Inc. All rights reserved.

Simulating hydrodynamics and ice cover in Lake Erie using an unstructured grid model

NASA Astrophysics Data System (ADS)

Fujisaki-Manome, A.; Wang, J.

2016-02-01

An unstructured grid Finite-Volume Coastal Ocean Model (FVCOM) is applied to Lake Erie to simulate seasonal ice cover. The model is coupled with an unstructured-grid, finite-volume version of the Los Alamos Sea Ice Model (UG-CICE). We replaced the original 2-time-step Euler forward scheme in time integration by the central difference (i.e., leapfrog) scheme to assure a neutrally inertial stability. The modified version of FVCOM coupled with the ice model is applied to the shallow freshwater lake in this study using unstructured grids to represent the complicated coastline in the Laurentian Great Lakes and refining the spatial resolution locally. We conducted multi-year simulations in Lake Erie from 2002 to 2013. The results were compared with the observed ice extent, water surface temperature, ice thickness, currents, and water temperature profiles. Seasonal and interannual variation of ice extent and water temperature was captured reasonably, while the modeled thermocline was somewhat diffusive. The modeled ice thickness tends to be systematically thinner than the observed values. The modeled lake currents compared well with measurements obtained from an Acoustic Doppler Current Profiler located in the deep part of the lake, whereas the simulated currents deviated from measurements near the surface, possibly due to the model's inability to reproduce the sharp thermocline during the summer and the lack of detailed representation of offshore wind fields in the interpolated meteorological forcing.

Advanced Computational Aeroacoustics Methods for Fan Noise Prediction

NASA Technical Reports Server (NTRS)

Envia, Edmane (Technical Monitor); Tam, Christopher

2003-01-01

Direct computation of fan noise is presently not possible. One of the major difficulties is the geometrical complexity of the problem. In the case of fan noise, the blade geometry is critical to the loading on the blade and hence the intensity of the radiated noise. The precise geometry must be incorporated into the computation. In computational fluid dynamics (CFD), there are two general ways to handle problems with complex geometry. One way is to use unstructured grids. The other is to use body fitted overset grids. In the overset grid method, accurate data transfer is of utmost importance. For acoustic computation, it is not clear that the currently used data transfer methods are sufficiently accurate as not to contaminate the very small amplitude acoustic disturbances. In CFD, low order schemes are, invariably, used in conjunction with unstructured grids. However, low order schemes are known to be numerically dispersive and dissipative. dissipative errors are extremely undesirable for acoustic wave problems. The objective of this project is to develop a high order unstructured grid Dispersion-Relation-Preserving (DRP) scheme. would minimize numerical dispersion and dissipation errors. contains the results of the funded portion of the project. scheme on an unstructured grid has been developed. constructed in the wave number space. The characteristics of the scheme can be improved by the inclusion of additional constraints. Stability of the scheme has been investigated. Stability can be improved by adopting the upwinding strategy.

Transonic Drag Prediction Using an Unstructured Multigrid Solver

NASA Technical Reports Server (NTRS)

Mavriplis, D. J.; Levy, David W.

2001-01-01

This paper summarizes the results obtained with the NSU-3D unstructured multigrid solver for the AIAA Drag Prediction Workshop held in Anaheim, CA, June 2001. The test case for the workshop consists of a wing-body configuration at transonic flow conditions. Flow analyses for a complete test matrix of lift coefficient values and Mach numbers at a constant Reynolds number are performed, thus producing a set of drag polars and drag rise curves which are compared with experimental data. Results were obtained independently by both authors using an identical baseline grid and different refined grids. Most cases were run in parallel on commodity cluster-type machines while the largest cases were run on an SGI Origin machine using 128 processors. The objective of this paper is to study the accuracy of the subject unstructured grid solver for predicting drag in the transonic cruise regime, to assess the efficiency of the method in terms of convergence, cpu time, and memory, and to determine the effects of grid resolution on this predictive ability and its computational efficiency. A good predictive ability is demonstrated over a wide range of conditions, although accuracy was found to degrade for cases at higher Mach numbers and lift values where increasing amounts of flow separation occur. The ability to rapidly compute large numbers of cases at varying flow conditions using an unstructured solver on inexpensive clusters of commodity computers is also demonstrated.

The Tera Multithreaded Architecture and Unstructured Meshes

NASA Technical Reports Server (NTRS)

Bokhari, Shahid H.; Mavriplis, Dimitri J.

1998-01-01

The Tera Multithreaded Architecture (MTA) is a new parallel supercomputer currently being installed at San Diego Supercomputing Center (SDSC). This machine has an architecture quite different from contemporary parallel machines. The computational processor is a custom design and the machine uses hardware to support very fine grained multithreading. The main memory is shared, hardware randomized and flat. These features make the machine highly suited to the execution of unstructured mesh problems, which are difficult to parallelize on other architectures. We report the results of a study carried out during July-August 1998 to evaluate the execution of EUL3D, a code that solves the Euler equations on an unstructured mesh, on the 2 processor Tera MTA at SDSC. Our investigation shows that parallelization of an unstructured code is extremely easy on the Tera. We were able to get an existing parallel code (designed for a shared memory machine), running on the Tera by changing only the compiler directives. Furthermore, a serial version of this code was compiled to run in parallel on the Tera by judicious use of directives to invoke the "full/empty" tag bits of the machine to obtain synchronization. This version achieves 212 and 406 Mflop/s on one and two processors respectively, and requires no attention to partitioning or placement of data issues that would be of paramount importance in other parallel architectures.

A Proline-Rich N-Terminal Region of the Dengue Virus NS3 Is Crucial for Infectious Particle Production.

PubMed

Gebhard, Leopoldo G; Iglesias, Néstor G; Byk, Laura A; Filomatori, Claudia V; De Maio, Federico A; Gamarnik, Andrea V

2016-06-01

Dengue virus is currently the most important insect-borne viral human pathogen. Viral nonstructural protein 3 (NS3) is a key component of the viral replication machinery that performs multiple functions during viral replication and participates in antiviral evasion. Using dengue virus infectious clones and reporter systems to dissect each step of the viral life cycle, we examined the requirements of different domains of NS3 on viral particle assembly. A thorough site-directed mutagenesis study based on solvent-accessible surface areas of NS3 revealed that, in addition to being essential for RNA replication, different domains of dengue virus NS3 are critically required for production of infectious viral particles. Unexpectedly, point mutations in the protease, interdomain linker, or helicase domain were sufficient to abolish infectious particle formation without affecting translation, polyprotein processing, or RNA replication. In particular, we identified a novel proline-rich N-terminal unstructured region of NS3 that contains several amino acid residues involved in infectious particle formation. We also showed a new role for the interdomain linker of NS3 in virion assembly. In conclusion, we present a comprehensive genetic map of novel NS3 determinants for viral particle assembly. Importantly, our results provide evidence of a central role of NS3 in the coordination of both dengue virus RNA replication and particle formation. Dengue virus is an important human pathogen, and its prominence is expanding globally; however, basic aspects of its biology are still unclear, hindering the development of effective therapeutic and prophylactic treatments. Little is known about the initial steps of dengue and other flavivirus particle assembly. This process involves a complex interplay between viral and cellular components, making it an attractive antiviral target. Unpredictably, we identified spatially separated regions of the large NS3 viral protein as determinants for dengue virus particle assembly. NS3 is a multifunctional enzyme that participates in different steps of the viral life cycle. Using reporter systems to dissect different viral processes, we identified a novel N-terminal unstructured region of the NS3 protein as crucial for production of viral particles. Based on our findings, we propose new ideas that include NS3 as a possible scaffold for the viral assembly process. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

A Sequence-Independent, Unstructured Internal Ribosome Entry Site Is Responsible for Internal Expression of the Coat Protein of Turnip Crinkle Virus

PubMed Central

May, Jared; Johnson, Philip; Saleem, Huma

2017-01-01

ABSTRACT To maximize the coding potential of viral genomes, internal ribosome entry sites (IRES) can be used to bypass the traditional requirement of a 5′ cap and some/all of the associated translation initiation factors. Although viral IRES typically contain higher-order RNA structure, an unstructured sequence of about 84 nucleotides (nt) immediately upstream of the Turnip crinkle virus (TCV) coat protein (CP) open reading frame (ORF) has been found to promote internal expression of the CP from the genomic RNA (gRNA) both in vitro and in vivo. An absence of extensive RNA structure was predicted using RNA folding algorithms and confirmed by selective 2′-hydroxyl acylation analyzed by primer extension (SHAPE) RNA structure probing. Analysis of the IRES region in vitro by use of both the TCV gRNA and reporter constructs did not reveal any sequence-specific elements but rather suggested that an overall lack of structure was an important feature for IRES activity. The CP IRES is A-rich, independent of orientation, and strongly conserved among viruses in the same genus. The IRES was dependent on eIF4G, but not eIF4E, for activity. Low levels of CP accumulated in vivo in the absence of detectable TCV subgenomic RNAs, strongly suggesting that the IRES was active in the gRNA in vivo. Since the TCV CP also serves as the viral silencing suppressor, early translation of the CP from the viral gRNA is likely important for countering host defenses. Cellular mRNA IRES also lack extensive RNA structures or sequence conservation, suggesting that this viral IRES and cellular IRES may have similar strategies for internal translation initiation. IMPORTANCE Cap-independent translation is a common strategy among positive-sense, single-stranded RNA viruses for bypassing the host cell requirement of a 5′ cap structure. Viral IRES, in general, contain extensive secondary structure that is critical for activity. In contrast, we demonstrate that a region of viral RNA devoid of extensive secondary structure has IRES activity and produces low levels of viral coat protein in vitro and in vivo. Our findings may be applicable to cellular mRNA IRES that also have little or no sequences/structures in common. PMID:28179526

Interplay between Chaperones and Protein Disorder Promotes the Evolution of Protein Networks

PubMed Central

Pechmann, Sebastian; Frydman, Judith

2014-01-01

Evolution is driven by mutations, which lead to new protein functions but come at a cost to protein stability. Non-conservative substitutions are of interest in this regard because they may most profoundly affect both function and stability. Accordingly, organisms must balance the benefit of accepting advantageous substitutions with the possible cost of deleterious effects on protein folding and stability. We here examine factors that systematically promote non-conservative mutations at the proteome level. Intrinsically disordered regions in proteins play pivotal roles in protein interactions, but many questions regarding their evolution remain unanswered. Similarly, whether and how molecular chaperones, which have been shown to buffer destabilizing mutations in individual proteins, generally provide robustness during proteome evolution remains unclear. To this end, we introduce an evolutionary parameter λ that directly estimates the rate of non-conservative substitutions. Our analysis of λ in Escherichia coli, Saccharomyces cerevisiae, and Homo sapiens sequences reveals how co- and post-translationally acting chaperones differentially promote non-conservative substitutions in their substrates, likely through buffering of their destabilizing effects. We further find that λ serves well to quantify the evolution of intrinsically disordered proteins even though the unstructured, thus generally variable regions in proteins are often flanked by very conserved sequences. Crucially, we show that both intrinsically disordered proteins and highly re-wired proteins in protein interaction networks, which have evolved new interactions and functions, exhibit a higher λ at the expense of enhanced chaperone assistance. Our findings thus highlight an intricate interplay of molecular chaperones and protein disorder in the evolvability of protein networks. Our results illuminate the role of chaperones in enabling protein evolution, and underline the importance of the cellular context and integrated approaches for understanding proteome evolution. We feel that the development of λ may be a valuable addition to the toolbox applied to understand the molecular basis of evolution. PMID:24968255

Expanding the proteome: disordered and alternatively-folded proteins

PubMed Central

Dyson, H. Jane

2011-01-01

Proteins provide much of the scaffolding for life, as well as undertaking a variety of essential catalytic reactions. These characteristic functions have led us to presuppose that proteins are in general functional only when well-structured and correctly folded. As we begin to explore the repertoire of possible protein sequences inherent in the human and other genomes, two stark facts that belie this supposition become clear: firstly, the number of apparent open reading frames in the human genome is significantly smaller than appears to be necessary to code for all of the diverse proteins in higher organisms, and secondly that a significant proportion of the protein sequences that would be coded by the genome would not be expected to form stable three-dimensional structures. Clearly the genome must include coding for a multitude of alternative forms of proteins, some of which may be partly or fully disordered or incompletely structured in their functional states. At the same time as this likelihood was recognized, experimental studies also began to uncover examples of important protein molecules and domains that were incompletely structured or completely disordered in solution, yet remained perfectly functional. In the ensuing years, we have seen an explosion of experimental and genome-annotation studies that have mapped the extent of the intrinsic disorder phenomenon and explored the possible biological rationales for its widespread occurrence. Answers to the question “why would a particular domain need to be unstructured?” are as varied as the systems where such domains are found. This review provides a survey of recent new directions in this field, and includes an evaluation of the role not only of intrinsically disordered proteins but of partially structured and highly dynamic members of the disorder-order continuum. PMID:21729349

Monoclonal antibodies against pools of mono- and polyacetylated peptides selectively recognize acetylated lysines within the context of the original antigen.

PubMed

Sandomenico, Annamaria; Focà, Annalia; Sanguigno, Luca; Caporale, Andrea; Focà, Giuseppina; Pignalosa, Angelica; Corvino, Giusy; Caragnano, Angela; Beltrami, Antonio Paolo; Antoniali, Giulia; Tell, Gianluca; Leonardi, Antonio; Ruvo, Menotti

Post-translational modifications (PTMs) strongly influence the structure and function of proteins. Lysine side chain acetylation is one of the most widespread PTMs, and it plays a major role in several physiological and pathological mechanisms. Protein acetylation may be detected by mass spectrometry (MS), but the use of monoclonal antibodies (mAbs) is a useful and cheaper option. Here, we explored the feasibility of generating mAbs against single or multiple acetylations within the context of a specific sequence. As a model, we used the unstructured N-terminal domain of APE1, which is acetylated on Lys27, Lys31, Lys32 and Lys35. As immunogen, we used a peptide mixture containing all combinations of single or multi-acetylated variants encompassing the 24-39 protein region. Targeted screening of the resulting clones yielded mAbs that bind with high affinity to only the acetylated APE1 peptides and the acetylated protein. No binding was seen with the non-acetylated variant or unrelated acetylated peptides and proteins, suggesting a high specificity for the APE1 acetylated molecules. MAbs could not finely discriminate between the differently acetylated variants; however, they specifically bound the acetylated protein in mammalian cell extracts and in intact cells and tissue slices from both breast cancers and from a patient affected by idiopathic dilated cardiomyopathy. The data suggest that our approach is a rapid and cost-effective method to generate mAbs against specific proteins modified by multiple acetylations or other PTMs.

Mapping the O-Mannose Glycoproteome in Saccharomyces cerevisiae *

PubMed Central

Neubert, Patrick; Halim, Adnan; Zauser, Martin; Essig, Andreas; Joshi, Hiren J.; Zatorska, Ewa; Larsen, Ida Signe Bohse; Loibl, Martin; Castells-Ballester, Joan; Aebi, Markus; Clausen, Henrik; Strahl, Sabine

2016-01-01

O-Mannosylation is a vital protein modification conserved from fungi to humans. Yeast is a perfect model to study this post-translational modification, because in contrast to mammals O-mannosylation is the only type of O-glycosylation. In an essential step toward the full understanding of protein O-mannosylation we mapped the O-mannose glycoproteome in baker's yeast. Taking advantage of an O-glycan elongation deficient yeast strain to simplify sample complexity, we identified over 500 O-glycoproteins from all subcellular compartments for which over 2300 O-mannosylation sites were mapped by electron-transfer dissociation (ETD)-based MS/MS. In this study, we focus on the 293 O-glycoproteins (over 1900 glycosylation sites identified by ETD-MS/MS) that enter the secretory pathway and are targets of ER-localized protein O-mannosyltransferases. We find that O-mannosylation is not only a prominent modification of cell wall and plasma membrane proteins, but also of a large number of proteins from the secretory pathway with crucial functions in protein glycosylation, folding, quality control, and trafficking. The analysis of glycosylation sites revealed that O-mannosylation is favored in unstructured regions and β-strands. Furthermore, O-mannosylation is impeded in the proximity of N-glycosylation sites suggesting the interplay of these types of post-translational modifications. The detailed knowledge of the target proteins and their O-mannosylation sites opens for discovery of new roles of this essential modification in eukaryotes, and for a first glance on the evolution of different types of O-glycosylation from yeast to mammals. PMID:26764011

Flow simulations about steady-complex and unsteady moving configurations using structured-overlapped and unstructured grids

NASA Technical Reports Server (NTRS)

Newman, James C., III

1995-01-01

The limiting factor in simulating flows past realistic configurations of interest has been the discretization of the physical domain on which the governing equations of fluid flow may be solved. In an attempt to circumvent this problem, many Computational Fluid Dynamic (CFD) methodologies that are based on different grid generation and domain decomposition techniques have been developed. However, due to the costs involved and expertise required, very few comparative studies between these methods have been performed. In the present work, the two CFD methodologies which show the most promise for treating complex three-dimensional configurations as well as unsteady moving boundary problems are evaluated. These are namely the structured-overlapped and the unstructured grid schemes. Both methods use a cell centered, finite volume, upwind approach. The structured-overlapped algorithm uses an approximately factored, alternating direction implicit scheme to perform the time integration, whereas, the unstructured algorithm uses an explicit Runge-Kutta method. To examine the accuracy, efficiency, and limitations of each scheme, they are applied to the same steady complex multicomponent configurations and unsteady moving boundary problems. The steady complex cases consist of computing the subsonic flow about a two-dimensional high-lift multielement airfoil and the transonic flow about a three-dimensional wing/pylon/finned store assembly. The unsteady moving boundary problems are a forced pitching oscillation of an airfoil in a transonic freestream and a two-dimensional, subsonic airfoil/store separation sequence. Accuracy was accessed through the comparison of computed and experimentally measured pressure coefficient data on several of the wing/pylon/finned store assembly's components and at numerous angles-of-attack for the pitching airfoil. From this study, it was found that both the structured-overlapped and the unstructured grid schemes yielded flow solutions of comparable accuracy for these simulations. This study also indicated that, overall, the structured-overlapped scheme was slightly more CPU efficient than the unstructured approach.

MODFLOW–USG version 1: An unstructured grid version of MODFLOW for simulating groundwater flow and tightly coupled processes using a control volume finite-difference formulation

USGS Publications Warehouse

Panday, Sorab; Langevin, Christian D.; Niswonger, Richard G.; Ibaraki, Motomu; Hughes, Joseph D.

2013-01-01

A new version of MODFLOW, called MODFLOW–USG (for UnStructured Grid), was developed to support a wide variety of structured and unstructured grid types, including nested grids and grids based on prismatic triangles, rectangles, hexagons, and other cell shapes. Flexibility in grid design can be used to focus resolution along rivers and around wells, for example, or to subdiscretize individual layers to better represent hydrostratigraphic units. MODFLOW–USG is based on an underlying control volume finite difference (CVFD) formulation in which a cell can be connected to an arbitrary number of adjacent cells. To improve accuracy of the CVFD formulation for irregular grid-cell geometries or nested grids, a generalized Ghost Node Correction (GNC) Package was developed, which uses interpolated heads in the flow calculation between adjacent connected cells. MODFLOW–USG includes a Groundwater Flow (GWF) Process, based on the GWF Process in MODFLOW–2005, as well as a new Connected Linear Network (CLN) Process to simulate the effects of multi-node wells, karst conduits, and tile drains, for example. The CLN Process is tightly coupled with the GWF Process in that the equations from both processes are formulated into one matrix equation and solved simultaneously. This robustness results from using an unstructured grid with unstructured matrix storage and solution schemes. MODFLOW–USG also contains an optional Newton-Raphson formulation, based on the formulation in MODFLOW–NWT, for improving solution convergence and avoiding problems with the drying and rewetting of cells. Because the existing MODFLOW solvers were developed for structured and symmetric matrices, they were replaced with a new Sparse Matrix Solver (SMS) Package developed specifically for MODFLOW–USG. The SMS Package provides several methods for resolving nonlinearities and multiple symmetric and asymmetric linear solution schemes to solve the matrix arising from the flow equations and the Newton-Raphson formulation, respectively.

Computation of UH-60A Airloads Using CFD/CSD Coupling on Unstructured Meshes

NASA Technical Reports Server (NTRS)

Biedron, Robert T.; Lee-Rausch, Elizabeth M.

2011-01-01

An unsteady Reynolds-averaged Navier-Stokes solver for unstructured grids is used to compute the rotor airloads on the UH-60A helicopter at high-speed and high thrust conditions. The flow solver is coupled to a rotorcraft comprehensive code in order to account for trim and aeroelastic deflections. Simulations are performed both with and without the fuselage, and the effects of grid resolution, temporal resolution and turbulence model are examined. Computed airloads are compared to flight data.

Multiple chiral topological states in liquid crystals from unstructured light beams

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

Loussert, Charles; Brasselet, Etienne, E-mail: e.brasselet@loma.u-bordeaux1.fr

2014-02-03

It is shown experimentally that unstructured light beams can generate a wealth of distinct metastable defect structures in thin films of chiral liquid crystals. Various kinds of individual chiral topological states are obtained as well as dimers and trimers, which correspond to the entanglement of several topological unit cells. Self-assembled nested assemblies of several metastable particle-like topological states can also be formed. Finally, we propose and experimentally demonstrate an opto-electrical approach to generate tailor-made architectures.

Exchanging Peers to Establish P2P Networks

NASA Astrophysics Data System (ADS)

Akon, Mursalin; Islam, Mohammad Towhidul; Shen, Xuemin(Sherman); Singh, Ajit

Structure-wise, P2P networks can be divided into two major categories: (1) structured and (2) unstructured. In this chapter, we survey a group of unstructured P2P networks. This group of networks employs a gossip or epidemic protocol to maintain the members of the network and during a gossip, peers exchange a subset of their neighbors with each other. It is reported that this kind of networks are scalable, robust and resilient to severe network failure, at the same time very inexpensive to operate.

Segmentation of Unstructured Datasets

NASA Technical Reports Server (NTRS)

Bhat, Smitha

1996-01-01

Datasets generated by computer simulations and experiments in Computational Fluid Dynamics tend to be extremely large and complex. It is difficult to visualize these datasets using standard techniques like Volume Rendering and Ray Casting. Object Segmentation provides a technique to extract and quantify regions of interest within these massive datasets. This thesis explores basic algorithms to extract coherent amorphous regions from two-dimensional and three-dimensional scalar unstructured grids. The techniques are applied to datasets from Computational Fluid Dynamics and from Finite Element Analysis.

YAP Version 4.0

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

Nelson, Eric M.

2004-05-20

The YAP software library computes (1) electromagnetic modes, (2) electrostatic fields, (3) magnetostatic fields and (4) particle trajectories in 2d and 3d models. The code employs finite element methods on unstructured grids of tetrahedral, hexahedral, prism and pyramid elements, with linear through cubic element shapes and basis functions to provide high accuracy. The novel particle tracker is robust, accurate and efficient, even on unstructured grids with discontinuous fields. This software library is a component of the MICHELLE 3d finite element gun code.

An unstructured shock-fitting solver for hypersonic plasma flows in chemical non-equilibrium

NASA Astrophysics Data System (ADS)

Pepe, R.; Bonfiglioli, A.; D'Angola, A.; Colonna, G.; Paciorri, R.

2015-11-01

A CFD solver, using Residual Distribution Schemes on unstructured grids, has been extended to deal with inviscid chemical non-equilibrium flows. The conservative equations have been coupled with a kinetic model for argon plasma which includes the argon metastable state as independent species, taking into account electron-atom and atom-atom processes. Results in the case of an hypersonic flow around an infinite cylinder, obtained by using both shock-capturing and shock-fitting approaches, show higher accuracy of the shock-fitting approach.

CFD in the 1980's from one point of view

NASA Technical Reports Server (NTRS)

Lomax, Harvard

1991-01-01

The present interpretive treatment of the development history of CFD in the 1980s gives attention to advancements in such algorithmic techniques as flux Jacobian-based upwind differencing, total variation-diminishing and essentially nonoscillatory schemes, multigrid methods, unstructured grids, and nonrectangular structured grids. At the same time, computational turbulence research gave attention to turbulence modeling on the bases of increasingly powerful supercomputers and meticulously constructed databases. The major future developments in CFD will encompass such capabilities as structured and unstructured three-dimensional grids.

Membrane Association of the PTEN Tumor Suppressor: Electrostatic Interaction with Phos-phatidylserine-Containing Bilayers and Regulatory Role of the C-Terminal Tail

PubMed Central

Shenoy, Siddharth S.; Nanda, Hirsh; Lösche, Mathias

2012-01-01

The phosphatidylinositolphosphate phosphatase PTEN is the second most frequently mutated protein in human tumors. Its membrane association, allosteric activation and membrane dissociation are poorly understood. We recently reported PTEN binding affinities to membranes of different compositions and a preliminary investigation of the protein-membrane complex with neutron reflectometry (NR). Here we use NR to validate molecular dynamics (MD) simulations of the protein and study conformational differences of the protein in solution and on anionic membranes. NR shows that full-length PTEN binds to such membranes roughly in the conformation and orientation suggested by the crystal structure of a truncated PTEN protein, in contrast with a recently presented model which suggested that membrane binding depends critically on the SUMOylation of the CBR3 loop of PTEN’s C2 domain. Our MD simulations confirm that PTEN is peripherally bound to the bilayer surface and show slight differences of the protein structure in solution and in the membrane-bound state, where the protein body flattens against the bilayer surface. PTEN’s C2 domain binds phosphatidylserine (PS) tightly through its CBR3 loop, and its phosphatase domain also forms electrostatic interactions with PS. NR and MD results show consistently that PTEN’s unstructured, anionic C-terminal tail is repelled from the bilayer surface. In contrast, this tail is tightly tugged against the C2 domain in solution, partially obstructing the membrane-binding interface of the protein. Arresting the C-terminal tail in this conformation by phosphorylation may provide a control mechanism for PTEN’s membrane binding and activity. PMID:23073177

Membrane association of the PTEN tumor suppressor: electrostatic interaction with phosphatidylserine-containing bilayers and regulatory role of the C-terminal tail.

PubMed

Shenoy, Siddharth S; Nanda, Hirsh; Lösche, Mathias

2012-12-01

The phosphatidylinositolphosphate phosphatase PTEN is the second most frequently mutated protein in human tumors. Its membrane association, allosteric activation and membrane dissociation are poorly understood. We recently reported PTEN binding affinities to membranes of different compositions (Shenoy et al., 2012, PLoS ONE 7, e32591) and a preliminary investigation of the protein-membrane complex with neutron reflectometry (NR). Here we use NR to validate molecular dynamics (MD) simulations of the protein and study conformational differences of the protein in solution and on anionic membranes. NR shows that full-length PTEN binds to such membranes roughly in the conformation and orientation suggested by the crystal structure of a truncated PTEN protein, in contrast with a recently presented model which suggested that membrane binding depends critically on the SUMOylation of the CBR3 loop of PTEN's C2 domain. Our MD simulations confirm that PTEN is peripherally bound to the bilayer surface and show slight differences of the protein structure in solution and in the membrane-bound state, where the protein body flattens against the bilayer surface. PTEN's C2 domain binds phosphatidylserine (PS) tightly through its CBR3 loop, and its phosphatase domain also forms electrostatic interactions with PS. NR and MD results show consistently that PTEN's unstructured, anionic C-terminal tail is repelled from the bilayer surface. In contrast, this tail is tightly tugged against the C2 domain in solution, partially obstructing the membrane-binding interface of the protein. Arresting the C-terminal tail in this conformation by phosphorylation may provide a control mechanism for PTEN's membrane binding and activity. Copyright © 2012 Elsevier Inc. All rights reserved.

A Force-Sensing System on Legs for Biomimetic Hexapod Robots Interacting with Unstructured Terrain

PubMed Central

Wu, Rui; Li, Changle; Zang, Xizhe; Zhang, Xuehe; Jin, Hongzhe; Zhao, Jie

2017-01-01

The tiger beetle can maintain its stability by controlling the interaction force between its legs and an unstructured terrain while it runs. The biomimetic hexapod robot mimics a tiger beetle, and a comprehensive force sensing system combined with certain algorithms can provide force information that can help the robot understand the unstructured terrain that it interacts with. This study introduces a complicated leg force sensing system for a hexapod robot that is the same for all six legs. First, the layout and configuration of sensing system are designed according to the structure and sizes of legs. Second, the joint toque sensors, 3-DOF foot-end force sensor and force information processing module are designed, and the force sensor performance parameters are tested by simulations and experiments. Moreover, a force sensing system is implemented within the robot control architecture. Finally, the experimental evaluation of the leg force sensor system on the hexapod robot is discussed and the performance of the leg force sensor system is verified. PMID:28654003

Formation flight and collision avoidance for multiple UAVs based on modified tentacle algorithm in unstructured environments

PubMed Central

2017-01-01

This paper presents a method for formation flight and collision avoidance of multiple UAVs. Due to the shortcomings such as collision avoidance caused by UAV’s high-speed and unstructured environments, this paper proposes a modified tentacle algorithm to ensure the high performance of collision avoidance. Different from the conventional tentacle algorithm which uses inverse derivation, the modified tentacle algorithm rapidly matches the radius of each tentacle and the steering command, ensuring that the data calculation problem in the conventional tentacle algorithm is solved. Meanwhile, both the speed sets and tentacles in one speed set are reduced and reconstructed so as to be applied to multiple UAVs. Instead of path iterative optimization, the paper selects the best tentacle to obtain the UAV collision avoidance path quickly. The simulation results show that the method presented in the paper effectively enhances the performance of flight formation and collision avoidance for multiple high-speed UAVs in unstructured environments. PMID:28763498

Personalized Guideline-Based Treatment Recommendations Using Natural Language Processing Techniques.

PubMed

Becker, Matthias; Böckmann, Britta

2017-01-01

Clinical guidelines and clinical pathways are accepted and proven instruments for quality assurance and process optimization. Today, electronic representation of clinical guidelines exists as unstructured text, but is not well-integrated with patient-specific information from electronic health records. Consequently, generic content of the clinical guidelines is accessible, but it is not possible to visualize the position of the patient on the clinical pathway, decision support cannot be provided by personalized guidelines for the next treatment step. The Systematized Nomenclature of Medicine - Clinical Terms (SNOMED CT) provides common reference terminology as well as the semantic link for combining the pathways and the patient-specific information. This paper proposes a model-based approach to support the development of guideline-compliant pathways combined with patient-specific structured and unstructured information using SNOMED CT. To identify SNOMED CT concepts, a software was developed to extract SNOMED CT codes out of structured and unstructured German data to map these with clinical pathways annotated in accordance with the systematized nomenclature.

Efficient Parallelization of a Dynamic Unstructured Application on the Tera MTA

NASA Technical Reports Server (NTRS)

Oliker, Leonid; Biswas, Rupak

1999-01-01

The success of parallel computing in solving real-life computationally-intensive problems relies on their efficient mapping and execution on large-scale multiprocessor architectures. Many important applications are both unstructured and dynamic in nature, making their efficient parallel implementation a daunting task. This paper presents the parallelization of a dynamic unstructured mesh adaptation algorithm using three popular programming paradigms on three leading supercomputers. We examine an MPI message-passing implementation on the Cray T3E and the SGI Origin2OOO, a shared-memory implementation using cache coherent nonuniform memory access (CC-NUMA) of the Origin2OOO, and a multi-threaded version on the newly-released Tera Multi-threaded Architecture (MTA). We compare several critical factors of this parallel code development, including runtime, scalability, programmability, and memory overhead. Our overall results demonstrate that multi-threaded systems offer tremendous potential for quickly and efficiently solving some of the most challenging real-life problems on parallel computers.

Jali - Unstructured Mesh Infrastructure for Multi-Physics Applications

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

Garimella, Rao V; Berndt, Markus; Coon, Ethan

2017-04-13

Jali is a parallel unstructured mesh infrastructure library designed for use by multi-physics simulations. It supports 2D and 3D arbitrary polyhedral meshes distributed over hundreds to thousands of nodes. Jali can read write Exodus II meshes along with fields and sets on the mesh and support for other formats is partially implemented or is (https://github.com/MeshToolkit/MSTK), an open source general purpose unstructured mesh infrastructure library from Los Alamos National Laboratory. While it has been made to work with other mesh frameworks such as MOAB and STKmesh in the past, support for maintaining the interface to these frameworks has been suspended formore » now. Jali supports distributed as well as on-node parallelism. Support of on-node parallelism is through direct use of the the mesh in multi-threaded constructs or through the use of "tiles" which are submeshes or sub-partitions of a partition destined for a compute node.« less

A package for 3-D unstructured grid generation, finite-element flow solution and flow field visualization

NASA Technical Reports Server (NTRS)

Parikh, Paresh; Pirzadeh, Shahyar; Loehner, Rainald

1990-01-01

A set of computer programs for 3-D unstructured grid generation, fluid flow calculations, and flow field visualization was developed. The grid generation program, called VGRID3D, generates grids over complex configurations using the advancing front method. In this method, the point and element generation is accomplished simultaneously, VPLOT3D is an interactive, menudriven pre- and post-processor graphics program for interpolation and display of unstructured grid data. The flow solver, VFLOW3D, is an Euler equation solver based on an explicit, two-step, Taylor-Galerkin algorithm which uses the Flux Corrected Transport (FCT) concept for a wriggle-free solution. Using these programs, increasingly complex 3-D configurations of interest to aerospace community were gridded including a complete Space Transportation System comprised of the space-shuttle orbitor, the solid-rocket boosters, and the external tank. Flow solutions were obtained on various configurations in subsonic, transonic, and supersonic flow regimes.

On the application of Chimera/unstructured hybrid grids for conjugate heat transfer

NASA Technical Reports Server (NTRS)

Kao, Kai-Hsiung; Liou, Meng-Sing

1995-01-01

A hybrid grid system that combines the Chimera overset grid scheme and an unstructured grid method is developed to study fluid flow and heat transfer problems. With the proposed method, the solid structural region, in which only the heat conduction is considered, can be easily represented using an unstructured grid method. As for the fluid flow region external to the solid material, the Chimera overset grid scheme has been shown to be very flexible and efficient in resolving complex configurations. The numerical analyses require the flow field solution and material thermal response to be obtained simultaneously. A continuous transfer of temperature and heat flux is specified at the interface, which connects the solid structure and the fluid flow as an integral system. Numerical results are compared with analytical and experimental data for a flat plate and a C3X cooled turbine cascade. A simplified drum-disk system is also simulated to show the effectiveness of this hybrid grid system.

Revisiting the Least-squares Procedure for Gradient Reconstruction on Unstructured Meshes

NASA Technical Reports Server (NTRS)

Mavriplis, Dimitri J.; Thomas, James L. (Technical Monitor)

2003-01-01

The accuracy of the least-squares technique for gradient reconstruction on unstructured meshes is examined. While least-squares techniques produce accurate results on arbitrary isotropic unstructured meshes, serious difficulties exist for highly stretched meshes in the presence of surface curvature. In these situations, gradients are typically under-estimated by up to an order of magnitude. For vertex-based discretizations on triangular and quadrilateral meshes, and cell-centered discretizations on quadrilateral meshes, accuracy can be recovered using an inverse distance weighting in the least-squares construction. For cell-centered discretizations on triangles, both the unweighted and weighted least-squares constructions fail to provide suitable gradient estimates for highly stretched curved meshes. Good overall flow solution accuracy can be retained in spite of poor gradient estimates, due to the presence of flow alignment in exactly the same regions where the poor gradient accuracy is observed. However, the use of entropy fixes has the potential for generating large but subtle discretization errors.

Runge-Kutta discontinuous Galerkin method using a new type of WENO limiters on unstructured meshes

NASA Astrophysics Data System (ADS)

Zhu, Jun; Zhong, Xinghui; Shu, Chi-Wang; Qiu, Jianxian

2013-09-01

In this paper we generalize a new type of limiters based on the weighted essentially non-oscillatory (WENO) finite volume methodology for the Runge-Kutta discontinuous Galerkin (RKDG) methods solving nonlinear hyperbolic conservation laws, which were recently developed in [32] for structured meshes, to two-dimensional unstructured triangular meshes. The key idea of such limiters is to use the entire polynomials of the DG solutions from the troubled cell and its immediate neighboring cells, and then apply the classical WENO procedure to form a convex combination of these polynomials based on smoothness indicators and nonlinear weights, with suitable adjustments to guarantee conservation. The main advantage of this new limiter is its simplicity in implementation, especially for the unstructured meshes considered in this paper, as only information from immediate neighbors is needed and the usage of complicated geometric information of the meshes is largely avoided. Numerical results for both scalar equations and Euler systems of compressible gas dynamics are provided to illustrate the good performance of this procedure.

Unstructured Grids for Sonic Boom Analysis and Design

NASA Technical Reports Server (NTRS)

Campbell, Richard L.; Nayani, Sudheer N.

2015-01-01

An evaluation of two methods for improving the process for generating unstructured CFD grids for sonic boom analysis and design has been conducted. The process involves two steps: the generation of an inner core grid using a conventional unstructured grid generator such as VGRID, followed by the extrusion of a sheared and stretched collar grid through the outer boundary of the core grid. The first method evaluated, known as COB, automatically creates a cylindrical outer boundary definition for use in VGRID that makes the extrusion process more robust. The second method, BG, generates the collar grid by extrusion in a very efficient manner. Parametric studies have been carried out and new options evaluated for each of these codes with the goal of establishing guidelines for best practices for maintaining boom signature accuracy with as small a grid as possible. In addition, a preliminary investigation examining the use of the CDISC design method for reducing sonic boom utilizing these grids was conducted, with initial results confirming the feasibility of a new remote design approach.

The clinical performance of the M4 decision support model to triage women with a pregnancy of unknown location as at low or high risk of complications

PubMed Central

Bobdiwala, S.; Guha, S.; Van Calster, B.; Ayim, F.; Mitchell-Jones, N.; Al-Memar, M.; Mitchell, H.; Stalder, C.; Bottomley, C.; Kothari, A.; Timmerman, D.; Bourne, T.

2016-01-01

STUDY QUESTION What are the adverse outcomes associated with using the M4 model in everyday clinical practice for women with pregnancy of unknown location (PUL)? SUMMARY ANSWER There were 17/835 (2.0%) adverse events and no serious adverse events associated with the performance of the M4 model in clinical practice. WHAT IS KNOWN ALREADY The M4 model has previously been shown to stratify women classified as a PUL as at low or high risk of complications with a good level of test performance. The triage performance of the M4 model is better than single measurements of serum progesterone or the hCG ratio (serum hCG at 48 h/hCG at presentation). STUDY DESIGN, SIZE, DURATION A prospective multi-centre cohort study of 1022 women with a PUL carried out between August 2012 and December 2013 across 2 university teaching hospitals and 1 district general hospital. PARTICIPANTS/MATERIALS, SETTING, METHODS All women presenting with a PUL to the early pregnancy units of the three hospitals were recruited. The final outcome for PUL was either a failed PUL (FPUL), intrauterine pregnancy (IUP) or ectopic pregnancy (EP) (including persistent PUL (PPUL)), with EP and PPUL considered high-risk PUL. Their hCG results at 0 and 48 h were entered into the M4 model algorithm. If the risk of EP was ≥5%, the PUL was predicted to be high-risk and the participant was asked to re-attend 48 h later for a repeat hCG and transvaginal ultrasound scan by a senior clinician. If the PUL was classified as ‘low risk, likely failed PUL’, the participant was asked to perform a urinary pregnancy test 2 weeks later. If the PUL was classified as ‘low risk, likely intrauterine’, the participant was scheduled for a repeat scan in 1 week. Deviations from the management protocol were recorded as either an ‘unscheduled visit (participant reason)’, ‘unscheduled visit (clinician reason)’ or ‘differences in timing (blood test/ultrasound)’. Adverse events were assessed using definitions outlined in the UK Good Clinical Practice Guidelines' document. MAIN RESULTS AND THE ROLE OF CHANCE A total of 835 (82%) women classified as a PUL were managed according to the M4 model (9 met the exclusion criteria, 69 were lost to follow-up, 109 had no hCG result at 48 h). Of these, 443 (53%) had a final outcome of FPUL, 298 (36%) an IUP and 94 (11%) an EP. The M4 model predicted 70% (585/835) PUL as low risk, of which 568 (97%) were confirmed as FPUL or IUP. Of the 17 EP and PPUL misclassified as low risk, 5 had expectant management, 7 medical management with methotrexate and 5 surgical intervention. Nineteen PUL had an unscheduled visit (participant reason), 38 PUL had an unscheduled visit (clinician reason) and 68 PUL had deviations from protocol due to a difference in timing (blood test/ultrasound). Adverse events were reported in 26 PUL and 1 participant had a serious adverse event. A total of 17/26 (65%) adverse events were misclassifications of a high risk PUL as low risk by the M4 model, while 5/26 (19%) adverse events were related to incorrect clinical decisions. Four of the 26 adverse events (15%) were secondary to unscheduled admissions for pain/bleeding. The serious adverse event was due to an incorrect clinical decision. LIMITATIONS, REASONS FOR CAUTION A limitation of the study was that 69/1022 (7%) of PUL were lost to follow-up. A 48 h hCG level was missing for 109/1022 (11%) participants. WIDER IMPLICATIONS OF THE FINDINGS The low number of adverse events (2.0%) suggests that expectant management of PUL using the M4 prediction model is safe. The model is an effective way of triaging women with a PUL as being at high- and low-risk of complications and rationalizing follow-up. The multi-centre design of the study is more likely to make the performance of the M4 model generalizable in other populations. STUDY FUNDING/COMPETING INTEREST(S) None. TRIAL REGISTRATION NUMBER Not applicable. PMID:27165655

The length but not the sequence of peptide linker modules exerts the primary influence on the conformations of protein domains in cellulosome multi-enzyme complexes.

PubMed

Różycki, Bartosz; Cazade, Pierre-André; O'Mahony, Shane; Thompson, Damien; Cieplak, Marek

2017-08-16

Cellulosomes are large multi-protein catalysts produced by various anaerobic microorganisms to efficiently degrade plant cell-wall polysaccharides down into simple sugars. X-ray and physicochemical structural characterisations show that cellulosomes are composed of numerous protein domains that are connected by unstructured polypeptide segments, yet the properties and possible roles of these 'linker' peptides are largely unknown. We have performed coarse-grained and all-atom molecular dynamics computer simulations of a number of cellulosomal linkers of different lengths and compositions. Our data demonstrates that the effective stiffness of the linker peptides, as quantified by the equilibrium fluctuations in the end-to-end distances, depends primarily on the length of the linker and less so on the specific amino acid sequence. The presence of excluded volume - provided by the domains that are connected - dampens the motion of the linker residues and reduces the effective stiffness of the linkers. Simultaneously, the presence of the linkers alters the conformations of the protein domains that are connected. We demonstrate that short, stiff linkers induce significant rearrangements in the folded domains of the mini-cellulosome composed of endoglucanase Cel8A in complex with scaffoldin ScafT (Cel8A-ScafT) of Clostridium thermocellum as well as in a two-cohesin system derived from the scaffoldin ScaB of Acetivibrio cellulolyticus. We give experimentally testable predictions on structural changes in protein domains that depend on the length of linkers.

Scalable hierarchical PDE sampler for generating spatially correlated random fields using nonmatching meshes: Scalable hierarchical PDE sampler using nonmatching meshes

DOE PAGES

Osborn, Sarah; Zulian, Patrick; Benson, Thomas; ...

2018-01-30

This work describes a domain embedding technique between two nonmatching meshes used for generating realizations of spatially correlated random fields with applications to large-scale sampling-based uncertainty quantification. The goal is to apply the multilevel Monte Carlo (MLMC) method for the quantification of output uncertainties of PDEs with random input coefficients on general and unstructured computational domains. We propose a highly scalable, hierarchical sampling method to generate realizations of a Gaussian random field on a given unstructured mesh by solving a reaction–diffusion PDE with a stochastic right-hand side. The stochastic PDE is discretized using the mixed finite element method on anmore » embedded domain with a structured mesh, and then, the solution is projected onto the unstructured mesh. This work describes implementation details on how to efficiently transfer data from the structured and unstructured meshes at coarse levels, assuming that this can be done efficiently on the finest level. We investigate the efficiency and parallel scalability of the technique for the scalable generation of Gaussian random fields in three dimensions. An application of the MLMC method is presented for quantifying uncertainties of subsurface flow problems. Here, we demonstrate the scalability of the sampling method with nonmatching mesh embedding, coupled with a parallel forward model problem solver, for large-scale 3D MLMC simulations with up to 1.9·109 unknowns.« less

Wave Resource Characterization Using an Unstructured Grid Modeling Approach

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

Wu, Wei-Cheng; Yang, Zhaoqing; Wang, Taiping

This paper presents a modeling study conducted on the central Oregon coast for wave resource characterization using the unstructured-grid SWAN model coupled with a nested-grid WWIII model. The flexibility of models of various spatial resolutions and the effects of open- boundary conditions simulated by a nested-grid WWIII model with different physics packages were evaluated. The model results demonstrate the advantage of the unstructured-grid modeling approach for flexible model resolution and good model skills in simulating the six wave resource parameters recommended by the International Electrotechnical Commission in comparison to the observed data in Year 2009 at National Data Buoy Centermore » Buoy 46050. Notably, spectral analysis indicates that the ST4 physics package improves upon the model skill of the ST2 physics package for predicting wave power density for large waves, which is important for wave resource assessment, device load calculation, and risk management. In addition, bivariate distributions show the simulated sea state of maximum occurrence with the ST4 physics package matched the observed data better than that with the ST2 physics package. This study demonstrated that the unstructured-grid wave modeling approach, driven by the nested-grid regional WWIII outputs with the ST4 physics package, can efficiently provide accurate wave hindcasts to support wave resource characterization. Our study also suggests that wind effects need to be considered if the dimension of the model domain is greater than approximately 100 km, or O (10^2 km).« less

Scalable hierarchical PDE sampler for generating spatially correlated random fields using nonmatching meshes: Scalable hierarchical PDE sampler using nonmatching meshes

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

Osborn, Sarah; Zulian, Patrick; Benson, Thomas

This work describes a domain embedding technique between two nonmatching meshes used for generating realizations of spatially correlated random fields with applications to large-scale sampling-based uncertainty quantification. The goal is to apply the multilevel Monte Carlo (MLMC) method for the quantification of output uncertainties of PDEs with random input coefficients on general and unstructured computational domains. We propose a highly scalable, hierarchical sampling method to generate realizations of a Gaussian random field on a given unstructured mesh by solving a reaction–diffusion PDE with a stochastic right-hand side. The stochastic PDE is discretized using the mixed finite element method on anmore » embedded domain with a structured mesh, and then, the solution is projected onto the unstructured mesh. This work describes implementation details on how to efficiently transfer data from the structured and unstructured meshes at coarse levels, assuming that this can be done efficiently on the finest level. We investigate the efficiency and parallel scalability of the technique for the scalable generation of Gaussian random fields in three dimensions. An application of the MLMC method is presented for quantifying uncertainties of subsurface flow problems. Here, we demonstrate the scalability of the sampling method with nonmatching mesh embedding, coupled with a parallel forward model problem solver, for large-scale 3D MLMC simulations with up to 1.9·109 unknowns.« less

Sensation Seeking and Adolescent Alcohol Use: Exploring the Mediating Role of Unstructured Socializing With Peers.

PubMed

Sznitman, Sharon; Engel-Yeger, Batya

2017-05-01

Researchers have theorized that adolescents high in sensation seeking are particularly sensitive to positive reinforcement and the rewarding outcomes of alcohol use, and thus that the personality vulnerability is a direct causal risk factor for alcohol use. In contrast, the routine activity perspective theorizes that part of the effect of sensation seeking on alcohol use goes through the propensity that sensation seekers have towards unstructured socializing with peers. The study tests a model with indirect and direct paths from sensation seeking and participation in unstructured peer socialization to adolescent alcohol use. Cross-sectional data were collected from 360 students in a state-secular Jewish high school (10th to 12th grade) in the center region of Israel. The sample was equally divided between boys (51.9%) and girls (48.1%), respondents' age ranged from 15 to 17 years (mean = 16.02 ± 0.85). Structural equation modeling was used to test the direct and indirect paths. While sensation seeking had a significant direct path to adolescent alcohol use, part of the association was mediated by unstructured socializing with peers. The mediated paths were similar for boys and girls alike. Sensation seeking is primarily biologically determined and prevention efforts are unlikely to modify this personality vulnerability. The results of this study suggest that a promising prevention avenue is to modify extracurricular participation patterns of vulnerable adolescents. © The Author 2017. Medical Council on Alcohol and Oxford University Press. All rights reserved.

A Deep Penetration Problem Calculation Using AETIUS:An Easy Modeling Discrete Ordinates Transport Code UsIng Unstructured Tetrahedral Mesh, Shared Memory Parallel

NASA Astrophysics Data System (ADS)

KIM, Jong Woon; LEE, Young-Ouk

2017-09-01

As computing power gets better and better, computer codes that use a deterministic method seem to be less useful than those using the Monte Carlo method. In addition, users do not like to think about space, angles, and energy discretization for deterministic codes. However, a deterministic method is still powerful in that we can obtain a solution of the flux throughout the problem, particularly as when particles can barely penetrate, such as in a deep penetration problem with small detection volumes. Recently, a new state-of-the-art discrete-ordinates code, ATTILA, was developed and has been widely used in several applications. ATTILA provides the capabilities to solve geometrically complex 3-D transport problems by using an unstructured tetrahedral mesh. Since 2009, we have been developing our own code by benchmarking ATTILA. AETIUS is a discrete ordinates code that uses an unstructured tetrahedral mesh such as ATTILA. For pre- and post- processing, Gmsh is used to generate an unstructured tetrahedral mesh by importing a CAD file (*.step) and visualizing the calculation results of AETIUS. Using a CAD tool, the geometry can be modeled very easily. In this paper, we describe a brief overview of AETIUS and provide numerical results from both AETIUS and a Monte Carlo code, MCNP5, in a deep penetration problem with small detection volumes. The results demonstrate the effectiveness and efficiency of AETIUS for such calculations.

The Fanconi anemia associated protein FAAP24 uses two substrate specific binding surfaces for DNA recognition

PubMed Central

Wienk, Hans; Slootweg, Jack C.; Speerstra, Sietske; Kaptein, Robert; Boelens, Rolf; Folkers, Gert E.

2013-01-01

To maintain the integrity of the genome, multiple DNA repair systems exist to repair damaged DNA. Recognition of altered DNA, including bulky adducts, pyrimidine dimers and interstrand crosslinks (ICL), partially depends on proteins containing helix-hairpin-helix (HhH) domains. To understand how ICL is specifically recognized by the Fanconi anemia proteins FANCM and FAAP24, we determined the structure of the HhH domain of FAAP24. Although it resembles other HhH domains, the FAAP24 domain contains a canonical hairpin motif followed by distorted motif. The HhH domain can bind various DNA substrates; using nuclear magnetic resonance titration experiments, we demonstrate that the canonical HhH motif is required for double-stranded DNA (dsDNA) binding, whereas the unstructured N-terminus can interact with single-stranded DNA. Both DNA binding surfaces are used for binding to ICL-like single/double-strand junction-containing DNA substrates. A structural model for FAAP24 bound to dsDNA has been made based on homology with the translesion polymerase iota. Site-directed mutagenesis, sequence conservation and charge distribution support the dsDNA-binding model. Analogous to other HhH domain-containing proteins, we suggest that multiple FAAP24 regions together contribute to binding to single/double-strand junction, which could contribute to specificity in ICL DNA recognition. PMID:23661679

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

Sharma, Manisha; Jamieson, Cara; Lui, Christina

β-catenin is a key mediator of Wnt signaling and its deregulated nuclear accumulation can drive cancer progression. While the central armadillo (Arm) repeats of β-catenin stimulate nuclear entry, the N- and C-terminal “tail” sequences are thought to regulate turnover and transactivation. We show here that the N- and C-tails are also potent transport sequences. The unstructured tails of β-catenin, when individually fused to a GFP-reporter, could enter and exit the nucleus rapidly in live cells. Proximity ligation assays and pull-down assays identified a weak interaction between the tail sequences and the FG-repeats of nucleoporins, consistent with a possible direct translocationmore » of β-catenin through the nuclear pore complex. Extensive alanine mutagenesis of the tail sequences revealed that nuclear translocation of β-catenin was dependent on specific uniformly distributed patches of hydrophobic residues, whereas the mutagenesis of acidic amino acids had no effect. Moreover, the mutation of hydrophobic patches within the N-tail and C-tail of full length β-catenin reduced nuclear transport rate and diminished its ability to activate transcription. We propose that the tail sequences can contribute to β-catenin transport and suggest a possible similar role for hydrophobic unstructured regions in other proteins. - Highlights: • We show that the N- and C-tails of beta-catenin possess nuclear transport activity. • Nuclear transport of the N- or C-tails requires specific hydrophobic amino acids. • Mutagenesis of the N-terminus diminished nuclear entry of full-length beta-catenin. • We propose the N-tail contributes to beta-catenin nuclear entry and transactivation.« less

Abundance of intrinsic structural disorder in the histone H1 subtypes.

PubMed

Kowalski, Andrzej

2015-12-01

The intrinsically disordered proteins consist of partially structured regions linked to the unstructured stretches, which consequently form the transient and dynamic conformational ensembles. They undergo disorder to order transition upon binding their partners. Intrinsic disorder is attributed to histones H1, perceived as assemblers of chromatin structure and the regulators of DNA and proteins activity. In this work, the comparison of intrinsic disorder abundance in the histone H1 subtypes was performed both by the analysis of their amino acid composition and by the prediction of disordered stretches, as well as by identifying molecular recognition features (MoRFs) and ANCHOR protein binding regions (APBR) that are responsible for recognition and binding. Both human and model organisms-animals, plants, fungi and protists-have H1 histone subtypes with the properties typical of disordered state. They possess a significantly higher content of hydrophilic and charged amino acid residues, arranged in the long regions, covering over half of the whole amino acid residues in chain. Almost complete disorder corresponds to histone H1 terminal domains, including MoRFs and ANCHOR. Those motifs were also identified in a more ordered histone H1 globular domain. Compared to the control (globular and fibrous) proteins, H1 histones demonstrate the increased folding rate and a higher proportion of low-complexity segments. The results of this work indicate that intrinsic disorder is an inherent structural property of histone H1 subtypes and it is essential for establishing a protein conformation which defines functional outcomes affecting on DNA- and/or partner protein-dependent cell processes. Copyright © 2015 Elsevier Ltd. All rights reserved.

The role of proteosome-mediated proteolysis in modulating potentially harmful transcription factor activity in Saccharomyces cerevisiae

PubMed Central

Bonzanni, Nicola; Zhang, Nianshu; Oliver, Stephen G.; Fisher, Jasmin

2011-01-01

Motivation: The appropriate modulation of the stress response to variable environmental conditions is necessary to maintain sustained viability in Saccharomyces cerevisiae. Particularly, controlling the abundance of proteins that may have detrimental effects on cell growth is crucial for rapid recovery from stress-induced quiescence. Results: Prompted by qualitative modeling of the nutrient starvation response in yeast, we investigated in vivo the effect of proteolysis after nutrient starvation showing that, for the Gis1 transcription factor at least, proteasome-mediated control is crucial for a rapid return to growth. Additional bioinformatics analyses show that potentially toxic transcriptional regulators have a significantly lower protein half-life, a higher fraction of unstructured regions and more potential PEST motifs than the non-detrimental ones. Furthermore, inhibiting proteasome activity tends to increase the expression of genes induced during the Environmental Stress Response more than those in the rest of the genome. Our combined results suggest that proteasome-mediated proteolysis of potentially toxic transcription factors tightly modulates the stress response in yeast. Contact: jasmin.fisher@microsoft.com Supplementary information: Supplementary data are available at Bioinformatics online. PMID:21685082

Preprotein mature domains contain translocase targeting signals that are essential for secretion

PubMed Central

Tsirigotaki, Alexandra; Koukaki, Marina; Šoštarić, Nikolina; Konijnenberg, Albert; Sobott, Frank; Kalodimos, Charalampos G.; Karamanou, Spyridoula

2017-01-01

Secretory proteins are only temporary cytoplasmic residents. They are typically synthesized as preproteins, carrying signal peptides N-terminally fused to their mature domains. In bacteria secretion largely occurs posttranslationally through the membrane-embedded SecA-SecYEG translocase. Upon crossing the plasma membrane, signal peptides are cleaved off and mature domains reach their destinations and fold. Targeting to the translocase is mediated by signal peptides. The role of mature domains in targeting and secretion is unclear. We now reveal that mature domains harbor their own independent targeting signals (mature domain targeting signals [MTSs]). These are multiple, degenerate, interchangeable, linear or 3D hydrophobic stretches that become available because of the unstructured states of targeting-competent preproteins. Their receptor site on the cytoplasmic face of the SecYEG-bound SecA is also of hydrophobic nature and is located adjacent to the signal peptide cleft. Both the preprotein MTSs and their receptor site on SecA are essential for protein secretion. Evidently, mature domains have their own previously unsuspected distinct roles in preprotein targeting and secretion. PMID:28404644

Crystal structure of the human heterogeneous ribonucleoprotein A18 RNA-recognition motif

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

Coburn, Katherine; Melville, Zephan; Aligholizadeh, Ehson

The heterogeneous ribonucleoprotein A18 (hnRNP A18) is upregulated in hypoxic regions of various solid tumors and promotes tumor growthviathe coordination of mRNA transcripts associated with pro-survival genes. Thus, hnRNP A18 represents an important therapeutic target in tumor cells. Presented here is the first X-ray crystal structure to be reported for the RNA-recognition motif of hnRNP A18. By comparing this structure with those of homologous RNA-binding proteins (i.e.hnRNP A1), three residues on one face of an antiparallel β-sheet (Arg48, Phe50 and Phe52) and one residue in an unstructured loop (Arg41) were identified as likely to be involved in protein–nucleic acid interactions.more » This structure helps to serve as a foundation for biophysical studies of this RNA-binding protein and structure-based drug-design efforts for targeting hnRNP A18 in cancer, such as malignant melanoma, where hnRNP A18 levels are elevated and contribute to disease progression.« less

Submillisecond elastic recoil reveals molecular origins of fibrin fiber mechanics.

PubMed

Hudson, Nathan E; Ding, Feng; Bucay, Igal; O'Brien, E Timothy; Gorkun, Oleg V; Superfine, Richard; Lord, Susan T; Dokholyan, Nikolay V; Falvo, Michael R

2013-06-18

Fibrin fibers form the structural scaffold of blood clots. Thus, their mechanical properties are of central importance to understanding hemostasis and thrombotic disease. Recent studies have revealed that fibrin fibers are elastomeric despite their high degree of molecular ordering. These results have inspired a variety of molecular models for fibrin's elasticity, ranging from reversible protein unfolding to rubber-like elasticity. An important property that has not been explored is the timescale of elastic recoil, a parameter that is critical for fibrin's mechanical function and places a temporal constraint on molecular models of fiber elasticity. Using high-frame-rate imaging and atomic force microscopy-based nanomanipulation, we measured the recoil dynamics of individual fibrin fibers and found that the recoil was orders of magnitude faster than anticipated from models involving protein refolding. We also performed steered discrete molecular-dynamics simulations to investigate the molecular origins of the observed recoil. Our results point to the unstructured αC regions of the otherwise structured fibrin molecule as being responsible for the elastic recoil of the fibers. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Submillisecond Elastic Recoil Reveals Molecular Origins of Fibrin Fiber Mechanics

PubMed Central

Hudson, Nathan E.; Ding, Feng; Bucay, Igal; O’Brien, E. Timothy; Gorkun, Oleg V.; Superfine, Richard; Lord, Susan T.; Dokholyan, Nikolay V.; Falvo, Michael R.

2013-01-01

Fibrin fibers form the structural scaffold of blood clots. Thus, their mechanical properties are of central importance to understanding hemostasis and thrombotic disease. Recent studies have revealed that fibrin fibers are elastomeric despite their high degree of molecular ordering. These results have inspired a variety of molecular models for fibrin’s elasticity, ranging from reversible protein unfolding to rubber-like elasticity. An important property that has not been explored is the timescale of elastic recoil, a parameter that is critical for fibrin’s mechanical function and places a temporal constraint on molecular models of fiber elasticity. Using high-frame-rate imaging and atomic force microscopy-based nanomanipulation, we measured the recoil dynamics of individual fibrin fibers and found that the recoil was orders of magnitude faster than anticipated from models involving protein refolding. We also performed steered discrete molecular-dynamics simulations to investigate the molecular origins of the observed recoil. Our results point to the unstructured αC regions of the otherwise structured fibrin molecule as being responsible for the elastic recoil of the fibers. PMID:23790375

Learning from Demonstration for Autonomous Navigation in Complex Unstructured Terrain

DTIC Science & Technology

2010-06-24

unstructured terrain Seraji and Howard, 2002, Huertas et al., 2005, Biesiadecki and Maimone, 2006] The common thread amongst these approaches is that they con...can be gathered either of- fline [ Seraji and Howard, 2002, Howard et al., 2007] or online [Thrun et al., 2006, Sun et al., 2007] by ob- serving where... Fe = F∗ = ~0; foreach P ie do P i∗ = planLossAugPath(start(P i e), goal(P ie), M); foreach x ∈ P ie do Fe + = Fe + Fx; foreach x ∈ P i∗ do F∗ = F∗ + Fx

Quality assessment of two- and three-dimensional unstructured meshes and validation of an upwind Euler flow solver

NASA Technical Reports Server (NTRS)

Woodard, Paul R.; Batina, John T.; Yang, Henry T. Y.

1992-01-01

Quality assessment procedures are described for two-dimensional unstructured meshes. The procedures include measurement of minimum angles, element aspect ratios, stretching, and element skewness. Meshes about the ONERA M6 wing and the Boeing 747 transport configuration are generated using an advancing front method grid generation package of programs. Solutions of Euler's equations for these meshes are obtained at low angle-of-attack, transonic conditions. Results for these cases, obtained as part of a validation study demonstrate accuracy of an implicit upwind Euler solution algorithm.

Data Storing Proposal from Heterogeneous Systems into a Specialized Repository

NASA Astrophysics Data System (ADS)

Václavová, Andrea; Tanuška, Pavol; Jánošík, Ján

2016-12-01

The aim of this paper is to analyze and to propose an appropriate system for processing and simultaneously storing a vast volume of structured and unstructured data. The paper consists of three parts. The first part addresses the issue of structured and unstructured data. The second part provides the detailed analysis of data repositories and subsequent evaluation indicating which system would be for the given type and volume of data optimal. The third part focuses on the use of gathered information to transfer data to the proposed repository.

Unstructured-grid methods development: Lessons le arned

NASA Technical Reports Server (NTRS)

Batina, John T.

1991-01-01

The development is summarized of unstructured grid methods for the solution of the equations of fluid flow and some of the lessons learned are shared. The 3-D Euler equations are solved, including spatial discretizations, temporal discretizations, and boundary conditions. An example calculation with an upwind implicit method using a CFL (Courant Friedricks Lewy) number of infinity is presented for the Boeing 747 aircraft. The results obtained in less than one hour of CPU time on a Cray-2 computer, thus demonstrating the speed and robustness of the present capability.

Parametric robust control and system identification: Unified approach

NASA Technical Reports Server (NTRS)

Keel, Leehyun

1994-01-01

Despite significant advancement in the area of robust parametric control, the problem of synthesizing such a controller is still a wide open problem. Thus, we attempt to give a solution to this important problem. Our approach captures the parametric uncertainty as an H(sub infinity) unstructured uncertainty so that H(sub infinity) synthesis techniques are applicable. Although the techniques cannot cope with the exact parametric uncertainty, they give a reasonable guideline to model the unstructured uncertainty that contains the parametric uncertainty. An additional loop shaping technique is also introduced to relax its conservatism.

3D Feature Extraction for Unstructured Grids

NASA Technical Reports Server (NTRS)

Silver, Deborah

1996-01-01

Visualization techniques provide tools that help scientists identify observed phenomena in scientific simulation. To be useful, these tools must allow the user to extract regions, classify and visualize them, abstract them for simplified representations, and track their evolution. Object Segmentation provides a technique to extract and quantify regions of interest within these massive datasets. This article explores basic algorithms to extract coherent amorphous regions from two-dimensional and three-dimensional scalar unstructured grids. The techniques are applied to datasets from Computational Fluid Dynamics and those from Finite Element Analysis.

Quantitative Analysis of Hepatitis C NS5A Viral Protein Dynamics on the ER Surface.

PubMed

Knodel, Markus M; Nägel, Arne; Reiter, Sebastian; Vogel, Andreas; Targett-Adams, Paul; McLauchlan, John; Herrmann, Eva; Wittum, Gabriel

2018-01-08

Exploring biophysical properties of virus-encoded components and their requirement for virus replication is an exciting new area of interdisciplinary virological research. To date, spatial resolution has only rarely been analyzed in computational/biophysical descriptions of virus replication dynamics. However, it is widely acknowledged that intracellular spatial dependence is a crucial component of virus life cycles. The hepatitis C virus-encoded NS5A protein is an endoplasmatic reticulum (ER)-anchored viral protein and an essential component of the virus replication machinery. Therefore, we simulate NS5A dynamics on realistic reconstructed, curved ER surfaces by means of surface partial differential equations (sPDE) upon unstructured grids. We match the in silico NS5A diffusion constant such that the NS5A sPDE simulation data reproduce experimental NS5A fluorescence recovery after photobleaching (FRAP) time series data. This parameter estimation yields the NS5A diffusion constant. Such parameters are needed for spatial models of HCV dynamics, which we are developing in parallel but remain qualitative at this stage. Thus, our present study likely provides the first quantitative biophysical description of the movement of a viral component. Our spatio-temporal resolved ansatz paves new ways for understanding intricate spatial-defined processes central to specfic aspects of virus life cycles.

Characterization of an RNA aptamer against HPV-16 L1 virus-like particles.

PubMed

Leija-Montoya, Ana Gabriela; Benítez-Hess, María Luisa; Toscano-Garibay, Julia Dolores; Alvarez-Salas, Luis Marat

2014-10-01

The human papillomavirus (HPV) capsid is mainly composed of the L1 protein that can self-assemble into virus-like particles (VLPs) that are structurally and immunologically similar to the infectious virions. We report here the characterization of RNA aptamers that recognize baculovirus-produced HPV-16 L1 VLPs. Interaction and slot-blot binding assays showed that all isolated aptamers efficiently bound HPV-16 VLPs, although the Sc5-c3 aptamer showed the highest specificity and affinity (Kd=0.05 pM). Sc5-c3 secondary structure consisted of a hairpin with a symmetric bubble and an unstructured 3'end. Biochemical and genetic analyses showed that the Sc5-c3 main loop is directly involved on VLPs binding. In particular, binding specificity appeared mediated by five non-consecutive nucleotide positions. Experiments using bacterial-produced HPV-16 L1 resulted in low Sc5-c3 binding, suggesting that recognition of HPV-16 L1 VLPs relies on quaternary structure features not present in bacteria-produced L1 protein. Sc5-c3 produced specific and stable binding to HPV-16 L1 VLPs even in biofluid protein mixes and thus it may provide a potential diagnostic tool for active HPV infection.

Characterization of an RNA Aptamer Against HPV-16 L1 Virus-Like Particles

PubMed Central

Leija-Montoya, Ana Gabriela; Benítez-Hess, María Luisa; Toscano-Garibay, Julia Dolores

2014-01-01

The human papillomavirus (HPV) capsid is mainly composed of the L1 protein that can self-assemble into virus-like particles (VLPs) that are structurally and immunologically similar to the infectious virions. We report here the characterization of RNA aptamers that recognize baculovirus-produced HPV-16 L1 VLPs. Interaction and slot-blot binding assays showed that all isolated aptamers efficiently bound HPV-16 VLPs, although the Sc5-c3 aptamer showed the highest specificity and affinity (Kd=0.05 pM). Sc5-c3 secondary structure consisted of a hairpin with a symmetric bubble and an unstructured 3′end. Biochemical and genetic analyses showed that the Sc5-c3 main loop is directly involved on VLPs binding. In particular, binding specificity appeared mediated by five non-consecutive nucleotide positions. Experiments using bacterial-produced HPV-16 L1 resulted in low Sc5-c3 binding, suggesting that recognition of HPV-16 L1 VLPs relies on quaternary structure features not present in bacteria-produced L1 protein. Sc5-c3 produced specific and stable binding to HPV-16 L1 VLPs even in biofluid protein mixes and thus it may provide a potential diagnostic tool for active HPV infection. PMID:25111024

Chemical shift assignments of the first and second RRMs of Nrd1, a fission yeast MAPK-target RNA binding protein.

PubMed

Kobayashi, Ayaho; Kanaba, Teppei; Satoh, Ryosuke; Ito, Yutaka; Sugiura, Reiko; Mishima, Masaki

2017-10-01

Negative regulator differentiation 1 (Nrd1), a fission yeast RNA binding protein, modulates cytokinesis and sexual development and contributes to stress granule formation in response to environmental stresses. Nrd1 comprises four RRM domains and binds and stabilizes Cdc4 mRNA that encodes the myosin II light chain. Nrd1 binds the Cpc2 fission-yeast RACK1 homolog, and the interaction promotes Nrd1 localization to stress granules. Interestingly, Pmk1 mitogen-activated protein kinase phosphorylates Thr40 in the unstructured N-terminal region and Thr126 in the first RRM domain of Nrd1. Phosphorylation significantly reduces RNA-binding activity and likely modulates Nrd1 function. To reveal the relationship between the structure and function of Nrd1 and how phosphorylation affects structure, we used heteronuclear NMR techniques to investigate the three-dimensional structure of Nrd1. Here we report the 1 H, 13 C, and 15 N resonance assignments of RRM1-RRM2 (residues 108-284) comprising the first and second RRMs obtained using heteronuclear NMR techniques. Secondary structures derived from the chemical shifts are reported. These data should contribute to the understanding of the three-dimensional structure of the RRM1-RRM2 region of Nrd1 and the perturbation caused by phosphorylation.

Quantitative Analysis of Hepatitis C NS5A Viral Protein Dynamics on the ER Surface

PubMed Central

Nägel, Arne; Reiter, Sebastian; Vogel, Andreas; McLauchlan, John; Herrmann, Eva; Wittum, Gabriel

2018-01-01

Exploring biophysical properties of virus-encoded components and their requirement for virus replication is an exciting new area of interdisciplinary virological research. To date, spatial resolution has only rarely been analyzed in computational/biophysical descriptions of virus replication dynamics. However, it is widely acknowledged that intracellular spatial dependence is a crucial component of virus life cycles. The hepatitis C virus-encoded NS5A protein is an endoplasmatic reticulum (ER)-anchored viral protein and an essential component of the virus replication machinery. Therefore, we simulate NS5A dynamics on realistic reconstructed, curved ER surfaces by means of surface partial differential equations (sPDE) upon unstructured grids. We match the in silico NS5A diffusion constant such that the NS5A sPDE simulation data reproduce experimental NS5A fluorescence recovery after photobleaching (FRAP) time series data. This parameter estimation yields the NS5A diffusion constant. Such parameters are needed for spatial models of HCV dynamics, which we are developing in parallel but remain qualitative at this stage. Thus, our present study likely provides the first quantitative biophysical description of the movement of a viral component. Our spatio-temporal resolved ansatz paves new ways for understanding intricate spatial-defined processes central to specfic aspects of virus life cycles. PMID:29316722

Tropomodulins: pointed-end capping proteins that regulate actin filament architecture in diverse cell types

PubMed Central

Yamashiro, Sawako; Gokhin, David S.; Kimura, Sumiko; Nowak, Roberta B.; Fowler, Velia M.

2012-01-01

Tropomodulins are a family of four proteins (Tmods 1–4) that cap the pointed ends of actin filaments in actin cytoskeletal structures in a developmentally regulated and tissue-specific manner. Unique among capping proteins, Tmods also bind tropomyosins (TMs), which greatly enhance the actin filament pointed-end capping activity of Tmods. Tmods are defined by a tropomyosin (TM)-regulated/Pointed-End Actin Capping (TM-Cap) domain in their unstructured N-terminal portion, followed by a compact, folded Leucine-Rich Repeat/Pointed-End Actin Capping (LRR-Cap) domain. By inhibiting actin monomer association and dissociation from pointed ends, Tmods regulate regulate actin dynamics and turnover, stabilizing actin filament lengths and cytoskeletal architecture. In this review, we summarize the genes, structural features, molecular and biochemical properties, actin regulatory mechanisms, expression patterns, and cell and tissue functions of Tmods. By understanding Tmods’ functions in the context of their molecular structure, actin regulation, binding partners, and related variants (leiomodins 1–3), we can draw broad conclusions that can explain the diverse morphological and functional phenotypes that arise from Tmod perturbation experiments in vitro and in vivo. Tmod-based stabilization and organization of intracellular actin filament networks provide key insights into how the emergent properties of the actin cytoskeleton drive tissue morphogenesis and physiology. PMID:22488942

Cotranslocational processing of the protein substrate calmodulin by an AAA+ unfoldase occurs via unfolding and refolding intermediates.

PubMed

Augustyniak, Rafal; Kay, Lewis E

2018-05-22

Protein remodeling by AAA+ enzymes is central for maintaining proteostasis in a living cell. However, a detailed structural description of how this is accomplished at the level of the substrate molecules that are acted upon is lacking. Here, we combine chemical cross-linking and methyl transverse relaxation-optimized NMR spectroscopy to study, at atomic resolution, the stepwise unfolding and subsequent refolding of the two-domain substrate calmodulin by the VAT AAA+ unfoldase from Thermoplasma acidophilum By engineering intermolecular disulphide bridges between the substrate and VAT we trap the substrate at different stages of translocation, allowing structural studies throughout the translocation process. Our results show that VAT initiates substrate translocation by pulling on intrinsically unstructured N or C termini of substrate molecules without showing specificity for a particular amino acid sequence. Although the B1 domain of protein G is shown to unfold cooperatively, translocation of calmodulin leads to the formation of intermediates, and these differ on an individual domain level in a manner that depends on whether pulling is from the N or C terminus. The approach presented generates an atomic resolution picture of substrate unfolding and subsequent refolding by unfoldases that can be quite different from results obtained via in vitro denaturation experiments.

The intracellular region of ClC-3 chloride channel is in a partially folded state and a monomer.

PubMed

Li, Shu Jie; Kawazaki, Masanobu; Ogasahara, Kyoko; Nakagawa, Atsushi

2006-05-01

In contrast to bacterial ClC chloride channels, all eukaryotic ClC chloride channels have a conserved long intracellular region that makes up of the carboxyl terminus of the protein and is necessary for channel functions as a channel gate. Little is known, however, about the molecular structure of the intracellular region of ClC chloride channels so far. Here, for the first time, we have expressed and purified the intracellular region of the rat ClC-3 chloride channel (C-ClC-3) as a water-soluble protein under physiological conditions, and investigated its structural characteristics and assembly behavior by means of circular dichroism (CD) spectroscopy, differential scanning calorimetry (DSC), size exclusion chromatography and analytical ultracentrifugation. The far-UV CD spectra of C-ClC-3 in the native state and in the presence of urea clearly show that the protein has a significantly folded secondary structure consisting of alpha-helices and beta-sheets, while the near-UV CD spectra and DSC experiments indicate the protein is deficient in well-defined tertiary packing. Its Stokes radius is larger than its expected size as a folded globular protein, as determined on size exclusion chromatography. Furthermore, the DisEMBL program, a useful computational tool for the prediction of disordered/unstructured regions within a protein sequence, predicts that the protein is in a partially folded state. Based on these results, we conclude that C-ClC-3 is partially folded. On the other hand, both size exclusion chromatography and sedimentation equilibrium analysis show that C-ClC-3 exists as a monomer in solution, not a dimer like the whole ClC-3 molecule.

New Developments in the SCIAMACHY L2 Ground Processor

NASA Astrophysics Data System (ADS)

Gretschany, S.; Lichtenberg, G.; Meringer, M.; Theys, N.; Lerot, C.; Eichmann, K.-U.; Liebing, P.; Noel, S.; Dehn, A.; Fehr, T.

2016-08-01

SCIAMACHY (SCanning Imaging Absorption spectroMeter for Atmospheric ChartographY) aboard ESA's environmental satellite ENVISAT observed the Earth's atmosphere in limb, nadir, and solar/lunar occultation geometries covering the UV-Visible to NIR spectral range. It is a joint project of Germany, the Netherlands and Belgium and was launched in February 2002. SCIAMACHY doubled its originally planned in-orbit lifetime of five years before the communication to ENVISAT was severed in April 2012, and the mission entered its post- operational phase F.The SCIAMACHY Quality Working Group (SQWG) was established in 2007. The group coordinates evolution of algorithms and processors, aiming at improving the quality of the operational data products. University of Bremen (IUP), BIRA, DLR-IMF, SRON (Netherlands Institute for Space Research) and KNMI (The Royal Netherlands Meteorological Institute) are the members providing expertise in this group.In order to preserve the best quality of the outstanding data obtained by SCIAMACHY, data processors are still being updated. This presentation will highlight new developments that are currently being incorporated into the forthcoming Version 7 of ESA's operational Level 2 processor.

Unstructured Cartesian refinement with sharp interface immersed boundary method for 3D unsteady incompressible flows

NASA Astrophysics Data System (ADS)

Angelidis, Dionysios; Chawdhary, Saurabh; Sotiropoulos, Fotis

2016-11-01

A novel numerical method is developed for solving the 3D, unsteady, incompressible Navier-Stokes equations on locally refined fully unstructured Cartesian grids in domains with arbitrarily complex immersed boundaries. Owing to the utilization of the fractional step method on an unstructured Cartesian hybrid staggered/non-staggered grid layout, flux mismatch and pressure discontinuity issues are avoided and the divergence free constraint is inherently satisfied to machine zero. Auxiliary/hanging nodes are used to facilitate the discretization of the governing equations. The second-order accuracy of the solver is ensured by using multi-dimension Lagrange interpolation operators and appropriate differencing schemes at the interface of regions with different levels of refinement. The sharp interface immersed boundary method is augmented with local near-boundary refinement to handle arbitrarily complex boundaries. The discrete momentum equation is solved with the matrix free Newton-Krylov method and the Krylov-subspace method is employed to solve the Poisson equation. The second-order accuracy of the proposed method on unstructured Cartesian grids is demonstrated by solving the Poisson equation with a known analytical solution. A number of three-dimensional laminar flow simulations of increasing complexity illustrate the ability of the method to handle flows across a range of Reynolds numbers and flow regimes. Laminar steady and unsteady flows past a sphere and the oblique vortex shedding from a circular cylinder mounted between two end walls demonstrate the accuracy, the efficiency and the smooth transition of scales and coherent structures across refinement levels. Large-eddy simulation (LES) past a miniature wind turbine rotor, parameterized using the actuator line approach, indicates the ability of the fully unstructured solver to simulate complex turbulent flows. Finally, a geometry resolving LES of turbulent flow past a complete hydrokinetic turbine illustrates the potential of the method to simulate turbulent flows past geometrically complex bodies on locally refined meshes. In all the cases, the results are found to be in very good agreement with published data and savings in computational resources are achieved.

An implicit higher-order spatially accurate scheme for solving time dependent flows on unstructured meshes

NASA Astrophysics Data System (ADS)

Tomaro, Robert F.

1998-07-01

The present research is aimed at developing a higher-order, spatially accurate scheme for both steady and unsteady flow simulations using unstructured meshes. The resulting scheme must work on a variety of general problems to ensure the creation of a flexible, reliable and accurate aerodynamic analysis tool. To calculate the flow around complex configurations, unstructured grids and the associated flow solvers have been developed. Efficient simulations require the minimum use of computer memory and computational times. Unstructured flow solvers typically require more computer memory than a structured flow solver due to the indirect addressing of the cells. The approach taken in the present research was to modify an existing three-dimensional unstructured flow solver to first decrease the computational time required for a solution and then to increase the spatial accuracy. The terms required to simulate flow involving non-stationary grids were also implemented. First, an implicit solution algorithm was implemented to replace the existing explicit procedure. Several test cases, including internal and external, inviscid and viscous, two-dimensional, three-dimensional and axi-symmetric problems, were simulated for comparison between the explicit and implicit solution procedures. The increased efficiency and robustness of modified code due to the implicit algorithm was demonstrated. Two unsteady test cases, a plunging airfoil and a wing undergoing bending and torsion, were simulated using the implicit algorithm modified to include the terms required for a moving and/or deforming grid. Secondly, a higher than second-order spatially accurate scheme was developed and implemented into the baseline code. Third- and fourth-order spatially accurate schemes were implemented and tested. The original dissipation was modified to include higher-order terms and modified near shock waves to limit pre- and post-shock oscillations. The unsteady cases were repeated using the higher-order spatially accurate code. The new solutions were compared with those obtained using the second-order spatially accurate scheme. Finally, the increased efficiency of using an implicit solution algorithm in a production Computational Fluid Dynamics flow solver was demonstrated for steady and unsteady flows. A third- and fourth-order spatially accurate scheme has been implemented creating a basis for a state-of-the-art aerodynamic analysis tool.

Aerodynamic Shape Sensitivity Analysis and Design Optimization of Complex Configurations Using Unstructured Grids

NASA Technical Reports Server (NTRS)

Taylor, Arthur C., III; Newman, James C., III; Barnwell, Richard W.

1997-01-01

A three-dimensional unstructured grid approach to aerodynamic shape sensitivity analysis and design optimization has been developed and is extended to model geometrically complex configurations. The advantage of unstructured grids (when compared with a structured-grid approach) is their inherent ability to discretize irregularly shaped domains with greater efficiency and less effort. Hence, this approach is ideally suited for geometrically complex configurations of practical interest. In this work the nonlinear Euler equations are solved using an upwind, cell-centered, finite-volume scheme. The discrete, linearized systems which result from this scheme are solved iteratively by a preconditioned conjugate-gradient-like algorithm known as GMRES for the two-dimensional geometry and a Gauss-Seidel algorithm for the three-dimensional; similar procedures are used to solve the accompanying linear aerodynamic sensitivity equations in incremental iterative form. As shown, this particular form of the sensitivity equation makes large-scale gradient-based aerodynamic optimization possible by taking advantage of memory efficient methods to construct exact Jacobian matrix-vector products. Simple parameterization techniques are utilized for demonstrative purposes. Once the surface has been deformed, the unstructured grid is adapted by considering the mesh as a system of interconnected springs. Grid sensitivities are obtained by differentiating the surface parameterization and the grid adaptation algorithms with ADIFOR (which is an advanced automatic-differentiation software tool). To demonstrate the ability of this procedure to analyze and design complex configurations of practical interest, the sensitivity analysis and shape optimization has been performed for a two-dimensional high-lift multielement airfoil and for a three-dimensional Boeing 747-200 aircraft.

Conformation of a Group 2 Late Embryogenesis Abundant Protein from Soybean. Evidence of Poly (l-Proline)-type II Structure1

PubMed Central

Soulages, Jose L.; Kim, Kangmin; Arrese, Estela L.; Walters, Christina; Cushman, John C.

2003-01-01

Late embryogenesis abundant (LEA) proteins are members of a large group of hydrophilic, glycine-rich proteins found in plants, algae, fungi, and bacteria known collectively as hydrophilins that are preferentially expressed in response to dehydration or hyperosmotic stress. Group 2 LEA (dehydrins or responsive to abscisic acid) proteins are postulated to stabilize macromolecules against damage by freezing, dehydration, ionic, or osmotic stress. However, the structural and physicochemical properties of group 2 LEA proteins that account for such functions remain unknown. We have analyzed the structural properties of a recombinant form of a soybean (Glycine max) group 2 LEA (rGmDHN1). Differential scanning calorimetry of purified rGmDHN1 demonstrated that the protein does not display a cooperative unfolding transition upon heating. Ultraviolet absorption and circular dichroism spectroscopy revealed that the protein is in a largely hydrated and unstructured conformation in solution. However, ultraviolet absorption and circular dichroism measurements collected at different temperatures showed that the protein exists in equilibrium between two extended conformational states: unordered and left-handed extended helical or poly (l-proline)-type II structures. It is estimated that 27% of the residues of rGmDHN1 adopt or poly (l-proline)-type II-like helical conformation at 12°C. The content of extended helix gradually decreases to 15% as the temperature is increased to 80°C. Studies of the conformation of the protein in solution in the presence of liposomes, trifluoroethanol, and sodium dodecyl sulfate indicated that rGmDHN1 has a very low intrinsic ability to adopt α-helical structure and to interact with phospholipid bilayers through amphipathic α-helices. The ability of the protein to remain in a highly extended conformation at low temperatures could constitute the basis of the functional role of GmDHN1 in the prevention of freezing, desiccation, ionic, or osmotic stress-related damage to macromolecular structures. PMID:12644649

Parallel SOR methods with a parabolic-diffusion acceleration technique for solving an unstructured-grid Poisson equation on 3D arbitrary geometries

NASA Astrophysics Data System (ADS)

Zapata, M. A. Uh; Van Bang, D. Pham; Nguyen, K. D.

2016-05-01

This paper presents a parallel algorithm for the finite-volume discretisation of the Poisson equation on three-dimensional arbitrary geometries. The proposed method is formulated by using a 2D horizontal block domain decomposition and interprocessor data communication techniques with message passing interface. The horizontal unstructured-grid cells are reordered according to the neighbouring relations and decomposed into blocks using a load-balanced distribution to give all processors an equal amount of elements. In this algorithm, two parallel successive over-relaxation methods are presented: a multi-colour ordering technique for unstructured grids based on distributed memory and a block method using reordering index following similar ideas of the partitioning for structured grids. In all cases, the parallel algorithms are implemented with a combination of an acceleration iterative solver. This solver is based on a parabolic-diffusion equation introduced to obtain faster solutions of the linear systems arising from the discretisation. Numerical results are given to evaluate the performances of the methods showing speedups better than linear.

Irreconcilable difference between quantum walks and adiabatic quantum computing

NASA Astrophysics Data System (ADS)

Wong, Thomas G.; Meyer, David A.

2016-06-01

Continuous-time quantum walks and adiabatic quantum evolution are two general techniques for quantum computing, both of which are described by Hamiltonians that govern their evolutions by Schrödinger's equation. In the former, the Hamiltonian is fixed, while in the latter, the Hamiltonian varies with time. As a result, their formulations of Grover's algorithm evolve differently through Hilbert space. We show that this difference is fundamental; they cannot be made to evolve along each other's path without introducing structure more powerful than the standard oracle for unstructured search. For an adiabatic quantum evolution to evolve like the quantum walk search algorithm, it must interpolate between three fixed Hamiltonians, one of which is complex and introduces structure that is stronger than the oracle for unstructured search. Conversely, for a quantum walk to evolve along the path of the adiabatic search algorithm, it must be a chiral quantum walk on a weighted, directed star graph with structure that is also stronger than the oracle for unstructured search. Thus, the two techniques, although similar in being described by Hamiltonians that govern their evolution, compute by fundamentally irreconcilable means.

Towards a new multiscale air quality transport model using the fully unstructured anisotropic adaptive mesh technology of Fluidity (version 4.1.9)

NASA Astrophysics Data System (ADS)

Zheng, J.; Zhu, J.; Wang, Z.; Fang, F.; Pain, C. C.; Xiang, J.

2015-10-01

An integrated method of advanced anisotropic hr-adaptive mesh and discretization numerical techniques has been, for first time, applied to modelling of multiscale advection-diffusion problems, which is based on a discontinuous Galerkin/control volume discretization on unstructured meshes. Over existing air quality models typically based on static-structured grids using a locally nesting technique, the advantage of the anisotropic hr-adaptive model has the ability to adapt the mesh according to the evolving pollutant distribution and flow features. That is, the mesh resolution can be adjusted dynamically to simulate the pollutant transport process accurately and effectively. To illustrate the capability of the anisotropic adaptive unstructured mesh model, three benchmark numerical experiments have been set up for two-dimensional (2-D) advection phenomena. Comparisons have been made between the results obtained using uniform resolution meshes and anisotropic adaptive resolution meshes. Performance achieved in 3-D simulation of power plant plumes indicates that this new adaptive multiscale model has the potential to provide accurate air quality modelling solutions effectively.

A bias correction for covariance estimators to improve inference with generalized estimating equations that use an unstructured correlation matrix.

PubMed

Westgate, Philip M

2013-07-20

Generalized estimating equations (GEEs) are routinely used for the marginal analysis of correlated data. The efficiency of GEE depends on how closely the working covariance structure resembles the true structure, and therefore accurate modeling of the working correlation of the data is important. A popular approach is the use of an unstructured working correlation matrix, as it is not as restrictive as simpler structures such as exchangeable and AR-1 and thus can theoretically improve efficiency. However, because of the potential for having to estimate a large number of correlation parameters, variances of regression parameter estimates can be larger than theoretically expected when utilizing the unstructured working correlation matrix. Therefore, standard error estimates can be negatively biased. To account for this additional finite-sample variability, we derive a bias correction that can be applied to typical estimators of the covariance matrix of parameter estimates. Via simulation and in application to a longitudinal study, we show that our proposed correction improves standard error estimation and statistical inference. Copyright © 2012 John Wiley & Sons, Ltd.

The relation of locus-of-control orientation and task structure to problem-solving performance of sixth-grade student pairs

NASA Astrophysics Data System (ADS)

Main, June Dewey; Budd Rowe, Mary

This study investigated the relationship of locus-of-control orientations and task structure to the science problem-solving performance of 100 same-sex, sixth-grade student pairs. Pairs performed a four-variable problem-solving task, racing cylinders down a ramp in a series of trials to determine the 3 fastest of 18 different cylinders. The task was completed in one of two treatment conditions: the structured condition with moderate cuing and the unstructured condition with minimal cuing. Pairs completed an after-task assessment, predicting the results of proposed cylinder races, to measure the ability to understand and apply task concepts. Overall conclusions were: (1) There was no relationship between locus-of-control orientation and effectiveness of problem-solving strategy; (2) internality was significantly related to higher accuracy on task solutions and on after-task predictions; (3) there was no significant relationship between task structure and effectiveness of problem-solving strategy; (4) solutions to the task were more accurate in the unstructured task condition; (5) internality related to more accurate solutions in the unstructured task condition.

Obstacle Classification and 3D Measurement in Unstructured Environments Based on ToF Cameras

PubMed Central

Yu, Hongshan; Zhu, Jiang; Wang, Yaonan; Jia, Wenyan; Sun, Mingui; Tang, Yandong

2014-01-01

Inspired by the human 3D visual perception system, we present an obstacle detection and classification method based on the use of Time-of-Flight (ToF) cameras for robotic navigation in unstructured environments. The ToF camera provides 3D sensing by capturing an image along with per-pixel 3D space information. Based on this valuable feature and human knowledge of navigation, the proposed method first removes irrelevant regions which do not affect robot's movement from the scene. In the second step, regions of interest are detected and clustered as possible obstacles using both 3D information and intensity image obtained by the ToF camera. Consequently, a multiple relevance vector machine (RVM) classifier is designed to classify obstacles into four possible classes based on the terrain traversability and geometrical features of the obstacles. Finally, experimental results in various unstructured environments are presented to verify the robustness and performance of the proposed approach. We have found that, compared with the existing obstacle recognition methods, the new approach is more accurate and efficient. PMID:24945679

First benchmark of the Unstructured Grid Adaptation Working Group

NASA Technical Reports Server (NTRS)

Ibanez, Daniel; Barral, Nicolas; Krakos, Joshua; Loseille, Adrien; Michal, Todd; Park, Mike

2017-01-01

Unstructured grid adaptation is a technology that holds the potential to improve the automation and accuracy of computational fluid dynamics and other computational disciplines. Difficulty producing the highly anisotropic elements necessary for simulation on complex curved geometries that satisfies a resolution request has limited this technology's widespread adoption. The Unstructured Grid Adaptation Working Group is an open gathering of researchers working on adapting simplicial meshes to conform to a metric field. Current members span a wide range of institutions including academia, industry, and national laboratories. The purpose of this group is to create a common basis for understanding and improving mesh adaptation. We present our first major contribution: a common set of benchmark cases, including input meshes and analytic metric specifications, that are publicly available to be used for evaluating any mesh adaptation code. We also present the results of several existing codes on these benchmark cases, to illustrate their utility in identifying key challenges common to all codes and important differences between available codes. Future directions are defined to expand this benchmark to mature the technology necessary to impact practical simulation workflows.

Efficient Unstructured Cartesian/Immersed-Boundary Method with Local Mesh Refinement to Simulate Flows in Complex 3D Geometries

NASA Astrophysics Data System (ADS)

de Zelicourt, Diane; Ge, Liang; Sotiropoulos, Fotis; Yoganathan, Ajit

2008-11-01

Image-guided computational fluid dynamics has recently gained attention as a tool for predicting the outcome of different surgical scenarios. Cartesian Immersed-Boundary methods constitute an attractive option to tackle the complexity of real-life anatomies. However, when such methods are applied to the branching, multi-vessel configurations typically encountered in cardiovascular anatomies the majority of the grid nodes of the background Cartesian mesh end up lying outside the computational domain, increasing the memory and computational overhead without enhancing the numerical resolution in the region of interest. To remedy this situation, the method presented here superimposes local mesh refinement onto an unstructured Cartesian grid formulation. A baseline unstructured Cartesian mesh is generated by eliminating all nodes that reside in the exterior of the flow domain from the grid structure, and is locally refined in the vicinity of the immersed-boundary. The potential of the method is demonstrated by carrying out systematic mesh refinement studies for internal flow problems ranging in complexity from a 90 deg pipe bend to an actual, patient-specific anatomy reconstructed from magnetic resonance.

Revisiting crash spatial heterogeneity: A Bayesian spatially varying coefficients approach.

PubMed

Xu, Pengpeng; Huang, Helai; Dong, Ni; Wong, S C

2017-01-01

This study was performed to investigate the spatially varying relationships between crash frequency and related risk factors. A Bayesian spatially varying coefficients model was elaborately introduced as a methodological alternative to simultaneously account for the unstructured and spatially structured heterogeneity of the regression coefficients in predicting crash frequencies. The proposed method was appealing in that the parameters were modeled via a conditional autoregressive prior distribution, which involved a single set of random effects and a spatial correlation parameter with extreme values corresponding to pure unstructured or pure spatially correlated random effects. A case study using a three-year crash dataset from the Hillsborough County, Florida, was conducted to illustrate the proposed model. Empirical analysis confirmed the presence of both unstructured and spatially correlated variations in the effects of contributory factors on severe crash occurrences. The findings also suggested that ignoring spatially structured heterogeneity may result in biased parameter estimates and incorrect inferences, while assuming the regression coefficients to be spatially clustered only is probably subject to the issue of over-smoothness. Copyright © 2016 Elsevier Ltd. All rights reserved.

Efficient Unstructured Grid Adaptation Methods for Sonic Boom Prediction

NASA Technical Reports Server (NTRS)

Campbell, Richard L.; Carter, Melissa B.; Deere, Karen A.; Waithe, Kenrick A.

2008-01-01

This paper examines the use of two grid adaptation methods to improve the accuracy of the near-to-mid field pressure signature prediction of supersonic aircraft computed using the USM3D unstructured grid flow solver. The first method (ADV) is an interactive adaptation process that uses grid movement rather than enrichment to more accurately resolve the expansion and compression waves. The second method (SSGRID) uses an a priori adaptation approach to stretch and shear the original unstructured grid to align the grid with the pressure waves and reduce the cell count required to achieve an accurate signature prediction at a given distance from the vehicle. Both methods initially create negative volume cells that are repaired in a module in the ADV code. While both approaches provide significant improvements in the near field signature (< 3 body lengths) relative to a baseline grid without increasing the number of grid points, only the SSGRID approach allows the details of the signature to be accurately computed at mid-field distances (3-10 body lengths) for direct use with mid-field-to-ground boom propagation codes.

A bulk viscosity approach for shock capturing on unstructured grids

NASA Astrophysics Data System (ADS)

Shoeybi, Mohammad; Larsson, Nils Johan; Ham, Frank; Moin, Parviz

2008-11-01

The bulk viscosity approach for shock capturing (Cook and Cabot, JCP, 2005) augments the bulk part of the viscous stress tensor. The intention is to capture shock waves without dissipating turbulent structures. The present work extends and modifies this method for unstructured grids. We propose a method that properly scales the bulk viscosity with the grid spacing normal to the shock for unstructured grid for which the shock is not necessarily aligned with the grid. The magnitude of the strain rate tensor used in the original formulation is replaced with the dilatation, which appears to be more appropriate in the vortical turbulent flow regions (Mani et al., 2008). The original form of the model is found to have an impact on dilatational motions away form the shock wave, which is eliminated by a proposed localization of the bulk viscosity. Finally, to allow for grid adaptation around shock waves, an explicit/implicit time advancement scheme has been developed that adaptively identifies the stiff regions. The full method has been verified with several test cases, including 2D shock-vorticity entropy interaction, homogenous isotropic turbulence, and turbulent flow over a cylinder.

LEAping to conclusions: a computational reanalysis of late embryogenesis abundant proteins and their possible roles.

PubMed

Wise, Michael J

2003-10-29

The late embryogenesis abundant (LEA) proteins cover a number of loosely related groups of proteins, originally found in plants but now being found in non-plant species. Their precise function is unknown, though considerable evidence suggests that LEA proteins are involved in desiccation resistance. Using a number of statistically-based bioinformatics tools the classification of a large set of LEA proteins, covering all Groups, is reexamined together with some previous findings. Searches based on peptide composition return proteins with similar composition to different LEA Groups; keyword clustering is then applied to reveal keywords and phrases suggestive of the Groups' properties. Previous research has suggested that glycine is characteristic of LEA proteins, but it is only highly over-represented in Groups 1 and 2, while alanine, thought characteristic of Group 2, is over-represented in Group 3, 4 and 6 but under-represented in Groups 1 and 2. However, for LEA Groups 1 2 and 3 it is shown that glutamine is very significantly over-represented, while cysteine, phenylalanine, isoleucine, leucine and tryptophan are significantly under-represented. There is also evidence that the Group 4 LEA proteins are more appropriately redistributed to Group 2 and Group 3. Similarly, Group 5 is better found among the Group 3 LEA proteins. There is evidence that Group 2 and Group 3 LEA proteins, though distinct, might be related. This relationship is also evident in the overlapping sets of keywords for the two Groups, emphasising alpha-helical structure and, at a larger scale, filaments, all of which fits well with experimental evidence that proteins from both Groups are natively unstructured, but become structured under stress conditions. The keywords support localisation of LEA proteins both in the nucleus and associated with the cytoskeleton, and a mode of action similar to chaperones, perhaps the cold shock chaperones, via a role in DNA-binding. In general, non-globular and low-complexity proteins, such as the LEA proteins, pose particular challenges in determining their functions and modes of action. Rather than masking off and ignoring low-complexity domains, novel tools and tool combinations are needed which are capable of analysing such proteins in their entirety.

CFD Script for Rapid TPS Damage Assessment

NASA Technical Reports Server (NTRS)

McCloud, Peter

2013-01-01

This grid generation script creates unstructured CFD grids for rapid thermal protection system (TPS) damage aeroheating assessments. The existing manual solution is cumbersome, open to errors, and slow. The invention takes a large-scale geometry grid and its large-scale CFD solution, and creates a unstructured patch grid that models the TPS damage. The flow field boundary condition for the patch grid is then interpolated from the large-scale CFD solution. It speeds up the generation of CFD grids and solutions in the modeling of TPS damages and their aeroheating assessment. This process was successfully utilized during STS-134.

On the role of dimensionality and sample size for unstructured and structured covariance matrix estimation

NASA Technical Reports Server (NTRS)

Morgera, S. D.; Cooper, D. B.

1976-01-01

The experimental observation that a surprisingly small sample size vis-a-vis dimension is needed to achieve good signal-to-interference ratio (SIR) performance with an adaptive predetection filter is explained. The adaptive filter requires estimates as obtained by a recursive stochastic algorithm of the inverse of the filter input data covariance matrix. The SIR performance with sample size is compared for the situations where the covariance matrix estimates are of unstructured (generalized) form and of structured (finite Toeplitz) form; the latter case is consistent with weak stationarity of the input data stochastic process.

Application of a Scalable, Parallel, Unstructured-Grid-Based Navier-Stokes Solver

NASA Technical Reports Server (NTRS)

Parikh, Paresh

2001-01-01

A parallel version of an unstructured-grid based Navier-Stokes solver, USM3Dns, previously developed for efficient operation on a variety of parallel computers, has been enhanced to incorporate upgrades made to the serial version. The resultant parallel code has been extensively tested on a variety of problems of aerospace interest and on two sets of parallel computers to understand and document its characteristics. An innovative grid renumbering construct and use of non-blocking communication are shown to produce superlinear computing performance. Preliminary results from parallelization of a recently introduced "porous surface" boundary condition are also presented.

In-memory integration of existing software components for parallel adaptive unstructured mesh workflows

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

Smith, Cameron W.; Granzow, Brian; Diamond, Gerrett

Unstructured mesh methods, like finite elements and finite volumes, support the effective analysis of complex physical behaviors modeled by partial differential equations over general threedimensional domains. The most reliable and efficient methods apply adaptive procedures with a-posteriori error estimators that indicate where and how the mesh is to be modified. Although adaptive meshes can have two to three orders of magnitude fewer elements than a more uniform mesh for the same level of accuracy, there are many complex simulations where the meshes required are so large that they can only be solved on massively parallel systems.

In-memory integration of existing software components for parallel adaptive unstructured mesh workflows

DOE PAGES

Smith, Cameron W.; Granzow, Brian; Diamond, Gerrett; ...

2017-01-01

Unstructured mesh methods, like finite elements and finite volumes, support the effective analysis of complex physical behaviors modeled by partial differential equations over general threedimensional domains. The most reliable and efficient methods apply adaptive procedures with a-posteriori error estimators that indicate where and how the mesh is to be modified. Although adaptive meshes can have two to three orders of magnitude fewer elements than a more uniform mesh for the same level of accuracy, there are many complex simulations where the meshes required are so large that they can only be solved on massively parallel systems.

Discontinuous Spectral Difference Method for Conservation Laws on Unstructured Grids

NASA Technical Reports Server (NTRS)

Liu, Yen; Vinokur, Marcel; Wang, Z. J.

2004-01-01

A new, high-order, conservative, and efficient method for conservation laws on unstructured grids is developed. The concept of discontinuous and high-order local representations to achieve conservation and high accuracy is utilized in a manner similar to the Discontinuous Galerkin (DG) and the Spectral Volume (SV) methods, but while these methods are based on the integrated forms of the equations, the new method is based on the differential form to attain a simpler formulation and higher efficiency. A discussion on the Discontinuous Spectral Difference (SD) Method, locations of the unknowns and flux points and numerical results are also presented.

Quality assessment of two- and three-dimensional unstructured meshes and validation of an upwind Euler flow solver

NASA Technical Reports Server (NTRS)

Woodard, Paul R.; Yang, Henry T. Y.; Batina, John T.

1992-01-01

Quality assessment procedures are described for two-dimensional and three-dimensional unstructured meshes. The procedures include measurement of minimum angles, element aspect ratios, stretching, and element skewness. Meshes about the ONERA M6 wing and the Boeing 747 transport configuration are generated using an advancing front method grid generation package of programs. Solutions of Euler's equations for these meshes are obtained at low angle-of-attack, transonic conditions. Results for these cases, obtained as part of a validation study demonstrate the accuracy of an implicit upwind Euler solution algorithm.

Sandia Unstructured Triangle Tabular Interpolation Package v 0.1 beta

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

2013-09-24

The software interpolates tabular data, such as for equations of state, provided on an unstructured triangular grid. In particular, interpolation occurs in a two dimensional space by looking up the triangle in which the desired evaluation point resides and then performing a linear interpolation over the n-tuples associated with the nodes of the chosen triangle. The interface to the interpolation routines allows for automated conversion of units from those tabulated to the desired output units. when multiple tables are included in a data file, new tables may be generated by on-the-fly mixing of the provided tables

A Hierarchical Multiscale Particle Computational Method for Simulation of Nanoscale Flows on 3D Unstructured Grids

DTIC Science & Technology

2009-08-14

3 is presented in Figure 12. These cases simulate the smallest na- nochannels with H = 0.1 /im and correspond to the near free -molecular flow with a...nal energy flux (or heat transfer rate) from a free stream with p, T.S to a flat plate with surface temperature T aligned with the flow is, 25 S2... Simulation of Nanoscale Flows on 3D Unstructured Grids 5a. CONTRACT NUMBER 5b. GRANT NUMBER FA9950-06-1-0236 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S

An Element-Based Concurrent Partitioner for Unstructured Finite Element Meshes

NASA Technical Reports Server (NTRS)

Ding, Hong Q.; Ferraro, Robert D.

1996-01-01

A concurrent partitioner for partitioning unstructured finite element meshes on distributed memory architectures is developed. The partitioner uses an element-based partitioning strategy. Its main advantage over the more conventional node-based partitioning strategy is its modular programming approach to the development of parallel applications. The partitioner first partitions element centroids using a recursive inertial bisection algorithm. Elements and nodes then migrate according to the partitioned centroids, using a data request communication template for unpredictable incoming messages. Our scalable implementation is contrasted to a non-scalable implementation which is a straightforward parallelization of a sequential partitioner.

Correlation-based regularization and gradient operators for (joint) inversion on unstructured meshes

NASA Astrophysics Data System (ADS)

Jordi, Claudio; Doetsch, Joseph; Günther, Thomas; Schmelzbach, Cedric; Robertsson, Johan

2017-04-01

When working with unstructured meshes for geophysical inversions, special attention should be paid to the design of the operators that are used for regularizing the inverse problem and coupling of different property models in joint inversions. Regularization constraints for inversions on unstructured meshes are often defined in a rather ad-hoc manner and usually only involve the cell to which the operator is applied and its direct neighbours. Similarly, most structural coupling operators for joint inversion, such as the popular cross-gradients operator, are only defined in the direct neighbourhood of a cell. As a result, the regularization and coupling length scales and strength of these operators depend on the discretization as well as cell sizes and shape. Especially for unstructured meshes, where the cell sizes vary throughout the model domain, the dependency of the operator on the discretization may lead to artefacts. Designing operators that are based on a spatial correlation model allows to define correlation length scales over which an operator acts (called footprint), reducing the dependency on the discretization and the effects of variable cell sizes. Moreover, correlation-based operators can accommodate for expected anisotropy by using different length scales in horizontal and vertical directions. Correlation-based regularization operators also known as stochastic regularization operators have already been successfully applied to inversions on regular grids. Here, we formulate stochastic operators for unstructured meshes and apply them in 2D surface and 3D cross-well electrical resistivity tomography data inversion examples of layered media. Especially for the synthetic cross-well example, improved inversion results are achieved when stochastic regularization is used instead of a classical smoothness constraint. For the case of cross-gradients operators for joint inversion, the correlation model is used to define the footprint of the operator and weigh the contributions of the property values that are used to calculate the cross-gradients. In a first series of synthetic-data tests, we examined the mesh dependency of the cross-gradients operators. Compared to operators that are only defined in the direct neighbourhood of a cell, the dependency on the cell size of the cross-gradients calculation is markedly reduced when using operators with larger footprints. A second test with synthetic models focussed on the effect of small-scale variabilities of the parameter value on the cross-gradients calculation. Small-scale variabilities that are superimposed on a global trend of the property value can potentially degrade the cross-gradients calculation and destabilize joint inversion. We observe that the cross-gradients from operators with footprints larger than the length scale of the variabilities are less affected compared to operators with a small footprint. In joint inversions on unstructured meshes, we thus expect the correlation-based coupling operators to ensure robust coupling on a physically meaningful scale.

Dynamics of the Tec‐family tyrosine kinase SH3 domains

PubMed Central

Roberts, Justin M.; Tarafdar, Sreya; Joseph, Raji E.; Andreotti, Amy H.; Smithgall, Thomas E.; Engen, John R.

2016-01-01

Abstract The Src Homology 3 (SH3) domain is an important regulatory domain found in many signaling proteins. X‐ray crystallography and NMR structures of SH3 domains are generally conserved but other studies indicate that protein flexibility and dynamics are not. We previously reported that based on hydrogen exchange mass spectrometry (HX MS) studies, there is variable flexibility and dynamics among the SH3 domains of the Src‐family tyrosine kinases and related proteins. Here we have extended our studies to the SH3 domains of the Tec family tyrosine kinases (Itk, Btk, Tec, Txk, Bmx). The SH3 domains of members of this family augment the variety in dynamics observed in previous SH3 domains. Txk and Bmx SH3 were found to be highly dynamic in solution by HX MS and Bmx was unstructured by NMR. Itk and Btk SH3 underwent a clear EX1 cooperative unfolding event, which was localized using pepsin digestion and mass spectrometry after hydrogen exchange labeling. The unfolding was localized to peptide regions that had been previously identified in the Src‐family and related protein SH3 domains, yet the kinetics of unfolding were not. Sequence alignment does not provide an easy explanation for the observed dynamics behavior, yet the similarity of location of EX1 unfolding suggests that higher‐order structural properties may play a role. While the exact reason for such dynamics is not clear, such motions can be exploited in intra‐ and intermolecular binding assays of proteins containing the domains. PMID:26808198

A Cyclin T1 point mutation that abolishes positive transcription elongation factor (P-TEFb) binding to Hexim1 and HIV tat

PubMed Central

2014-01-01

Background The positive transcription elongation factor b (P-TEFb) plays an essential role in activating HIV genome transcription. It is recruited to the HIV LTR promoter through an interaction between the Tat viral protein and its Cyclin T1 subunit. P-TEFb activity is inhibited by direct binding of its subunit Cyclin T (1 or 2) with Hexim (1 or 2), a cellular protein, bound to the 7SK small nuclear RNA. Hexim1 competes with Tat for P-TEFb binding. Results Mutations that impair human Cyclin T1/Hexim1 interaction were searched using systematic mutagenesis of these proteins coupled with a yeast two-hybrid screen for loss of protein interaction. Evolutionary conserved Hexim1 residues belonging to an unstructured peptide located N-terminal of the dimerization domain, were found to be critical for P-TEFb binding. Random mutagenesis of the N-terminal region of Cyclin T1 provided identification of single amino-acid mutations that impair Hexim1 binding in human cells. Furthermore, conservation of critical residues supported the existence of a functional Hexim1 homologue in nematodes. Conclusions Single Cyclin T1 amino-acid mutations that impair Hexim1 binding are located on a groove between the two cyclin folds and define a surface overlapping the HIV-1 Tat protein binding surface. One residue, Y175, in the centre of this groove was identified as essential for both Hexim1 and Tat binding to P-TEFb as well as for HIV transcription. PMID:24985203

Dynamic shaping of cellular membranes by phospholipids and membrane-deforming proteins.

PubMed

Suetsugu, Shiro; Kurisu, Shusaku; Takenawa, Tadaomi

2014-10-01

All cellular compartments are separated from the external environment by a membrane, which consists of a lipid bilayer. Subcellular structures, including clathrin-coated pits, caveolae, filopodia, lamellipodia, podosomes, and other intracellular membrane systems, are molded into their specific submicron-scale shapes through various mechanisms. Cells construct their micro-structures on plasma membrane and execute vital functions for life, such as cell migration, cell division, endocytosis, exocytosis, and cytoskeletal regulation. The plasma membrane, rich in anionic phospholipids, utilizes the electrostatic nature of the lipids, specifically the phosphoinositides, to form interactions with cytosolic proteins. These cytosolic proteins have three modes of interaction: 1) electrostatic interaction through unstructured polycationic regions, 2) through structured phosphoinositide-specific binding domains, and 3) through structured domains that bind the membrane without specificity for particular phospholipid. Among the structured domains, there are several that have membrane-deforming activity, which is essential for the formation of concave or convex membrane curvature. These domains include the amphipathic helix, which deforms the membrane by hemi-insertion of the helix with both hydrophobic and electrostatic interactions, and/or the BAR domain superfamily, known to use their positively charged, curved structural surface to deform membranes. Below the membrane, actin filaments support the micro-structures through interactions with several BAR proteins as well as other scaffold proteins, resulting in outward and inward membrane micro-structure formation. Here, we describe the characteristics of phospholipids, and the mechanisms utilized by phosphoinositides to regulate cellular events. We then summarize the precise mechanisms underlying the construction of membrane micro-structures and their involvements in physiological and pathological processes. Copyright © 2014 the American Physiological Society.

Cross dimerization of amyloid-β and αsynuclein proteins in aqueous environment: a molecular dynamics simulations study.

PubMed

Jose, Jaya C; Chatterjee, Prathit; Sengupta, Neelanjana

2014-01-01

Self-assembly of the intrinsically unstructured proteins, amyloid beta (Aβ) and alpha synclein (αSyn), are associated with Alzheimer's Disease, and Parkinson's and Lewy Body Diseases, respectively. Importantly, pathological overlaps between these neurodegenerative diseases, and the possibilities of interactions between Aβ and αSyn in biological milieu emerge from several recent clinical reports and in vitro studies. Nevertheless, there are very few molecular level studies that have probed the nature of spontaneous interactions between these two sequentially dissimilar proteins and key characteristics of the resulting cross complexes. In this study, we have used atomistic molecular dynamics simulations to probe the possibility of cross dimerization between αSyn1-95 and Aβ1-42, and thereby gain insights into their plausible early assembly pathways in aqueous environment. Our analyses indicate a strong probability of association between the two sequences, with inter-protein attractive electrostatic interactions playing dominant roles. Principal component analysis revealed significant heterogeneity in the strength and nature of the associations in the key interaction modes. In most, the interactions of repeating Lys residues, mainly in the imperfect repeats 'KTKEGV' present in αSyn1-95 were found to be essential for cross interactions and formation of inter-protein salt bridges. Additionally, a hydrophobicity driven interaction mode devoid of salt bridges, where the non-amyloid component (NAC) region of αSyn1-95 came in contact with the hydrophobic core of Aβ1-42 was observed. The existence of such hetero complexes, and therefore hetero assembly pathways may lead to polymorphic aggregates with variations in pathological attributes. Our results provide a perspective on development of therapeutic strategies for preventing pathogenic interactions between these proteins.

Structural Dynamics of the GW182 Silencing Domain Including its RNA Recognition motif (RRM) Revealed by Hydrogen-Deuterium Exchange Mass Spectrometry

NASA Astrophysics Data System (ADS)

Cieplak-Rotowska, Maja K.; Tarnowski, Krzysztof; Rubin, Marcin; Fabian, Marc R.; Sonenberg, Nahum; Dadlez, Michal; Niedzwiecka, Anna

2018-01-01

The human GW182 protein plays an essential role in micro(mi)RNA-dependent gene silencing. miRNA silencing is mediated, in part, by a GW182 C-terminal region called the silencing domain, which interacts with the poly(A) binding protein and the CCR4-NOT deadenylase complex to repress protein synthesis. Structural studies of this GW182 fragment are challenging due to its predicted intrinsically disordered character, except for its RRM domain. However, detailed insights into the properties of proteins containing disordered regions can be provided by hydrogen-deuterium exchange mass spectrometry (HDX/MS). In this work, we applied HDX/MS to define the structural state of the GW182 silencing domain. HDX/MS analysis revealed that this domain is clearly divided into a natively unstructured part, including the CCR4-NOT interacting motif 1, and a distinct RRM domain. The GW182 RRM has a very dynamic structure, since water molecules can penetrate the whole domain in 2 h. The finding of this high structural dynamics sheds new light on the RRM structure. Though this domain is one of the most frequently occurring canonical protein domains in eukaryotes, these results are - to our knowledge - the first HDX/MS characteristics of an RRM. The HDX/MS studies show also that the α2 helix of the RRM can display EX1 behavior after a freezing-thawing cycle. This means that the RRM structure is sensitive to environmental conditions and can change its conformation, which suggests that the state of the RRM containing proteins should be checked by HDX/MS in regard of the conformational uniformity. [Figure not available: see fulltext.

Escherichia coli FtsH (HflB) degrades a membrane-associated TolAI-II-beta-lactamase fusion protein under highly denaturing conditions.

PubMed

Cooper, K W; Baneyx, F

2001-03-01

TolAI--II--beta-lactamase, a fusion protein consisting of the inner membrane and transperiplasmic domains of TolA followed by TEM--beta-lactamase associated with the inner membrane but remained confined to the cytoplasm when expressed at high level in Escherichia coli. Although the fusion protein was resistant to proteolysis in vivo, it was hydrolyzed during preparative SDS-polyacrylamide electrophoresis and when insoluble cellular fractions unfolded with 5 M urea were subjected to microdialysis. Inhibitor profiling studies revealed that both a metallo- and serine protease were involved in TolAI--II--beta-lactamase degradation under denaturing conditions. The in vitro degradation rates of the fusion protein were not affected when insoluble fractions were harvested from a strain lacking protease IV, but were significantly reduced when microdialysis experiments were conducted with material isolated from an isogenic ftsH1 mutant. Adenine nucleotides were not required for degradation, and ATP supplementation did not accelerate the apparent rate of TolAI--II--beta-lactamase hydrolysis under denaturing conditions. Our results indicate that the metalloprotease active site of FtsH remains functional in the presence of 3--5 M urea and suggest that the ATPase and proteolytic activities of FtsH can be uncoupled if the substrate is sufficiently unstructured. Thus, a key role of the FtsH AAA module appears to be the net unfolding of bound substrates so that they can be efficiently engaged by the protease active site. Copyright 2001 Academic Press.

Origins of the Mechanochemical Coupling of Peptide Bond Formation to Protein Synthesis.

PubMed

Fritch, Benjamin; Kosolapov, Andrey; Hudson, Phillip; Nissley, Daniel A; Woodcock, H Lee; Deutsch, Carol; O'Brien, Edward P

2018-04-18

Mechanical forces acting on the ribosome can alter the speed of protein synthesis, indicating that mechanochemistry can contribute to translation control of gene expression. The naturally occurring sources of these mechanical forces, the mechanism by which they are transmitted 10 nm to the ribosome's catalytic core, and how they influence peptide bond formation rates are largely unknown. Here, we identify a new source of mechanical force acting on the ribosome by using in situ experimental measurements of changes in nascent-chain extension in the exit tunnel in conjunction with all-atom and coarse-grained computer simulations. We demonstrate that when the number of residues composing a nascent chain increases, its unstructured segments outside the ribosome exit tunnel generate piconewtons of force that are fully transmitted to the ribosome's P-site. The route of force transmission is shown to be through the nascent polypetide's backbone, not through the wall of the ribosome's exit tunnel. Utilizing quantum mechanical calculations we find that a consequence of such a pulling force is to decrease the transition state free energy barrier to peptide bond formation, indicating that the elongation of a nascent chain can accelerate translation. Since nascent protein segments can start out as largely unfolded structural ensembles, these results suggest a pulling force is present during protein synthesis that can modulate translation speed. The mechanism of force transmission we have identified and its consequences for peptide bond formation should be relevant regardless of the source of the pulling force.

G-quadruplex RNA binding and recognition by the lysine-specific histone demethylase-1 enzyme.

PubMed

Hirschi, Alexander; Martin, William J; Luka, Zigmund; Loukachevitch, Lioudmila V; Reiter, Nicholas J

2016-08-01

Lysine-specific histone demethylase 1 (LSD1) is an essential epigenetic regulator in metazoans and requires the co-repressor element-1 silencing transcription factor (CoREST) to efficiently catalyze the removal of mono- and dimethyl functional groups from histone 3 at lysine positions 4 and 9 (H3K4/9). LSD1 interacts with over 60 regulatory proteins and also associates with lncRNAs (TERRA, HOTAIR), suggesting a regulatory role for RNA in LSD1 function. We report that a stacked, intramolecular G-quadruplex (GQ) forming TERRA RNA (GG[UUAGGG]8UUA) binds tightly to the functional LSD1-CoREST complex (Kd ≈ 96 nM), in contrast to a single GQ RNA unit ([UUAGGG]4U), a GQ DNA ([TTAGGG]4T), or an unstructured single-stranded RNA. Stabilization of a parallel-stranded GQ RNA structure by monovalent potassium ions (K(+)) is required for high affinity binding to the LSD1-CoREST complex. These data indicate that LSD1 can distinguish between RNA and DNA as well as structured versus unstructured nucleotide motifs. Further, cross-linking mass spectrometry identified the primary location of GQ RNA binding within the SWIRM/amine oxidase domain (AOD) of LSD1. An ssRNA binding region adjacent to this GQ binding site was also identified via X-ray crystallography. This RNA binding interface is consistent with kinetic assays, demonstrating that a GQ-forming RNA can serve as a noncompetitive inhibitor of LSD1-catalyzed demethylation. The identification of a GQ RNA binding site coupled with kinetic data suggests that structured RNAs can function as regulatory molecules in LSD1-mediated mechanisms. © 2016 Hirschi et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

G-quadruplex RNA binding and recognition by the lysine-specific histone demethylase-1 enzyme

PubMed Central

Hirschi, Alexander; Martin, William J.; Luka, Zigmund; Loukachevitch, Lioudmila V.; Reiter, Nicholas J.

2016-01-01

Lysine-specific histone demethylase 1 (LSD1) is an essential epigenetic regulator in metazoans and requires the co-repressor element-1 silencing transcription factor (CoREST) to efficiently catalyze the removal of mono- and dimethyl functional groups from histone 3 at lysine positions 4 and 9 (H3K4/9). LSD1 interacts with over 60 regulatory proteins and also associates with lncRNAs (TERRA, HOTAIR), suggesting a regulatory role for RNA in LSD1 function. We report that a stacked, intramolecular G-quadruplex (GQ) forming TERRA RNA (GG[UUAGGG]8UUA) binds tightly to the functional LSD1–CoREST complex (Kd ≈ 96 nM), in contrast to a single GQ RNA unit ([UUAGGG]4U), a GQ DNA ([TTAGGG]4T), or an unstructured single-stranded RNA. Stabilization of a parallel-stranded GQ RNA structure by monovalent potassium ions (K+) is required for high affinity binding to the LSD1–CoREST complex. These data indicate that LSD1 can distinguish between RNA and DNA as well as structured versus unstructured nucleotide motifs. Further, cross-linking mass spectrometry identified the primary location of GQ RNA binding within the SWIRM/amine oxidase domain (AOD) of LSD1. An ssRNA binding region adjacent to this GQ binding site was also identified via X-ray crystallography. This RNA binding interface is consistent with kinetic assays, demonstrating that a GQ-forming RNA can serve as a noncompetitive inhibitor of LSD1-catalyzed demethylation. The identification of a GQ RNA binding site coupled with kinetic data suggests that structured RNAs can function as regulatory molecules in LSD1-mediated mechanisms. PMID:27277658

Local Conformational Stability of HIV-1 gp120 in Unliganded and CD4-Bound States as Defined by Amide Hydrogen/Deuterium Exchange▿ †

PubMed Central

Kong, Leopold; Huang, Chih-chin; Coales, Stephen J.; Molnar, Kathleen S.; Skinner, Jeff; Hamuro, Yoshitomo; Kwong, Peter D.

2010-01-01

The binding reaction of the HIV-1 gp120 envelope glycoprotein to the CD4 receptor involves exceptional changes in enthalpy and entropy. Crystal structures of gp120 in unliganded and various ligand-bound states, meanwhile, reveal an inner domain able to fold into diverse conformations, a structurally invariant outer domain, and, in the CD4-bound state, a bridging sheet minidomain. These studies, however, provide only hints as to the flexibility of each state. Here we use amide hydrogen/deuterium exchange coupled to mass spectrometry to provide quantifications of local conformational stability for HIV-1 gp120 in unliganded and CD4-bound states. On average, unliganded core gp120 displayed >10,000-fold slower exchange of backbone-amide hydrogens than a theoretically unstructured protein of the same composition, with binding by CD4 reducing the rate of gp120 amide exchange a further 10-fold. For the structurally constant CD4, alterations in exchange correlated well with alterations in binding surface (P value = 0.0004). For the structurally variable gp120, however, reductions in flexibility extended outside the binding surface, and regions of expected high structural diversity (inner domain/bridging sheet) displayed roughly 20-fold more rapid exchange in the unliganded state than regions of low diversity (outer domain). Thus, despite an extraordinary reduction in entropy, neither unliganded gp120 nor free CD4 was substantially unstructured, suggesting that most of the diverse conformations that make up the gp120 unliganded state are reasonably ordered. The results provide a framework for understanding how local conformational stability influences entropic change, conformational diversity, and structural rearrangements in the gp120-CD4 binding reaction. PMID:20660185

Structuring Legacy Pathology Reports by openEHR Archetypes to Enable Semantic Querying.

PubMed

Kropf, Stefan; Krücken, Peter; Mueller, Wolf; Denecke, Kerstin

2017-05-18

Clinical information is often stored as free text, e.g. in discharge summaries or pathology reports. These documents are semi-structured using section headers, numbered lists, items and classification strings. However, it is still challenging to retrieve relevant documents since keyword searches applied on complete unstructured documents result in many false positive retrieval results. We are concentrating on the processing of pathology reports as an example for unstructured clinical documents. The objective is to transform reports semi-automatically into an information structure that enables an improved access and retrieval of relevant data. The data is expected to be stored in a standardized, structured way to make it accessible for queries that are applied to specific sections of a document (section-sensitive queries) and for information reuse. Our processing pipeline comprises information modelling, section boundary detection and section-sensitive queries. For enabling a focused search in unstructured data, documents are automatically structured and transformed into a patient information model specified through openEHR archetypes. The resulting XML-based pathology electronic health records (PEHRs) are queried by XQuery and visualized by XSLT in HTML. Pathology reports (PRs) can be reliably structured into sections by a keyword-based approach. The information modelling using openEHR allows saving time in the modelling process since many archetypes can be reused. The resulting standardized, structured PEHRs allow accessing relevant data by retrieving data matching user queries. Mapping unstructured reports into a standardized information model is a practical solution for a better access to data. Archetype-based XML enables section-sensitive retrieval and visualisation by well-established XML techniques. Focussing the retrieval to particular sections has the potential of saving retrieval time and improving the accuracy of the retrieval.

Evaluation of the UnTRIM model for 3-D tidal circulation

USGS Publications Warehouse

Cheng, R.T.; Casulli, V.; ,

2001-01-01

A family of numerical models, known as the TRIM models, shares the same modeling philosophy for solving the shallow water equations. A characteristic analysis of the shallow water equations points out that the numerical instability is controlled by the gravity wave terms in the momentum equations and by the transport terms in the continuity equation. A semi-implicit finite-difference scheme has been formulated so that these terms and the vertical diffusion terms are treated implicitly and the remaining terms explicitly to control the numerical stability and the computations are carried out over a uniform finite-difference computational mesh without invoking horizontal or vertical coordinate transformations. An unstructured grid version of TRIM model is introduced, or UnTRIM (pronounces as "you trim"), which preserves these basic numerical properties and modeling philosophy, only the computations are carried out over an unstructured orthogonal grid. The unstructured grid offers the flexibilities in representing complex study areas so that fine grid resolution can be placed in regions of interest, and coarse grids are used to cover the remaining domain. Thus, the computational efforts are concentrated in areas of importance, and an overall computational saving can be achieved because the total number of grid-points is dramatically reduced. To use this modeling approach, an unstructured grid mesh must be generated to properly reflect the properties of the domain of the investigation. The new modeling flexibility in grid structure is accompanied by new challenges associated with issues of grid generation. To take full advantage of this new model flexibility, the model grid generation should be guided by insights into the physics of the problems; and the insights needed may require a higher degree of modeling skill.

SKILLED BIMANUAL TRAINING DRIVES MOTOR CORTEX PLASTICITY IN CHILDREN WITH UNILATERAL CEREBRAL PALSY

PubMed Central

Friel, Kathleen M.; Kuo, Hsing-Ching; Fuller, Jason; Ferre, Claudio L.; Brandão, Marina; Carmel, Jason B.; Bleyenheuft, Yannick; Gowatsky, Jaimie L.; Stanford, Arielle D.; Rowny, Stefan B.; Luber, Bruce; Bassi, Bruce; Murphy, David LK; Lisanby, Sarah H.; Gordon, Andrew M.

2015-01-01

Background Intensive bimanual therapy can improve hand function in children with unilateral spastic cerebral palsy (USCP). We compared the effects of structured bimanual skill training vs. unstructured bimanual practice on motor outcomes and motor map plasticity in children with USCP. Objective We hypothesized that structured skill training would produce greater motor map plasticity than unstructured practice. Methods Twenty children with USCP (average age 9,5; 12 males) received therapy in a day-camp-setting, 6 h/day, 5 days/week, for 3 weeks. In structured skill training (n=10), children performed progressively more difficult movements and practiced functional goals. In unstructured practice (n=10), children engaged in bimanual activities but did not practice skillful movements or functional goals. We used the Assisting Hand Assessment (AHA), Jebsen-Taylor test of Hand Function (JTTHF) and Canadian Occupational Performance Measure (COPM) to measure hand function. We used single-pulse transcranial magnetic stimulation (TMS) to map the representation of first dorsal interosseous (FDI) and flexor carpi radialis (FCR) muscles bilaterally. Results Both groups showed significant improvements in bimanual hand use (AHA; p<0.05) and hand dexterity (JTTHF; p<0.001). However, only the structured skill group showed increases in the size of the affected hand motor map and amplitudes of motor evoked potentials (p<0.01). Most children who showed the most functional improvements (COPM) had the largest changes in map size. Conclusions These findings uncover a dichotomy of plasticity: the unstructured practice group improved hand function but did not show changes in motor maps. Skill training is important for driving motor cortex plasticity in children with USCP. PMID:26867559

Improvements to the Unstructured Mesh Generator MESH3D

NASA Technical Reports Server (NTRS)

Thomas, Scott D.; Baker, Timothy J.; Cliff, Susan E.

1999-01-01

The AIRPLANE process starts with an aircraft geometry stored in a CAD system. The surface is modeled with a mesh of triangles and then the flow solver produces pressures at surface points which may be integrated to find forces and moments. The biggest advantage is that the grid generation bottleneck of the CFD process is eliminated when an unstructured tetrahedral mesh is used. MESH3D is the key to turning around the first analysis of a CAD geometry in days instead of weeks. The flow solver part of AIRPLANE has proven to be robust and accurate over a decade of use at NASA. It has been extensively validated with experimental data and compares well with other Euler flow solvers. AIRPLANE has been applied to all the HSR geometries treated at Ames over the course of the HSR program in order to verify the accuracy of other flow solvers. The unstructured approach makes handling complete and complex geometries very simple because only the surface of the aircraft needs to be discretized, i.e. covered with triangles. The volume mesh is created automatically by MESH3D. AIRPLANE runs well on multiple platforms. Vectorization on the Cray Y-MP is reasonable for a code that uses indirect addressing. Massively parallel computers such as the IBM SP2, SGI Origin 2000, and the Cray T3E have been used with an MPI version of the flow solver and the code scales very well on these systems. AIRPLANE can run on a desktop computer as well. AIRPLANE has a future. The unstructured technologies developed as part of the HSR program are now targeting high Reynolds number viscous flow simulation. The pacing item in this effort is Navier-Stokes mesh generation.

Social-communicative effects of the Picture Exchange Communication System (PECS) in autism spectrum disorders.

PubMed

Lerna, Anna; Esposito, Dalila; Conson, Massimiliano; Russo, Luigi; Massagli, Angelo

2012-01-01

The Picture Exchange Communication System (PECS) is a common treatment choice for non-verbal children with autism. However, little empirical evidence is available on the usefulness of PECS in treating social-communication impairments in autism. To test the effects of PECS on social-communicative skills in children with autism, concurrently taking into account standardized psychometric data, standardized functional assessment of adaptive behaviour, and information on social-communicative variables coded in an unstructured setting. Eighteen preschool children (mean age = 38.78 months) were assigned to two intervention approaches, i.e. PECS and Conventional Language Therapy (CLT). Both PECS (Phases I-IV) and CLT were delivered three times per week, in 30-min sessions, for 6 months. Outcome measures were the following: Autism Diagnostic Observation Schedule (ADOS) domain scores for Communication and Reciprocal Social Interaction; Language and Personal-Social subscales of the Griffiths' Mental Developmental Scales (GMDS); Communication and Social Abilities domains of the Vineland Adaptive Behavior Scales (VABS); and several social-communicative variables coded in an unstructured setting. Results demonstrated that the two groups did not differ at Time 1 (pre-treatment assessment), whereas at Time 2 (post-test) the PECS group showed a significant improvement with respect to the CLT group on the VABS social domain score and on almost all the social-communicative abilities coded in the unstructured setting (i.e. joint attention, request, initiation, cooperative play, but not eye contact). These findings showed that PECS intervention (Phases I-IV) can improve social-communicative skills in children with autism. This improvement is especially evident in standardized measures of adaptive behaviour and measures derived from the observation of children in an unstructured setting. © 2012 Royal College of Speech and Language Therapists.

Cube Kohonen self-organizing map (CKSOM) model with new equations in organizing unstructured data.

PubMed

Lim, Seng Poh; Haron, Habibollah

2013-09-01

Surface reconstruction by using 3-D data is used to represent the surface of an object and perform important tasks. The type of data used is important and can be described as either structured or unstructured. For unstructured data, there is no connectivity information between data points. As a result, incorrect shapes will be obtained during the imaging process. Therefore, the data should be reorganized by finding the correct topology so that the correct shape can be obtained. Previous studies have shown that the Kohonen self-organizing map (KSOM) could be used to solve data organizing problems. However, 2-D Kohonen maps are limited because they are unable to cover the whole surface of closed 3-D surface data. Furthermore, the neurons inside the 3-D KSOM structure should be removed in order to create a correct wireframe model. This is because only the outside neurons are used to represent the surface of an object. The aim of this paper is to use KSOM to organize unstructured data for closed surfaces. KSOM isused in this paper by testing its ability to organize medical image data because KSOM is mostly used in constructing engineering field data. Enhancements are added to the model by introducing class number and the index vector, and new equations are created. Various grid sizes and maximum iterations are tested in the experiments. Based on the results, the number of redundancies is found to be directly proportional to the grid size. When we increase the maximum iterations, the surface of the image becomes smoother. An area formula is used and manual calculations are performed to validate the results. This model is implemented and images are created using Dev C++ and GNUPlot.

Improvement in American Board of Surgery in-training examination performance with a multidisciplinary surgeon-directed integrated learning platform.

PubMed

Dua, Anahita; Sudan, Ranjan; Desai, Sapan S

2014-01-01

The American Board of Surgery In-Training Examination (ABSITE) is a predictor of resident performance on the general surgery-qualifying examination and plays a role in obtaining competitive fellowships. A learning management system (LMS) permits the delivery of a structured curriculum that appeals to the modern resident owing to the ease of accessibility and all-in-one organization. This study hypothesizes that trainees using a structured surgeon-directed LMS will achieve improved ABSITE scores compared with those using an unstructured approach to the examination. A multidisciplinary print and digital review course with practice questions, review textbooks, weekly reading assignments, and slide and audio reviews integrated within an online LMS was made available to postgraduate year (PGY)-3 and PGY-4 residents in 2008 and 2009. Surveys were emailed requesting ABSITE scores to compare outcomes in those trainees that used the course with those who used an unstructured approach. Statistical analysis was conducted via descriptive statistics and Pearson chi-square with p < 0.05 deemed statistically significant. Surveys were mailed to 508 trainees. There was an 80% (408) response rate. Residents who used structured approaches in both the years achieved the highest scores, followed by those who adopted a structured approach in PGY-4. The residents using an unstructured approach in both the years showed no significant improvement. Residents who used a structured LMS performed significantly better than their counterparts who used an unstructured approach. A properly constructed online education curriculum has the potential to improve ABSITE scores. Copyright © 2014 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

Hybrid mesh finite volume CFD code for studying heat transfer in a forward-facing step

NASA Astrophysics Data System (ADS)

Jayakumar, J. S.; Kumar, Inder; Eswaran, V.

2010-12-01

Computational fluid dynamics (CFD) methods employ two types of grid: structured and unstructured. Developing the solver and data structures for a finite-volume solver is easier than for unstructured grids. But real-life problems are too complicated to be fitted flexibly by structured grids. Therefore, unstructured grids are widely used for solving real-life problems. However, using only one type of unstructured element consumes a lot of computational time because the number of elements cannot be controlled. Hence, a hybrid grid that contains mixed elements, such as the use of hexahedral elements along with tetrahedral and pyramidal elements, gives the user control over the number of elements in the domain, and thus only the domain that requires a finer grid is meshed finer and not the entire domain. This work aims to develop such a finite-volume hybrid grid solver capable of handling turbulence flows and conjugate heat transfer. It has been extended to solving flow involving separation and subsequent reattachment occurring due to sudden expansion or contraction. A significant effect of mixing high- and low-enthalpy fluid occurs in the reattached regions of these devices. This makes the study of the backward-facing and forward-facing step with heat transfer an important field of research. The problem of the forward-facing step with conjugate heat transfer was taken up and solved for turbulence flow using a two-equation model of k-ω. The variation in the flow profile and heat transfer behavior has been studied with the variation in Re and solid to fluid thermal conductivity ratios. The results for the variation in local Nusselt number, interface temperature and skin friction factor are presented.

A Focus Group Exploration of Automated Case-Finders to Identify High-Risk Heart Failure Patients Within an Urban Safety Net Hospital.

PubMed

Patterson, Mark E; Miranda, Derick; Schuman, Greg; Eaton, Christopher; Smith, Andrew; Silver, Brad

2016-01-01

Leveraging "big data" as a means of informing cost-effective care holds potential in triaging high-risk heart failure (HF) patients for interventions within hospitals seeking to reduce 30-day readmissions. Explore provider's beliefs and perceptions about using an electronic health record (EHR)-based tool that uses unstructured clinical notes to risk-stratify high-risk heart failure patients. Six providers from an inpatient HF clinic within an urban safety net hospital were recruited to participate in a semistructured focus group. A facilitator led a discussion on the feasibility and value of using an EHR tool driven by unstructured clinical notes to help identify high-risk patients. Data collected from transcripts were analyzed using a thematic analysis that facilitated drawing conclusions clustered around categories and themes. From six categories emerged two themes: (1) challenges of finding valid and accurate results, and (2) strategies used to overcome these challenges. Although employing a tool that uses electronic medical record (EMR) unstructured text as the benchmark by which to identify high-risk patients is efficient, choosing appropriate benchmark groups could be challenging given the multiple causes of readmission. Strategies to mitigate these challenges include establishing clear selection criteria to guide benchmark group composition, and quality outcome goals for the hospital. Prior to implementing into practice an innovative EMR-based case-finder driven by unstructured clinical notes, providers are advised to do the following: (1) define patient quality outcome goals, (2) establish criteria by which to guide benchmark selection, and (3) verify the tool's validity and reliability. Achieving consensus on these issues would be necessary for this innovative EHR-based tool to effectively improve clinical decision-making and in turn, decrease readmissions for high-risk patients.

P1 Nonconforming Finite Element Method for the Solution of Radiation Transport Problems

NASA Technical Reports Server (NTRS)

Kang, Kab S.

2002-01-01

The simulation of radiation transport in the optically thick flux-limited diffusion regime has been identified as one of the most time-consuming tasks within large simulation codes. Due to multimaterial complex geometry, the radiation transport system must often be solved on unstructured grids. In this paper, we investigate the behavior and the benefits of the unstructured P(sub 1) nonconforming finite element method, which has proven to be flexible and effective on related transport problems, in solving unsteady implicit nonlinear radiation diffusion problems using Newton and Picard linearization methods. Key words. nonconforrning finite elements, radiation transport, inexact Newton linearization, multigrid preconditioning

The upwind control volume scheme for unstructured triangular grids

NASA Technical Reports Server (NTRS)

Giles, Michael; Anderson, W. Kyle; Roberts, Thomas W.

1989-01-01

A new algorithm for the numerical solution of the Euler equations is presented. This algorithm is particularly suited to the use of unstructured triangular meshes, allowing geometric flexibility. Solutions are second-order accurate in the steady state. Implementation of the algorithm requires minimal grid connectivity information, resulting in modest storage requirements, and should enhance the implementation of the scheme on massively parallel computers. A novel form of upwind differencing is developed, and is shown to yield sharp resolution of shocks. Two new artificial viscosity models are introduced that enhance the performance of the new scheme. Numerical results for transonic airfoil flows are presented, which demonstrate the performance of the algorithm.

Parallel performance investigations of an unstructured mesh Navier-Stokes solver

NASA Technical Reports Server (NTRS)

Mavriplis, Dimitri J.

2000-01-01

A Reynolds-averaged Navier-Stokes solver based on unstructured mesh techniques for analysis of high-lift configurations is described. The method makes use of an agglomeration multigrid solver for convergence acceleration. Implicit line-smoothing is employed to relieve the stiffness associated with highly stretched meshes. A GMRES technique is also implemented to speed convergence at the expense of additional memory usage. The solver is cache efficient and fully vectorizable, and is parallelized using a two-level hybrid MPI-OpenMP implementation suitable for shared and/or distributed memory architectures, as well as clusters of shared memory machines. Convergence and scalability results are illustrated for various high-lift cases.

Unstructured Cartesian/prismatic grid generation for complex geometries

NASA Technical Reports Server (NTRS)

Karman, Steve L., Jr.

1995-01-01

The generation of a hybrid grid system for discretizing complex three dimensional (3D) geometries is described. The primary grid system is an unstructured Cartesian grid automatically generated using recursive cell subdivision. This grid system is sufficient for computing Euler solutions about extremely complex 3D geometries. A secondary grid system, using triangular-prismatic elements, may be added for resolving the boundary layer region of viscous flows near surfaces of solid bodies. This paper describes the grid generation processes used to generate each grid type. Several example grids are shown, demonstrating the ability of the method to discretize complex geometries, with very little pre-processing required by the user.

A Solution Adaptive Technique Using Tetrahedral Unstructured Grids

NASA Technical Reports Server (NTRS)

Pirzadeh, Shahyar Z.

2000-01-01

An adaptive unstructured grid refinement technique has been developed and successfully applied to several three dimensional inviscid flow test cases. The method is based on a combination of surface mesh subdivision and local remeshing of the volume grid Simple functions of flow quantities are employed to detect dominant features of the flowfield The method is designed for modular coupling with various error/feature analyzers and flow solvers. Several steady-state, inviscid flow test cases are presented to demonstrate the applicability of the method for solving practical three-dimensional problems. In all cases, accurate solutions featuring complex, nonlinear flow phenomena such as shock waves and vortices have been generated automatically and efficiently.

Euler Flow Computations on Non-Matching Unstructured Meshes

NASA Technical Reports Server (NTRS)

Gumaste, Udayan

1999-01-01

Advanced fluid solvers to predict aerodynamic performance-coupled treatment of multiple fields are described. The interaction between the fluid and structural components in the bladed regions of the engine is investigated with respect to known blade failures caused by either flutter or forced vibrations. Methods are developed to describe aeroelastic phenomena for internal flows in turbomachinery by accounting for the increased geometric complexity, mutual interaction between adjacent structural components and presence of thermal and geometric loading. The computer code developed solves the full three dimensional aeroelastic problem of-stage. The results obtained show that flow computations can be performed on non-matching finite-volume unstructured meshes with second order spatial accuracy.

Divergence preserving discrete surface integral methods for Maxwell's curl equations using non-orthogonal unstructured grids

NASA Technical Reports Server (NTRS)

Madsen, Niel K.

1992-01-01

Several new discrete surface integral (DSI) methods for solving Maxwell's equations in the time-domain are presented. These methods, which allow the use of general nonorthogonal mixed-polyhedral unstructured grids, are direct generalizations of the canonical staggered-grid finite difference method. These methods are conservative in that they locally preserve divergence or charge. Employing mixed polyhedral cells, (hexahedral, tetrahedral, etc.) these methods allow more accurate modeling of non-rectangular structures and objects because the traditional stair-stepped boundary approximations associated with the orthogonal grid based finite difference methods can be avoided. Numerical results demonstrating the accuracy of these new methods are presented.

Stable Artificial Dissipation Operators for Finite Volume Schemes on Unstructured Grids

NASA Technical Reports Server (NTRS)

Svard, Magnus; Gong, Jing; Nordstrom, Jan

2006-01-01

Our objective is to derive stable first-, second- and fourth-order artificial dissipation operators for node based finite volume schemes. Of particular interest are general unstructured grids where the strength of the finite volume method is fully utilized. A commonly used finite volume approximation of the Laplacian will be the basis in the construction of the artificial dissipation. Both a homogeneous dissipation acting in all directions with equal strength and a modification that allows different amount of dissipation in different directions are derived. Stability and accuracy of the new operators are proved and the theoretical results are supported by numerical computations.

Functional Equivalence Acceptance Testing of FUN3D for Entry Descent and Landing Applications

NASA Technical Reports Server (NTRS)

Gnoffo, Peter A.; Wood, William A.; Kleb, William L.; Alter, Stephen J.; Glass, Christopher E.; Padilla, Jose F.; Hammond, Dana P.; White, Jeffery A.

2013-01-01

The functional equivalence of the unstructured grid code FUN3D to the the structured grid code LAURA (Langley Aerothermodynamic Upwind Relaxation Algorithm) is documented for applications of interest to the Entry, Descent, and Landing (EDL) community. Examples from an existing suite of regression tests are used to demonstrate the functional equivalence, encompassing various thermochemical models and vehicle configurations. Algorithm modifications required for the node-based unstructured grid code (FUN3D) to reproduce functionality of the cell-centered structured code (LAURA) are also documented. Challenges associated with computation on tetrahedral grids versus computation on structured-grid derived hexahedral systems are discussed.

Implicit solvers for unstructured meshes

NASA Technical Reports Server (NTRS)

Venkatakrishnan, V.; Mavriplis, Dimitri J.

1991-01-01

Implicit methods for unstructured mesh computations are developed and tested. The approximate system which arises from the Newton-linearization of the nonlinear evolution operator is solved by using the preconditioned generalized minimum residual technique. These different preconditioners are investigated: the incomplete LU factorization (ILU), block diagonal factorization, and the symmetric successive over-relaxation (SSOR). The preconditioners have been optimized to have good vectorization properties. The various methods are compared over a wide range of problems. Ordering of the unknowns, which affects the convergence of these sparse matrix iterative methods, is also investigated. Results are presented for inviscid and turbulent viscous calculations on single and multielement airfoil configurations using globally and adaptively generated meshes.

Aerodynamic Design on Unstructured Grids for Turbulent Flows

NASA Technical Reports Server (NTRS)

Anderson, W. Kyle; Bonhaus, Daryl L.

1997-01-01

An aerodynamic design algorithm for turbulent flows using unstructured grids is described. The current approach uses adjoint (costate) variables for obtaining derivatives of the cost function. The solution of the adjoint equations is obtained using an implicit formulation in which the turbulence model is fully coupled with the flow equations when solving for the costate variables. The accuracy of the derivatives is demonstrated by comparison with finite-difference gradients and a few example computations are shown. In addition, a user interface is described which significantly reduces the time required for setting up the design problems. Recommendations on directions of further research into the Navier Stokes design process are made.

Aerodynamic Design Optimization on Unstructured Meshes Using the Navier-Stokes Equations

NASA Technical Reports Server (NTRS)

Nielsen, Eric J.; Anderson, W. Kyle

1998-01-01

A discrete adjoint method is developed and demonstrated for aerodynamic design optimization on unstructured grids. The governing equations are the three-dimensional Reynolds-averaged Navier-Stokes equations coupled with a one-equation turbulence model. A discussion of the numerical implementation of the flow and adjoint equations is presented. Both compressible and incompressible solvers are differentiated and the accuracy of the sensitivity derivatives is verified by comparing with gradients obtained using finite differences. Several simplifying approximations to the complete linearization of the residual are also presented, and the resulting accuracy of the derivatives is examined. Demonstration optimizations for both compressible and incompressible flows are given.

Tree-oriented interactive processing with an application to theorem-proving, appendix E

NASA Technical Reports Server (NTRS)

Hammerslag, David; Kamin, Samuel N.; Campbell, Roy H.

1985-01-01

The concept of unstructured structure editing and ted, an editor for unstructured trees, is described. Ted is used to manipulate hierarchies of information in an unrestricted manner. The tool was implemented and applied to the problem of organizing formal proofs. As a proof management tool, it maintains the validity of a proof and its constituent lemmas independently from the methods used to validate the proof. It includes an adaptable interface which may be used to invoke theorem provers and other aids to proof construction. Using ted, a user may construct, maintain, and verify formal proofs using a variety of theorem provers, proof checkers, and formatters.

An Interpreted Language and System for the Visualization of Unstructured Meshes

NASA Technical Reports Server (NTRS)

Moran, Patrick J.; Gerald-Yamasaki, Michael (Technical Monitor)

1998-01-01

We present an interpreted language and system supporting the visualization of unstructured meshes and the manipulation of shapes defined in terms of mesh subsets. The language features primitives inspired by geometric modeling, mathematical morphology and algebraic topology. The adaptation of the topology ideas to an interpreted environment, along with support for programming constructs such, as user function definition, provide a flexible system for analyzing a mesh and for calculating with shapes defined in terms of the mesh. We present results demonstrating some of the capabilities of the language, based on an implementation called the Shape Calculator, for tetrahedral meshes in R^3.

Higher Order Time Integration Schemes for the Unsteady Navier-Stokes Equations on Unstructured Meshes

NASA Technical Reports Server (NTRS)

Jothiprasad, Giridhar; Mavriplis, Dimitri J.; Caughey, David A.

2002-01-01

The rapid increase in available computational power over the last decade has enabled higher resolution flow simulations and more widespread use of unstructured grid methods for complex geometries. While much of this effort has been focused on steady-state calculations in the aerodynamics community, the need to accurately predict off-design conditions, which may involve substantial amounts of flow separation, points to the need to efficiently simulate unsteady flow fields. Accurate unsteady flow simulations can easily require several orders of magnitude more computational effort than a corresponding steady-state simulation. For this reason, techniques for improving the efficiency of unsteady flow simulations are required in order to make such calculations feasible in the foreseeable future. The purpose of this work is to investigate possible reductions in computer time due to the choice of an efficient time-integration scheme from a series of schemes differing in the order of time-accuracy, and by the use of more efficient techniques to solve the nonlinear equations which arise while using implicit time-integration schemes. This investigation is carried out in the context of a two-dimensional unstructured mesh laminar Navier-Stokes solver.

Implicit flux-split Euler schemes for unsteady aerodynamic analysis involving unstructured dynamic meshes

NASA Technical Reports Server (NTRS)

Batina, John T.

1990-01-01

Improved algorithms for the solution of the time-dependent Euler equations are presented for unsteady aerodynamic analysis involving unstructured dynamic meshes. The improvements have been developed recently to the spatial and temporal discretizations used by unstructured grid flow solvers. The spatial discretization involves a flux-split approach which is naturally dissipative and captures shock waves sharply with at most one grid point within the shock structure. The temporal discretization involves an implicit time-integration shceme using a Gauss-Seidel relaxation procedure which is computationally efficient for either steady or unsteady flow problems. For example, very large time steps may be used for rapid convergence to steady state, and the step size for unsteady cases may be selected for temporal accuracy rather than for numerical stability. Steady and unsteady flow results are presented for the NACA 0012 airfoil to demonstrate applications of the new Euler solvers. The unsteady results were obtained for the airfoil pitching harmonically about the quarter chord. The resulting instantaneous pressure distributions and lift and moment coefficients during a cycle of motion compare well with experimental data. The paper presents a description of the Euler solvers along with results and comparisons which assess the capability.

Effectiveness of objectivist online instruction on graduate learners' knowledge and competence

NASA Astrophysics Data System (ADS)

Maryannakis, Artemios

Online courses currently offered by aeronautical institutions are unstructured conversions of traditional courses into Web-based courses that lack the learning theory and instructional design principles framework, thus lacking the efficiency and effectiveness in dealing with the academic demands required to prepare aviation/aerospace professionals for the challenges of the technologically driven twenty-first century. The purpose of this study was to compare the effectiveness of two versions of an aeronautical online graduate course on research methods knowledge and competence: a comprehensive objectivist design and an unstructured design. Quantitative, causal comparative, quasi-experimental methodology was utilized. Using criteria derived from literature, criteria were established for the development and eventual online delivery of a comprehensive objectivist instructional design on graduate research methods learning. Results revealed that the comprehensive objectivist design was significantly more effective than its unstructured counterpart on graduate learners' competence in research methods, but found no significant difference in knowledge. It was recommended that aeronautical institutions (a) create programs with critical thinking and problem solving embedded in their curriculum for enhancing learner competence, and (b) thoroughly train every online instructor in the development and use of comprehensive online instruction.

An Implicit Upwind Algorithm for Computing Turbulent Flows on Unstructured Grids

NASA Technical Reports Server (NTRS)

Anerson, W. Kyle; Bonhaus, Daryl L.

1994-01-01

An implicit, Navier-Stokes solution algorithm is presented for the computation of turbulent flow on unstructured grids. The inviscid fluxes are computed using an upwind algorithm and the solution is advanced in time using a backward-Euler time-stepping scheme. At each time step, the linear system of equations is approximately solved with a point-implicit relaxation scheme. This methodology provides a viable and robust algorithm for computing turbulent flows on unstructured meshes. Results are shown for subsonic flow over a NACA 0012 airfoil and for transonic flow over a RAE 2822 airfoil exhibiting a strong upper-surface shock. In addition, results are shown for 3 element and 4 element airfoil configurations. For the calculations, two one equation turbulence models are utilized. For the NACA 0012 airfoil, a pressure distribution and force data are compared with other computational results as well as with experiment. Comparisons of computed pressure distributions and velocity profiles with experimental data are shown for the RAE airfoil and for the 3 element configuration. For the 4 element case, comparisons of surface pressure distributions with experiment are made. In general, the agreement between the computations and the experiment is good.

Multigrid Strategies for Viscous Flow Solvers on Anisotropic Unstructured Meshes

NASA Technical Reports Server (NTRS)

Movriplis, Dimitri J.

1998-01-01

Unstructured multigrid techniques for relieving the stiffness associated with high-Reynolds number viscous flow simulations on extremely stretched grids are investigated. One approach consists of employing a semi-coarsening or directional-coarsening technique, based on the directions of strong coupling within the mesh, in order to construct more optimal coarse grid levels. An alternate approach is developed which employs directional implicit smoothing with regular fully coarsened multigrid levels. The directional implicit smoothing is obtained by constructing implicit lines in the unstructured mesh based on the directions of strong coupling. Both approaches yield large increases in convergence rates over the traditional explicit full-coarsening multigrid algorithm. However, maximum benefits are achieved by combining the two approaches in a coupled manner into a single algorithm. An order of magnitude increase in convergence rate over the traditional explicit full-coarsening algorithm is demonstrated, and convergence rates for high-Reynolds number viscous flows which are independent of the grid aspect ratio are obtained. Further acceleration is provided by incorporating low-Mach-number preconditioning techniques, and a Newton-GMRES strategy which employs the multigrid scheme as a preconditioner. The compounding effects of these various techniques on speed of convergence is documented through several example test cases.

An implementation of a chemical and thermal nonequilibrium flow solver on unstructured meshes and application to blunt bodies

NASA Technical Reports Server (NTRS)

Prabhu, Ramadas K.

1994-01-01

This paper presents a nonequilibrium flow solver, implementation of the algorithm on unstructured meshes, and application to hypersonic flow past blunt bodies. Air is modeled as a mixture of five chemical species, namely O2, N2, O, NO, and N, having two temperatures namely translational and vibrational. The solution algorithm is a cell centered, point implicit upwind scheme that employs Roe's flux difference splitting technique. Implementation of this algorithm on unstructured meshes is described. The computer code is applied to solve Mach 15 flow with and without a Type IV shock interference on a cylindrical body of 2.5mm radius representing a cowl lip. Adaptively generated meshes are employed, and the meshes are refined several times until the solution exhibits detailed flow features and surface pressure and heat flux distributions. Effects of a catalytic wall on surface heat flux distribution are studied. For the Mach 15 Type IV shock interference flow, present results showed a peak heat flux of 544 MW/m2 for a fully catalytic wall and 431 MW/m(exp 2) for a noncatalytic wall. Some of the results are compared with available computational data.

Computing Normal Shock-Isotropic Turbulence Interaction With Tetrahedral Meshes and the Space-Time CESE Method

NASA Astrophysics Data System (ADS)

Venkatachari, Balaji Shankar; Chang, Chau-Lyan

2016-11-01

The focus of this study is scale-resolving simulations of the canonical normal shock- isotropic turbulence interaction using unstructured tetrahedral meshes and the space-time conservation element solution element (CESE) method. Despite decades of development in unstructured mesh methods and its potential benefits of ease of mesh generation around complex geometries and mesh adaptation, direct numerical or large-eddy simulations of turbulent flows are predominantly carried out using structured hexahedral meshes. This is due to the lack of consistent multi-dimensional numerical formulations in conventional schemes for unstructured meshes that can resolve multiple physical scales and flow discontinuities simultaneously. The CESE method - due to its Riemann-solver-free shock capturing capabilities, non-dissipative baseline schemes, and flux conservation in time as well as space - has the potential to accurately simulate turbulent flows using tetrahedral meshes. As part of the study, various regimes of the shock-turbulence interaction (wrinkled and broken shock regimes) will be investigated along with a study on how adaptive refinement of tetrahedral meshes benefits this problem. The research funding for this paper has been provided by Revolutionary Computational Aerosciences (RCA) subproject under the NASA Transformative Aeronautics Concepts Program (TACP).

Mechanism by which DHA inhibits the aggregation of KLVFFA peptides: A molecular dynamics study

NASA Astrophysics Data System (ADS)

Zhou, Hong; Liu, Shengtang; Shao, Qiwen; Ma, Dongfang; Yang, Zaixing; Zhou, Ruhong

2018-03-01

Docosahexaenoic acid (DHA) is one of the omega-3 polyunsaturated fatty acids, which has shown promising applications in lowering Aβ peptide neurotoxicity in vitro by preventing aggregation of Aβ peptides and relieving accumulation of Aβ fibrils. Unfortunately, the underlying molecular mechanisms of how DHA interferes with the aggregation of Aβ peptides remain largely enigmatic. Herein, aggregation behaviors of amyloid-β(Aβ)16-21 peptides (KLVFFA) with or without the presence of a DHA molecule were comparatively studied using extensive all-atom molecular dynamics simulations. We found that DHA could effectively suppress the aggregation of KLVFFA peptides by redirecting peptides to unstructured oligomers. The highly hydrophobic and flexible nature of DHA made it randomly but tightly entangled with Leu-17, Phe-19, and Phe-20 residues to form unstructured but stable complexes. These lower-ordered unstructured oligomers could eventually pass through energy barriers to form ordered β-sheet structures through large conformational fluctuations. This study depicts a microscopic picture for understanding the role and mechanism of DHA in inhibition of aggregation of Aβ peptides, which is generally believed as one of the important pathogenic mechanisms of Alzheimer's disease.

Comparing perceived self-management practices of adult type 2 diabetic patients after completion of a structured ADA certified diabetes self-management education program with unstructured individualized nurse practitioner led diabetes self-management education.

PubMed

Wooley, Dennis S; Kinner, Tracy J

2016-11-01

The purpose was to compare perceived self-management practices of adult type 2 diabetic patients after completing an American Diabetes Association (ADA) certified diabetes self-management education (DSME) program with unstructured individualized nurse practitioner led DSME. Demographic questions and the Self-Care Inventory-Revised (SCIR) were given to two convenience sample patient groups comprising a formal DSME program group and a group within a clinical setting who received informal and unstructured individual education during patient encounters. A t-test was executed between the formal ADA certified education sample and the informal sample's SCI-R individual scores. A second t-test was performed between the two samples' SCI-R mean scores. A t-test determined no statistically significant difference between the formal ADA structured education and informal education samples' SCI-R individual scores. There was not a statistically significant difference between the samples' SCI-R mean scores. The study results suggest that there are not superior DSME settings and instructional approaches. Copyright © 2016 Elsevier Inc. All rights reserved.

Accuracy of an unstructured-grid upwind-Euler algorithm for the ONERA M6 wing

NASA Technical Reports Server (NTRS)

Batina, John T.

1991-01-01

Improved algorithms for the solution of the three-dimensional, time-dependent Euler equations are presented for aerodynamic analysis involving unstructured dynamic meshes. The improvements have been developed recently to the spatial and temporal discretizations used by unstructured-grid flow solvers. The spatial discretization involves a flux-split approach that is naturally dissipative and captures shock waves sharply with at most one grid point within the shock structure. The temporal discretization involves either an explicit time-integration scheme using a multistage Runge-Kutta procedure or an implicit time-integration scheme using a Gauss-Seidel relaxation procedure, which is computationally efficient for either steady or unsteady flow problems. With the implicit Gauss-Seidel procedure, very large time steps may be used for rapid convergence to steady state, and the step size for unsteady cases may be selected for temporal accuracy rather than for numerical stability. Steady flow results are presented for both the NACA 0012 airfoil and the Office National d'Etudes et de Recherches Aerospatiales M6 wing to demonstrate applications of the new Euler solvers. The paper presents a description of the Euler solvers along with results and comparisons that assess the capability.

Unstructured LES of Reacting Multiphase Flows in Realistic Gas Turbine Combustors

NASA Technical Reports Server (NTRS)

Ham, Frank; Apte, Sourabh; Iaccarino, Gianluca; Wu, Xiao-Hua; Herrmann, Marcus; Constantinescu, George; Mahesh, Krishnan; Moin, Parviz

2003-01-01

As part of the Accelerated Strategic Computing Initiative (ASCI) program, an accurate and robust simulation tool is being developed to perform high-fidelity LES studies of multiphase, multiscale turbulent reacting flows in aircraft gas turbine combustor configurations using hybrid unstructured grids. In the combustor, pressurized gas from the upstream compressor is reacted with atomized liquid fuel to produce the combustion products that drive the downstream turbine. The Large Eddy Simulation (LES) approach is used to simulate the combustor because of its demonstrated superiority over RANS in predicting turbulent mixing, which is central to combustion. This paper summarizes the accomplishments of the combustor group over the past year, concentrating mainly on the two major milestones achieved this year: 1) Large scale simulation: A major rewrite and redesign of the flagship unstructured LES code has allowed the group to perform large eddy simulations of the complete combustor geometry (all 18 injectors) with over 100 million control volumes; 2) Multi-physics simulation in complex geometry: The first multi-physics simulations including fuel spray breakup, coalescence, evaporation, and combustion are now being performed in a single periodic sector (1/18th) of an actual Pratt & Whitney combustor geometry.

Implicit flux-split Euler schemes for unsteady aerodynamic analysis involving unstructured dynamic meshes

NASA Technical Reports Server (NTRS)

Batina, John T.

1990-01-01

Improved algorithm for the solution of the time-dependent Euler equations are presented for unsteady aerodynamic analysis involving unstructured dynamic meshes. The improvements were developed recently to the spatial and temporal discretizations used by unstructured grid flow solvers. The spatial discretization involves a flux-split approach which is naturally dissipative and captures shock waves sharply with at most one grid point within the shock structure. The temporal discretization involves an implicit time-integration scheme using a Gauss-Seidel relaxation procedure which is computationally efficient for either steady or unsteady flow problems. For example, very large time steps may be used for rapid convergence to steady state, and the step size for unsteady cases may be selected for temporal accuracy rather than for numerical stability. Steady and unsteady flow results are presented for the NACA 0012 airfoil to demonstrate applications of the new Euler solvers. The unsteady results were obtained for the airfoil pitching harmonically about the quarter chord. The resulting instantaneous pressure distributions and lift and moment coefficients during a cycle of motion compare well with experimental data. A description of the Euler solvers is presented along with results and comparisons which assess the capability.

Design and fabrication of robotic gripper for grasping in minimizing contact force

NASA Astrophysics Data System (ADS)

Heidari, Hamidreza; Pouria, Milad Jafary; Sharifi, Shahriar; Karami, Mahmoudreza

2018-03-01

This paper presents a new method to improve the kinematics of robot gripper for grasping in unstructured environments, such as space operations. The robot gripper is inspired from the human hand and kept the hand design close to the structure of human fingers to provide successful grasping capabilities. The main goal is to improve kinematic structure of gripper to increase the grasping capability of large objects, decrease the contact forces and makes a successful grasp of various objects in unstructured environments. This research will describe the development of a self-adaptive and reconfigurable robotic hand for space operations through mechanical compliance which is versatile, robust and easy to control. Our model contains two fingers, two-link and three-link, with combining a kinematic model of thumb index. Moreover, some experimental tests are performed to examine the effectiveness of the hand-made in real, unstructured tasks. The results represent that the successful grasp range is improved about 30% and the contact forces is reduced approximately 10% for a wide range of target object size. According to the obtained results, the proposed approach provides an accommodative kinematic model which makes the better grasping capability by fingers geometries for a robot gripper.

On Multi-Dimensional Unstructured Mesh Adaption

NASA Technical Reports Server (NTRS)

Wood, William A.; Kleb, William L.

1999-01-01

Anisotropic unstructured mesh adaption is developed for a truly multi-dimensional upwind fluctuation splitting scheme, as applied to scalar advection-diffusion. The adaption is performed locally using edge swapping, point insertion/deletion, and nodal displacements. Comparisons are made versus the current state of the art for aggressive anisotropic unstructured adaption, which is based on a posteriori error estimates. Demonstration of both schemes to model problems, with features representative of compressible gas dynamics, show the present method to be superior to the a posteriori adaption for linear advection. The performance of the two methods is more similar when applied to nonlinear advection, with a difference in the treatment of shocks. The a posteriori adaption can excessively cluster points to a shock, while the present multi-dimensional scheme tends to merely align with a shock, using fewer nodes. As a consequence of this alignment tendency, an implementation of eigenvalue limiting for the suppression of expansion shocks is developed for the multi-dimensional distribution scheme. The differences in the treatment of shocks by the adaption schemes, along with the inherently low levels of artificial dissipation in the fluctuation splitting solver, suggest the present method is a strong candidate for applications to compressible gas dynamics.

A comparison of a child’s fundamental frequencies in structured elicited vocalizations versus unstructured natural vocalizations: A case study

PubMed Central

Hunter, Eric J.

2009-01-01

Objectives Building on the concept that task type may influence fundamental frequency (F0) values, the purpose of this case study was to investigate the difference in a child’s F0 during structured, elicited tasks and long-term, unstructured activities. It also explores the possibility that the distribution in children’s F0 may make the standard statistical measures of mean and standard deviation less than ideal metrics. Methods A healthy male child (5 years, 7 months) was evaluated. The child completed four voice tasks used in a previous study of the influence of task type on F0 values: (1) sustaining the vowel /a/; (2) sustaining the vowel, /a/, embedded in a word at the end of a phrase; (3) repeating a sentence; and (4) counting from 1 to 10. The child also wore a National Center for Voice and Speech voice dosimeter, a device that collects voice data over the course of an entire day, during all activities for 34 hours over 4 days. Results Throughout the structured vocal tasks within the clinical environment, the child’s F0, as measured by both the dosimeter and acoustic analysis of microphone data, was similar for all four tasks, with the counting task the most dissimilar. The mean F0 (~257 Hz) matched very closely to the average task results in the literature given for the child’s age group. However, the child’s mean fundamental frequency during the unstructured activities was significantly higher (~376 Hz). Finally, the mode and median of the structured vocal tasks were respectively 260 Hz and 259 Hz (both near the mean), while the unstructured mode and median were respectively 290 Hz and 355 Hz. Conclusions The results of this study suggest that children may produce a notably different voice pattern during clinical observations compared to routine daily activities. In addition, the child’s long-term F0 distribution is not normal. If this distribution is consistent in long-term, unstructured natural vocalization patterns of children, statistical mean would not be a valid measure. Mode and median are suggested as two parameters which convey more accurate information about typical F0 usage. Finally, future research avenues, including further exploration of how children may adapt their F0 to various environments, conversation partners, and activity, are suggested. PMID:19185926

The nucleoid protein Dps binds genomic DNA of Escherichia coli in a non-random manner

PubMed Central

Kondrashov, F. A.; Toshchakov, S. V.; Dominova, I.; Shvyreva, U. S.; Vrublevskaya, V. V.; Morenkov, O. S.; Panyukov, V. V.

2017-01-01

Dps is a multifunctional homododecameric protein that oxidizes Fe2+ ions accumulating them in the form of Fe2O3 within its protein cavity, interacts with DNA tightly condensing bacterial nucleoid upon starvation and performs some other functions. During the last two decades from discovery of this protein, its ferroxidase activity became rather well studied, but the mechanism of Dps interaction with DNA still remains enigmatic. The crucial role of lysine residues in the unstructured N-terminal tails led to the conventional point of view that Dps binds DNA without sequence or structural specificity. However, deletion of dps changed the profile of proteins in starved cells, SELEX screen revealed genomic regions preferentially bound in vitro and certain affinity of Dps for artificial branched molecules was detected by atomic force microscopy. Here we report a non-random distribution of Dps binding sites across the bacterial chromosome in exponentially growing cells and show their enrichment with inverted repeats prone to form secondary structures. We found that the Dps-bound regions overlap with sites occupied by other nucleoid proteins, and contain overrepresented motifs typical for their consensus sequences. Of the two types of genomic domains with extensive protein occupancy, which can be highly expressed or transcriptionally silent only those that are enriched with RNA polymerase molecules were preferentially occupied by Dps. In the dps-null mutant we, therefore, observed a differentially altered expression of several targeted genes and found suppressed transcription from the dps promoter. In most cases this can be explained by the relieved interference with Dps for nucleoid proteins exploiting sequence-specific modes of DNA binding. Thus, protecting bacterial cells from different stresses during exponential growth, Dps can modulate transcriptional integrity of the bacterial chromosome hampering RNA biosynthesis from some genes via competition with RNA polymerase or, vice versa, competing with inhibitors to activate transcription. PMID:28800583

Nuclear factor 90 uses an ADAR2-like binding mode to recognize specific bases in dsRNA.

PubMed

Jayachandran, Uma; Grey, Heather; Cook, Atlanta G

2016-02-29

Nuclear factors 90 and 45 (NF90 and NF45) form a protein complex involved in the post-transcriptional control of many genes in vertebrates. NF90 is a member of the dsRNA binding domain (dsRBD) family of proteins. RNA binding partners identified so far include elements in 3' untranslated regions of specific mRNAs and several non-coding RNAs. In NF90, a tandem pair of dsRBDs separated by a natively unstructured segment confers dsRNA binding activity. We determined a crystal structure of the tandem dsRBDs of NF90 in complex with a synthetic dsRNA. This complex shows surprising similarity to the tandem dsRBDs from an adenosine-to-inosine editing enzyme, ADAR2 in complex with a substrate RNA. Residues involved in unusual base-specific recognition in the minor groove of dsRNA are conserved between NF90 and ADAR2. These data suggest that, like ADAR2, underlying sequences in dsRNA may influence how NF90 recognizes its target RNAs. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Transient α-helices in the disordered RPEL motifs of the serum response factor coactivator MKL1

NASA Astrophysics Data System (ADS)

Mizuguchi, Mineyuki; Fuju, Takahiro; Obita, Takayuki; Ishikawa, Mitsuru; Tsuda, Masaaki; Tabuchi, Akiko

2014-06-01

The megakaryoblastic leukemia 1 (MKL1) protein functions as a transcriptional coactivator of the serum response factor. MKL1 has three RPEL motifs (RPEL1, RPEL2, and RPEL3) in its N-terminal region. MKL1 binds to monomeric G-actin through RPEL motifs, and the dissociation of MKL1 from G-actin promotes the translocation of MKL1 to the nucleus. Although structural data are available for RPEL motifs of MKL1 in complex with G-actin, the structural characteristics of RPEL motifs in the free state have been poorly defined. Here we characterized the structures of free RPEL motifs using NMR and CD spectroscopy. NMR and CD measurements showed that free RPEL motifs are largely unstructured in solution. However, NMR analysis identified transient α-helices in the regions where helices α1 and α2 are induced upon binding to G-actin. Proline mutagenesis showed that the transient α-helices are locally formed without helix-helix interactions. The helix content is higher in the order of RPEL1, RPEL2, and RPEL3. The amount of preformed structure may correlate with the binding affinity between the intrinsically disordered protein and its target molecule.

A rule-based named-entity recognition method for knowledge extraction of evidence-based dietary recommendations

PubMed Central

2017-01-01

Evidence-based dietary information represented as unstructured text is a crucial information that needs to be accessed in order to help dietitians follow the new knowledge arrives daily with newly published scientific reports. Different named-entity recognition (NER) methods have been introduced previously to extract useful information from the biomedical literature. They are focused on, for example extracting gene mentions, proteins mentions, relationships between genes and proteins, chemical concepts and relationships between drugs and diseases. In this paper, we present a novel NER method, called drNER, for knowledge extraction of evidence-based dietary information. To the best of our knowledge this is the first attempt at extracting dietary concepts. DrNER is a rule-based NER that consists of two phases. The first one involves the detection and determination of the entities mention, and the second one involves the selection and extraction of the entities. We evaluate the method by using text corpora from heterogeneous sources, including text from several scientifically validated web sites and text from scientific publications. Evaluation of the method showed that drNER gives good results and can be used for knowledge extraction of evidence-based dietary recommendations. PMID:28644863

Free-energy landscape of intrinsically disordered proteins investigated by all-atom multicanonical molecular dynamics.

PubMed

Higo, Junichi; Umezawa, Koji

2014-01-01

We introduce computational studies on intrinsically disordered proteins (IDPs). Especially, we present our multicanonical molecular dynamics (McMD) simulations of two IDP-partner systems: NRSF-mSin3 and pKID-KIX. McMD is one of enhanced conformational sampling methods useful for conformational sampling of biomolecular systems. IDP adopts a specific tertiary structure upon binding to its partner molecule, although it is unstructured in the unbound state (i.e. the free state). This IDP-specific property is called "coupled folding and binding". The McMD simulation treats the biomolecules with an all-atom model immersed in an explicit solvent. In the initial configuration of simulation, IDP and its partner molecules are set to be distant from each other, and the IDP conformation is disordered. The computationally obtained free-energy landscape for coupled folding and binding has shown that native- and non-native-complex clusters distribute complicatedly in the conformational space. The all-atom simulation suggests that both of induced-folding and population-selection are coupled complicatedly in the coupled folding and binding. Further analyses have exemplified that the conformational fluctuations (dynamical flexibility) in the bound and unbound states are essentially important to characterize IDP functioning.

SSMART: Sequence-structure motif identification for RNA-binding proteins.

PubMed

Munteanu, Alina; Mukherjee, Neelanjan; Ohler, Uwe

2018-06-11

RNA-binding proteins (RBPs) regulate every aspect of RNA metabolism and function. There are hundreds of RBPs encoded in the eukaryotic genomes, and each recognize its RNA targets through a specific mixture of RNA sequence and structure properties. For most RBPs, however, only a primary sequence motif has been determined, while the structure of the binding sites is uncharacterized. We developed SSMART, an RNA motif finder that simultaneously models the primary sequence and the structural properties of the RNA targets sites. The sequence-structure motifs are represented as consensus strings over a degenerate alphabet, extending the IUPAC codes for nucleotides to account for secondary structure preferences. Evaluation on synthetic data showed that SSMART is able to recover both sequence and structure motifs implanted into 3'UTR-like sequences, for various degrees of structured/unstructured binding sites. In addition, we successfully used SSMART on high-throughput in vivo and in vitro data, showing that we not only recover the known sequence motif, but also gain insight into the structural preferences of the RBP. Availability: SSMART is freely available at https://ohlerlab.mdc-berlin.de/software/SSMART_137/. Supplementary data are available at Bioinformatics online.

The outer-membrane export signal of Porphyromonas gingivalis type IX secretion system (T9SS) is a conserved C-terminal β-sandwich domain

PubMed Central

de Diego, Iñaki; Ksiazek, Miroslaw; Mizgalska, Danuta; Koneru, Lahari; Golik, Przemyslaw; Szmigielski, Borys; Nowak, Magdalena; Nowakowska, Zuzanna; Potempa, Barbara; Houston, John A.; Enghild, Jan J.; Thøgersen, Ida B.; Gao, Jinlong; Kwan, Ann H.; Trewhella, Jill; Dubin, Grzegorz; Gomis-Rüth, F. Xavier; Nguyen, Ky-Anh; Potempa, Jan

2016-01-01

In the recently characterized Type IX Secretion System (T9SS), the conserved C-terminal domain (CTD) in secreted proteins functions as an outer membrane translocation signal for export of virulence factors to the cell surface in the Gram-negative Bacteroidetes phylum. In the periodontal pathogen Porphyromonas gingivalis, the CTD is cleaved off by PorU sortase in a sequence-independent manner, and anionic lipopolysaccharide (A-LPS) is attached to many translocated proteins, thus anchoring them to the bacterial surface. Here, we solved the atomic structure of the CTD of gingipain B (RgpB) from P. gingivalis, alone and together with a preceding immunoglobulin-superfamily domain (IgSF). The CTD was found to possess a typical Ig-like fold encompassing seven antiparallel β-strands organized in two β-sheets, packed into a β-sandwich structure that can spontaneously dimerise through C-terminal strand swapping. Small angle X-ray scattering (SAXS) revealed no fixed orientation of the CTD with respect to the IgSF. By introducing insertion or substitution of residues within the inter-domain linker in the native protein, we were able to show that despite the region being unstructured, it nevertheless is resistant to general proteolysis. These data suggest structural motifs located in the two adjacent Ig-like domains dictate the processing of CTDs by the T9SS secretion pathway. PMID:27005013

The role of conformational selection in the molecular recognition of the wild type and mutants XPA67-80 peptides by ERCC1.

PubMed

Fadda, Elisa

2015-07-01

Molecular recognition is a fundamental step in the coordination of biomolecular pathways. Understanding how recognition and binding occur between highly flexible protein domains is a complex task. The conformational selection theory provides an elegant rationalization of the recognition mechanism, especially valid in cases when unstructured protein regions are involved. The recognition of a poorly structured peptide, namely XPA67-80 , by its target receptor ERCC1, falls in this challenging study category. The microsecond molecular dynamics (MD) simulations, discussed in this work, show that the conformational propensity of the wild type XPA67-80 peptide in solution supports conformational selection as the key mechanism driving its molecular recognition by ERCC1. Moreover, all the mutations of the XPA67-80 peptide studied here cause a significant increase of its conformational disorder, relative to the wild type. Comparison to experimental data suggests that the loss of the recognized structural motifs at the microscopic time scale can contribute to the critical decrease in binding observed for one of the mutants, further substantiating the key role of conformational selection in recognition. Ultimately, because of the high sequence identity and analogy in binding, it is conceivable that the conclusions of this study on the XPA67-80 peptide also apply to the ERCC1-binding domain of the XPA protein. © 2015 Wiley Periodicals, Inc.

A Fluorescent Protein Scaffold for Presenting Structurally Constrained Peptides Provides an Effective Screening System to Identify High Affinity Target-Binding Peptides

PubMed Central

Kadonosono, Tetsuya; Yabe, Etsuri; Furuta, Tadaomi; Yamano, Akihiro; Tsubaki, Takuya; Sekine, Takuya; Kuchimaru, Takahiro; Sakurai, Minoru; Kizaka-Kondoh, Shinae

2014-01-01

Peptides that have high affinity for target molecules on the surface of cancer cells are crucial for the development of targeted cancer therapies. However, unstructured peptides often fail to bind their target molecules with high affinity. To efficiently identify high-affinity target-binding peptides, we have constructed a fluorescent protein scaffold, designated gFPS, in which structurally constrained peptides are integrated at residues K131–L137 of superfolder green fluorescent protein. Molecular dynamics simulation supported the suitability of this site for presentation of exogenous peptides with a constrained structure. gFPS can present 4 to 12 exogenous amino acids without a loss of fluorescence. When gFPSs presenting human epidermal growth factor receptor type 2 (HER2)-targeting peptides were added to the culture medium of HER2-expressing cells, we could easily identify the peptides with high HER2-affinity and -specificity based on gFPS fluorescence. In addition, gFPS could be expressed on the yeast cell surface and applied for a high-throughput screening. These results demonstrate that gFPS has the potential to serve as a powerful tool to improve screening of structurally constrained peptides that have a high target affinity, and suggest that it could expedite the one-step identification of clinically applicable cancer cell-binding peptides. PMID:25084350

Structure and interactions of biological helices

NASA Astrophysics Data System (ADS)

Kornyshev, Alexei A.; Lee, Dominic J.; Leikin, Sergey; Wynveen, Aaron

2007-07-01

Helices are essential building blocks of living organisms, be they molecular fragments of proteins ( α -helices), macromolecules (DNA and collagen), or multimolecular assemblies (microtubules and viruses). Their interactions are involved in packing of meters of genetic material within cells and phage heads, recognition of homologous genes in recombination and DNA repair, stability of tissues, and many other processes. Helical molecules form a variety of mesophases in vivo and in vitro. Recent structural studies, direct measurements of intermolecular forces, single-molecule manipulations, and other experiments have accumulated a wealth of information and revealed many puzzling physical phenomena. It is becoming increasingly clear that in many cases the physics of biological helices cannot be described by theories that treat them as simple, unstructured polyelectrolytes. The present article focuses on the most important and interesting aspects of the physics of structured macromolecules, highlighting various manifestations of the helical motif in their structure, elasticity, interactions with counterions, aggregation, and poly- and mesomorphic transitions.

Epigallocatechin-3-gallate preferentially induces aggregation of amyloidogenic immunoglobulin light chains

PubMed Central

Hora, Manuel; Carballo-Pacheco, Martin; Weber, Benedikt; Morris, Vanessa K.; Wittkopf, Antje; Buchner, Johannes; Strodel, Birgit; Reif, Bernd

2017-01-01

Antibody light chain amyloidosis is a rare disease caused by fibril formation of secreted immunoglobulin light chains (LCs). The huge variety of antibody sequences puts a serious challenge to drug discovery. The green tea polyphenol epigallocatechin-3-gallate (EGCG) is known to interfere with fibril formation in general. Here we present solution- and solid-state NMR studies as well as MD simulations to characterise the interaction of EGCG with LC variable domains. We identified two distinct EGCG binding sites, both of which include a proline as an important recognition element. The binding sites were confirmed by site-directed mutagenesis and solid-state NMR analysis. The EGCG-induced protein complexes are unstructured. We propose a general mechanistic model for EGCG binding to a conserved site in LCs. We find that EGCG reacts selectively with amyloidogenic mutants. This makes this compound a promising lead structure, that can handle the immense sequence variability of antibody LCs. PMID:28128355

The DEAD-Box Protein CYT-19 Uses Arginine Residues in Its C-Tail To Tether RNA Substrates.

PubMed

Busa, Veronica F; Rector, Maxwell J; Russell, Rick

2017-07-18

DEAD-box proteins are nonprocessive RNA helicases that play diverse roles in cellular processes. The Neurospora crassa DEAD-box protein CYT-19 promotes mitochondrial group I intron splicing and functions as a general RNA chaperone. CYT-19 includes a disordered, arginine-rich "C-tail" that binds RNA, positioning the helicase core to capture and unwind nearby RNA helices. Here we probed the C-tail further by varying the number and positions of arginines within it. We found that removing sets of as few as four of the 11 arginines reduced RNA unwinding activity (k cat /K M ) to a degree equivalent to that seen upon removal of the C-tail, suggesting that a minimum or "threshold" number of arginines is required. In addition, a mutant with 16 arginines displayed RNA unwinding activity greater than that of wild-type CYT-19. The C-tail modifications impacted unwinding only of RNA helices within constructs that included an adjacent helix or structured RNA element that would allow C-tail binding, indicating that the helicase core remained active in the mutants. In addition, changes in RNA unwinding efficiency of the mutants were mirrored by changes in functional RNA affinity, as determined from the RNA concentration dependence of ATPase activity, suggesting that the C-tail functions primarily to increase RNA affinity. Interestingly, the salt concentration dependence of RNA unwinding activity is unaffected by C-tail composition, suggesting that the C-tail uses primarily hydrogen bonding, not electrostatic interactions, to bind double-stranded RNA. Our results provide insights into how an unstructured C-tail contributes to DEAD-box protein activity and suggest parallels with other families of RNA- and DNA-binding proteins.

NMR investigations of the dual targeting peptide of Thr-tRNA synthetase and its interaction with the mitochondrial Tom20 receptor in Arabidopsis thaliana.

PubMed

Ye, Weihua; Spånning, Erika; Unnerståle, Sofia; Gotthold, David; Glaser, Elzbieta; Mäler, Lena

2012-10-01

Most mitochondrial proteins are synthesized in the cytosol as precursor proteins containing an N-terminal targeting peptide and are imported into mitochondria through the import machineries, the translocase of the outer mitochondrial membrane (TOM) and the translocase of the inner mitochondrial membrane (TIM). The N-terminal targeting peptide of precursor proteins destined for the mitochondrial matrix is recognized by the Tom20 receptor and plays an important role in the import process. Protein import is usually organelle specific, but several plant proteins are dually targeted into mitochondria and chloroplasts using an ambiguous dual targeting peptide. We present NMR studies of the dual targeting peptide of Thr-tRNA synthetase and its interaction with Tom20 in Arabidopsis thaliana. Our findings show that the targeting peptide is mostly unstructured in buffer, with a propensity to form α-helical structure in one region, S6-F27, and a very weak β-strand propensity for Q34-Q38. The α-helical structured region has an amphiphilic character and a φχχφφ motif, both of which have previously been shown to be important for mitochondrial import. Using NMR we have mapped out two regions in the peptide that are important for Tom20 recognition: one of them, F9-V28, overlaps with the amphiphilic region, and the other comprises residues L30-Q39. Our results show that the targeting peptide may interact with Tom20 in several ways. Furthermore, our results indicate a weak, dynamic interaction. The results provide for the first time molecular details on the interaction of the Tom20 receptor with a dual targeting peptide. © 2012 The Authors Journal compilation © 2012 FEBS.

New insights into flavivirus biology: the influence of pH over interactions between prM and E proteins

NASA Astrophysics Data System (ADS)

Oliveira, Edson R. A.; de Alencastro, Ricardo B.; Horta, Bruno A. C.

2017-11-01

Diseases caused by flaviviruses, such as dengue and zika, are globally recognized as major threats. During infection, a critical point in their replicative cycle is the maturation step, which occurs throughout the cellular exocytic pathway. This step is a pH-dependent process that involves the modification of the viral envelope by converting prM (pre-membrane) into M (membrane) proteins with the release of a "pr peptide". After this reaction, the pr peptides remain bound to the viral envelope while the virions cross the acidic trans-Golgi network, and are released only at neutral pH after secretion of the virus particles. Despite this current knowledge, the molecular basis of the flavivirus maturation step is largely unknown. Here, based on the crystal structure of the dengue pr-E complex ("pr peptide" bound to virus envelope protein) and using molecular dynamics simulations, we found that the pH shift from acidic to neutral yields considerable structural changes in the system. Dynamic cross correlation maps and root mean square deviation analyses revealed that the pr-E junction is clearly unstable under neutral pH. Secondary structure analysis also revealed that the fusion loop region, present in the E protein, is sensitive to pH and tends to unstructure at a neutral environment. Moreover, we found that five residues present in the E protein, Gly102, His244, Thr70, Thr68 and Asn67 are critical to confer stability to the pr-E complex while inside the Golgi apparatus. This work brings details about the dynamical behavior of the pr-E system, helps to better understand the flavivirus biology and may also be of use in the development of novel antiviral strategies.

Role of the C-terminal extensions of alpha-crystallins. Swapping the C-terminal extension of alpha-crystallin to alphaB-crystallin results in enhanced chaperone activity.

PubMed

Pasta, Saloni Yatin; Raman, Bakthisaran; Ramakrishna, Tangirala; Rao, Ch Mohan

2002-11-29

Several small heat shock proteins contain a well conserved alpha-crystallin domain, flanked by an N-terminal domain and a C-terminal extension, both of which vary in length and sequence. The structural and functional role of the C-terminal extension of small heat shock proteins, particularly of alphaA- and alphaB-crystallins, is not well understood. We have swapped the C-terminal extensions between alphaA- and alphaB-crystallins and generated two novel chimeric proteins, alphaABc and alphaBAc. We have investigated the domain-swapped chimeras for structural and functional alterations. We have used thermal and non-thermal models of protein aggregation and found that the chimeric alphaB with the C-terminal extension of alphaA-crystallin, alphaBAc, exhibits dramatically enhanced chaperone-like activity. Interestingly, however, the chimeric alphaA with the C-terminal extension of alphaB-crystallin, alphaABc, has almost lost its activity. Pyrene solubilization and bis-1-anilino-8-naphthalenesulfonate binding studies show that alphaBAc exhibits more solvent-exposed hydrophobic pockets than alphaA, alphaB, or alphaABc. Significant tertiary structural changes are revealed by tryptophan fluorescence and near-UV CD studies upon swapping the C-terminal extensions. The far-UV CD spectrum of alphaBAc differs from that of alphaB-crystallin whereas that of alphaABc overlaps with that of alphaA-crystallin. Gel filtration chromatography shows alteration in the size of the proteins upon swapping the C-terminal extensions. Our study demonstrates that the unstructured C-terminal extensions play a crucial role in the structure and chaperone activity, in addition to generally believed electrostatic "solubilizer" function.

A Fast and Robust Poisson-Boltzmann Solver Based on Adaptive Cartesian Grids

PubMed Central

Boschitsch, Alexander H.; Fenley, Marcia O.

2011-01-01

An adaptive Cartesian grid (ACG) concept is presented for the fast and robust numerical solution of the 3D Poisson-Boltzmann Equation (PBE) governing the electrostatic interactions of large-scale biomolecules and highly charged multi-biomolecular assemblies such as ribosomes and viruses. The ACG offers numerous advantages over competing grid topologies such as regular 3D lattices and unstructured grids. For very large biological molecules and multi-biomolecule assemblies, the total number of grid-points is several orders of magnitude less than that required in a conventional lattice grid used in the current PBE solvers thus allowing the end user to obtain accurate and stable nonlinear PBE solutions on a desktop computer. Compared to tetrahedral-based unstructured grids, ACG offers a simpler hierarchical grid structure, which is naturally suited to multigrid, relieves indirect addressing requirements and uses fewer neighboring nodes in the finite difference stencils. Construction of the ACG and determination of the dielectric/ionic maps are straightforward, fast and require minimal user intervention. Charge singularities are eliminated by reformulating the problem to produce the reaction field potential in the molecular interior and the total electrostatic potential in the exterior ionic solvent region. This approach minimizes grid-dependency and alleviates the need for fine grid spacing near atomic charge sites. The technical portion of this paper contains three parts. First, the ACG and its construction for general biomolecular geometries are described. Next, a discrete approximation to the PBE upon this mesh is derived. Finally, the overall solution procedure and multigrid implementation are summarized. Results obtained with the ACG-based PBE solver are presented for: (i) a low dielectric spherical cavity, containing interior point charges, embedded in a high dielectric ionic solvent – analytical solutions are available for this case, thus allowing rigorous assessment of the solution accuracy; (ii) a pair of low dielectric charged spheres embedded in a ionic solvent to compute electrostatic interaction free energies as a function of the distance between sphere centers; (iii) surface potentials of proteins, nucleic acids and their larger-scale assemblies such as ribosomes; and (iv) electrostatic solvation free energies and their salt sensitivities – obtained with both linear and nonlinear Poisson-Boltzmann equation – for a large set of proteins. These latter results along with timings can serve as benchmarks for comparing the performance of different PBE solvers. PMID:21984876

Human polyhomeotic homolog 3 (PHC3) sterile alpha motif (SAM) linker allows open-ended polymerization of PHC3 SAM.

PubMed

Robinson, Angela K; Leal, Belinda Z; Nanyes, David R; Kaur, Yogeet; Ilangovan, Udayar; Schirf, Virgil; Hinck, Andrew P; Demeler, Borries; Kim, Chongwoo A

2012-07-10

Sterile alpha motifs (SAMs) are frequently found in eukaryotic genomes. An intriguing property of many SAMs is their ability to self-associate, forming an open-ended polymer structure whose formation has been shown to be essential for the function of the protein. What remains largely unresolved is how polymerization is controlled. Previously, we had determined that the stretch of unstructured residues N-terminal to the SAM of a Drosophila protein called polyhomeotic (Ph), a member of the polycomb group (PcG) of gene silencers, plays a key role in controlling Ph SAM polymerization. Ph SAM with its native linker created shorter polymers compared to Ph SAM attached to either a random linker or no linker. Here, we show that the SAM linker for the human Ph ortholog, polyhomeotic homolog 3 (PHC3), also controls PHC3 SAM polymerization but does so in the opposite fashion. PHC3 SAM with its native linker allows longer polymers to form compared to when attached to a random linker. Attaching the PHC3 SAM linker to Ph SAM also resulted in extending Ph SAM polymerization. Moreover, in the context of full-length Ph protein, replacing the SAM linker with PHC3 SAM linker, intended to create longer polymers, resulted in greater repressive ability for the chimera compared to wild-type Ph. These findings show that polymeric SAM linkers evolved to modulate a wide dynamic range of SAM polymerization abilities and suggest that rationally manipulating the function of SAM containing proteins through controlling their SAM polymerization may be possible.

Oligomerisation of Synaptobrevin-2 Studied by Native Mass Spectrometry and Chemical Cross-Linking

NASA Astrophysics Data System (ADS)

Wittig, Sabine; Haupt, Caroline; Hoffmann, Waldemar; Kostmann, Susann; Pagel, Kevin; Schmidt, Carla

2018-06-01

Synaptobrevin-2 is a key player in signal transmission in neurons. It forms, together with SNAP25 and Syntaxin-1A, the neuronal soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex and mediates exocytosis of synaptic vesicles with the pre-synaptic membrane. While Synaptobrevin-2 is part of a four-helix bundle in this SNARE complex, it is natively unstructured in the absence of lipids or other SNARE proteins. Partially folded segments, presumably SNARE complex formation intermediates, as well as formation of Synaptobrevin-2 dimers and oligomers, were identified in previous studies. Here, we employ three Synaptobrevin-2 variants—the full-length protein Syb(1-116), the soluble, cytosolic variant Syb(1-96) as well as a shorter version Syb(49-96) containing structured segments but omitting a trigger site for SNARE complex formation—to study oligomerisation in the absence of interaction partners or when incorporated into the lipid bilayer of liposomes. Combining native mass spectrometry with chemical cross-linking, we find that the truncated versions show increased oligomerisation. Our findings from both techniques agree well and confirm the presence of oligomers in solution while membrane-bound Synaptobrevin-2 is mostly monomeric. Using ion mobility mass spectrometry, we could further show that lower charge states of Syb(49-96) oligomers, which most likely represent solution structures, follow an isotropic growth curve suggesting that they are intrinsically disordered. From a technical point of view, we show that the combination of native ion mobility mass spectrometry with chemical cross-linking is well-suited for the analysis of protein homo-oligomers. [Figure not available: see fulltext.

Mutation of CD2AP and SH3KBP1 Binding Motif in Alphavirus nsP3 Hypervariable Domain Results in Attenuated Virus.

PubMed

Mutso, Margit; Morro, Ainhoa Moliner; Smedberg, Cecilia; Kasvandik, Sergo; Aquilimeba, Muriel; Teppor, Mona; Tarve, Liisi; Lulla, Aleksei; Lulla, Valeria; Saul, Sirle; Thaa, Bastian; McInerney, Gerald M; Merits, Andres; Varjak, Margus

2018-04-27

Infection by Chikungunya virus (CHIKV) of the Old World alphaviruses (family Togaviridae) in humans can cause arthritis and arthralgia. The virus encodes four non-structural proteins (nsP) (nsP1, nsp2, nsP3 and nsP4) that act as subunits of the virus replicase. These proteins also interact with numerous host proteins and some crucial interactions are mediated by the unstructured C-terminal hypervariable domain (HVD) of nsP3. In this study, a human cell line expressing EGFP tagged with CHIKV nsP3 HVD was established. Using quantitative proteomics, it was found that CHIKV nsP3 HVD can bind cytoskeletal proteins, including CD2AP, SH3KBP1, CAPZA1, CAPZA2 and CAPZB. The interaction with CD2AP was found to be most evident; its binding site was mapped to the second SH3 ligand-like element in nsP3 HVD. Further assessment indicated that CD2AP can bind to nsP3 HVDs of many different New and Old World alphaviruses. Mutation of the short binding element hampered the ability of the virus to establish infection. The mutation also abolished ability of CD2AP to co-localise with nsP3 and replication complexes of CHIKV; the same was observed for Semliki Forest virus (SFV) harbouring a similar mutation. Similar to CD2AP, its homolog SH3KBP1 also bound the identified motif in CHIKV and SFV nsP3.

Filling the gaps between tools and users: a tool comparator, using protein-protein interaction as an example.

PubMed

Kano, Yoshinobu; Nguyen, Ngan; Saetre, Rune; Yoshida, Kazuhiro; Miyao, Yusuke; Tsuruoka, Yoshimasa; Matsubayashi, Yuichiro; Ananiadou, Sophia; Tsujii, Jun'ichi

2008-01-01

Recently, several text mining programs have reached a near-practical level of performance. Some systems are already being used by biologists and database curators. However, it has also been recognized that current Natural Language Processing (NLP) and Text Mining (TM) technology is not easy to deploy, since research groups tend to develop systems that cater specifically to their own requirements. One of the major reasons for the difficulty of deployment of NLP/TM technology is that re-usability and interoperability of software tools are typically not considered during development. While some effort has been invested in making interoperable NLP/TM toolkits, the developers of end-to-end systems still often struggle to reuse NLP/TM tools, and often opt to develop similar programs from scratch instead. This is particularly the case in BioNLP, since the requirements of biologists are so diverse that NLP tools have to be adapted and re-organized in a much more extensive manner than was originally expected. Although generic frameworks like UIMA (Unstructured Information Management Architecture) provide promising ways to solve this problem, the solution that they provide is only partial. In order for truly interoperable toolkits to become a reality, we also need sharable type systems and a developer-friendly environment for software integration that includes functionality for systematic comparisons of available tools, a simple I/O interface, and visualization tools. In this paper, we describe such an environment that was developed based on UIMA, and we show its feasibility through our experience in developing a protein-protein interaction (PPI) extraction system.

Data Integration for Heterogenous Datasets

PubMed Central

2014-01-01

Abstract More and more, the needs of data analysts are requiring the use of data outside the control of their own organizations. The increasing amount of data available on the Web, the new technologies for linking data across datasets, and the increasing need to integrate structured and unstructured data are all driving this trend. In this article, we provide a technical overview of the emerging “broad data” area, in which the variety of heterogeneous data being used, rather than the scale of the data being analyzed, is the limiting factor in data analysis efforts. The article explores some of the emerging themes in data discovery, data integration, linked data, and the combination of structured and unstructured data. PMID:25553272

Load Balancing Unstructured Adaptive Grids for CFD Problems

NASA Technical Reports Server (NTRS)

Biswas, Rupak; Oliker, Leonid

1996-01-01

Mesh adaption is a powerful tool for efficient unstructured-grid computations but causes load imbalance among processors on a parallel machine. A dynamic load balancing method is presented that balances the workload across all processors with a global view. After each parallel tetrahedral mesh adaption, the method first determines if the new mesh is sufficiently unbalanced to warrant a repartitioning. If so, the adapted mesh is repartitioned, with new partitions assigned to processors so that the redistribution cost is minimized. The new partitions are accepted only if the remapping cost is compensated by the improved load balance. Results indicate that this strategy is effective for large-scale scientific computations on distributed-memory multiprocessors.

Subspace projection method for unstructured searches with noisy quantum oracles using a signal-based quantum emulation device

NASA Astrophysics Data System (ADS)

La Cour, Brian R.; Ostrove, Corey I.

2017-01-01

This paper describes a novel approach to solving unstructured search problems using a classical, signal-based emulation of a quantum computer. The classical nature of the representation allows one to perform subspace projections in addition to the usual unitary gate operations. Although bandwidth requirements will limit the scale of problems that can be solved by this method, it can nevertheless provide a significant computational advantage for problems of limited size. In particular, we find that, for the same number of noisy oracle calls, the proposed subspace projection method provides a higher probability of success for finding a solution than does an single application of Grover's algorithm on the same device.

Coarsening strategies for unstructured multigrid techniques with application to anisotropic problems

NASA Technical Reports Server (NTRS)

Morano, E.; Mavriplis, D. J.; Venkatakrishnan, V.

1995-01-01

Over the years, multigrid has been demonstrated as an efficient technique for solving inviscid flow problems. However, for viscous flows, convergence rates often degrade. This is generally due to the required use of stretched meshes (i.e., the aspect-ratio AR = delta y/delta x is much less than 1) in order to capture the boundary layer near the body. Usual techniques for generating a sequence of grids that produce proper convergence rates on isotopic meshes are not adequate for stretched meshes. This work focuses on the solution of Laplace's equation, discretized through a Galerkin finite-element formulation on unstructured stretched triangular meshes. A coarsening strategy is proposed and results are discussed.

Coarsening Strategies for Unstructured Multigrid Techniques with Application to Anisotropic Problems

NASA Technical Reports Server (NTRS)

Morano, E.; Mavriplis, D. J.; Venkatakrishnan, V.

1996-01-01

Over the years, multigrid has been demonstrated as an efficient technique for solving inviscid flow problems. However, for viscous flows, convergence rates often degrade. This is generally due to the required use of stretched meshes (i.e. the aspect-ratio AR = (delta)y/(delta)x much less than 1) in order to capture the boundary layer near the body. Usual techniques for generating a sequence of grids that produce proper convergence rates on isotropic meshes are not adequate for stretched meshes. This work focuses on the solution of Laplace's equation, discretized through a Galerkin finite-element formulation on unstructured stretched triangular meshes. A coarsening strategy is proposed and results are discussed.

A User's Guide to AMR1D: An Instructional Adaptive Mesh Refinement Code for Unstructured Grids

NASA Technical Reports Server (NTRS)

deFainchtein, Rosalinda

1996-01-01

This report documents the code AMR1D, which is currently posted on the World Wide Web (http://sdcd.gsfc.nasa.gov/ESS/exchange/contrib/de-fainchtein/adaptive _mesh_refinement.html). AMR1D is a one-dimensional finite element fluid-dynamics solver, capable of adaptive mesh refinement (AMR). It was written as an instructional tool for AMR on unstructured mesh codes. It is meant to illustrate the minimum requirements for AMR on more than one dimension. For that purpose, it uses the same type of data structure that would be necessary on a two-dimensional AMR code (loosely following the algorithm described by Lohner).

Improving Unstructured Mesh Partitions for Multiple Criteria Using Mesh Adjacencies

DOE PAGES

Smith, Cameron W.; Rasquin, Michel; Ibanez, Dan; ...

2018-02-13

The scalability of unstructured mesh based applications depends on partitioning methods that quickly balance the computational work while reducing communication costs. Zhou et al. [SIAM J. Sci. Comput., 32 (2010), pp. 3201{3227; J. Supercomput., 59 (2012), pp. 1218{1228] demonstrated the combination of (hyper)graph methods with vertex and element partition improvement for PHASTA CFD scaling to hundreds of thousands of processes. Our work generalizes partition improvement to support balancing combinations of all the mesh entity dimensions (vertices, edges, faces, regions) in partitions with imbalances exceeding 70%. Improvement results are then presented for multiple entity dimensions on up to one million processesmore » on meshes with over 12 billion tetrahedral elements.« less

Solving Navier-Stokes Equations with Advanced Turbulence Models on Three-Dimensional Unstructured Grids

NASA Technical Reports Server (NTRS)

Wang, Qun-Zhen; Massey, Steven J.; Abdol-Hamid, Khaled S.; Frink, Neal T.

1999-01-01

USM3D is a widely-used unstructured flow solver for simulating inviscid and viscous flows over complex geometries. The current version (version 5.0) of USM3D, however, does not have advanced turbulence models to accurately simulate complicated flows. We have implemented two modified versions of the original Jones and Launder k-epsilon two-equation turbulence model and the Girimaji algebraic Reynolds stress model in USM3D. Tests have been conducted for two flat plate boundary layer cases, a RAE2822 airfoil and an ONERA M6 wing. The results are compared with those of empirical formulae, theoretical results and the existing Spalart-Allmaras one-equation model.

Improving Unstructured Mesh Partitions for Multiple Criteria Using Mesh Adjacencies

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

Smith, Cameron W.; Rasquin, Michel; Ibanez, Dan

The scalability of unstructured mesh based applications depends on partitioning methods that quickly balance the computational work while reducing communication costs. Zhou et al. [SIAM J. Sci. Comput., 32 (2010), pp. 3201{3227; J. Supercomput., 59 (2012), pp. 1218{1228] demonstrated the combination of (hyper)graph methods with vertex and element partition improvement for PHASTA CFD scaling to hundreds of thousands of processes. Our work generalizes partition improvement to support balancing combinations of all the mesh entity dimensions (vertices, edges, faces, regions) in partitions with imbalances exceeding 70%. Improvement results are then presented for multiple entity dimensions on up to one million processesmore » on meshes with over 12 billion tetrahedral elements.« less

Wind-US Flow Calculations for the M2129 S-Duct Using Structured and Unstructured Grids

NASA Technical Reports Server (NTRS)

Mohler, Stanley R., Jr.

2003-01-01

Computational Fluid Dynamics (CFD) flow solutions for the M2129 diffusing S-duct with and without vane effectors were computed by the Wind-US flow solver. Both structured and unstructured 3-D grids were used. Without vane effectors, the duct exhibited massive flow separation in both experiment and CFD. With vane effectors installed, the flow remained attached and aerodynamic losses were reduced. Total pressure recovery and distortion near the duct outlet were computed from the solutions and compared favorably to experimental values. These calculations are part of a validation effort for the Wind-US code. They also provide an example case to aid engineers in learning to use the Wind-US software.

NLP-PIER: A Scalable Natural Language Processing, Indexing, and Searching Architecture for Clinical Notes.

PubMed

McEwan, Reed; Melton, Genevieve B; Knoll, Benjamin C; Wang, Yan; Hultman, Gretchen; Dale, Justin L; Meyer, Tim; Pakhomov, Serguei V

2016-01-01

Many design considerations must be addressed in order to provide researchers with full text and semantic search of unstructured healthcare data such as clinical notes and reports. Institutions looking at providing this functionality must also address the big data aspects of their unstructured corpora. Because these systems are complex and demand a non-trivial investment, there is an incentive to make the system capable of servicing future needs as well, further complicating the design. We present architectural best practices as lessons learned in the design and implementation NLP-PIER (Patient Information Extraction for Research), a scalable, extensible, and secure system for processing, indexing, and searching clinical notes at the University of Minnesota.

A Structured and Unstructured grid Relocatable ocean platform for Forecasting (SURF)

NASA Astrophysics Data System (ADS)

Trotta, Francesco; Fenu, Elisa; Pinardi, Nadia; Bruciaferri, Diego; Giacomelli, Luca; Federico, Ivan; Coppini, Giovanni

2016-11-01

We present a numerical platform named Structured and Unstructured grid Relocatable ocean platform for Forecasting (SURF). The platform is developed for short-time forecasts and is designed to be embedded in any region of the large-scale Mediterranean Forecasting System (MFS) via downscaling. We employ CTD data collected during a campaign around the Elba island to calibrate and validate SURF. The model requires an initial spin up period of a few days in order to adapt the initial interpolated fields and the subsequent solutions to the higher-resolution nested grids adopted by SURF. Through a comparison with the CTD data, we quantify the improvement obtained by SURF model compared to the coarse-resolution MFS model.

Parallel Cartesian grid refinement for 3D complex flow simulations

NASA Astrophysics Data System (ADS)

Angelidis, Dionysios; Sotiropoulos, Fotis

2013-11-01

A second order accurate method for discretizing the Navier-Stokes equations on 3D unstructured Cartesian grids is presented. Although the grid generator is based on the oct-tree hierarchical method, fully unstructured data-structure is adopted enabling robust calculations for incompressible flows, avoiding both the need of synchronization of the solution between different levels of refinement and usage of prolongation/restriction operators. The current solver implements a hybrid staggered/non-staggered grid layout, employing the implicit fractional step method to satisfy the continuity equation. The pressure-Poisson equation is discretized by using a novel second order fully implicit scheme for unstructured Cartesian grids and solved using an efficient Krylov subspace solver. The momentum equation is also discretized with second order accuracy and the high performance Newton-Krylov method is used for integrating them in time. Neumann and Dirichlet conditions are used to validate the Poisson solver against analytical functions and grid refinement results to a significant reduction of the solution error. The effectiveness of the fractional step method results in the stability of the overall algorithm and enables the performance of accurate multi-resolution real life simulations. This material is based upon work supported by the Department of Energy under Award Number DE-EE0005482.

A hybrid Boundary Element Unstructured Transmission-line (BEUT) method for accurate 2D electromagnetic simulation

NASA Astrophysics Data System (ADS)

Simmons, Daniel; Cools, Kristof; Sewell, Phillip

2016-11-01

Time domain electromagnetic simulation tools have the ability to model transient, wide-band applications, and non-linear problems. The Boundary Element Method (BEM) and the Transmission Line Modeling (TLM) method are both well established numerical techniques for simulating time-varying electromagnetic fields. The former surface based method can accurately describe outwardly radiating fields from piecewise uniform objects and efficiently deals with large domains filled with homogeneous media. The latter volume based method can describe inhomogeneous and non-linear media and has been proven to be unconditionally stable. Furthermore, the Unstructured TLM (UTLM) enables modelling of geometrically complex objects by using triangular meshes which removes staircasing and unnecessary extensions of the simulation domain. The hybridization of BEM and UTLM which is described in this paper is named the Boundary Element Unstructured Transmission-line (BEUT) method. It incorporates the advantages of both methods. The theory and derivation of the 2D BEUT method is described in this paper, along with any relevant implementation details. The method is corroborated by studying its correctness and efficiency compared to the traditional UTLM method when applied to complex problems such as the transmission through a system of Luneburg lenses and the modelling of antenna radomes for use in wireless communications.