Revealing the global map of protein folding space by large-scale simulations

NASA Astrophysics Data System (ADS)

Sinner, Claude; Lutz, Benjamin; Verma, Abhinav; Schug, Alexander

2015-12-01

The full characterization of protein folding is a remarkable long-standing challenge both for experiment and simulation. Working towards a complete understanding of this process, one needs to cover the full diversity of existing folds and identify the general principles driving the process. Here, we want to understand and quantify the diversity in folding routes for a large and representative set of protein topologies covering the full range from all alpha helical topologies towards beta barrels guided by the key question: Does the majority of the observed routes contribute to the folding process or only a particular route? We identified a set of two-state folders among non-homologous proteins with a sequence length of 40-120 residues. For each of these proteins, we ran native-structure based simulations both with homogeneous and heterogeneous contact potentials. For each protein, we simulated dozens of folding transitions in continuous uninterrupted simulations and constructed a large database of kinetic parameters. We investigate folding routes by tracking the formation of tertiary structure interfaces and discuss whether a single specific route exists for a topology or if all routes are equiprobable. These results permit us to characterize the complete folding space for small proteins in terms of folding barrier ΔG‡, number of routes, and the route specificity RT.

The Jeanie Point complex revisited

USGS Publications Warehouse

Dumoulin, Julie A.; Miller, Martha L.

1984-01-01

The so-called Jeanie Point complex is a distinctive package of rocks within the Orca Group, a Tertiary turbidite sequence. The rocks crop out on the southeast coast of Montague Island, Prince William Sound, approximately 3 km northeast of Jeanie Point (loc. 7, fig. 44). These rocks consist dominantly of fine-grained limestone and lesser amounts of siliceous limestone, chert, tuff, mudstone, argillite, and sandstone (fig. 47). The Jeanie Point rocks also differ from those typical of the Orca Group in their fold style. Thus, the Orca Group of the area is isoclinally folded on a large scale (tens to hundreds of meters), whereas the Jeanie Point rocks are tightly folded on a 1- to 3- m-wavelength scale (differences in rock competency may be responsible for this variation in fold style).

Physical and chemical controls on ore shoots - insights from 3D modeling of an orogenic gold deposit

NASA Astrophysics Data System (ADS)

Vollgger, S. A.; Tomkins, A. G.; Micklethwaite, S.; Cruden, A. R.; Wilson, C. J. L.

2016-12-01

Many ore deposits have irregular grade distributions with localized elongate and well-mineralized rock volumes commonly referred to as ore shoots. The chemical and physical processes that control ore shoot formation are rarely understood, although transient episodes of elevated permeability are thought to be important within the brittle and brittle-ductile crust, due to faulting and fracturing associated with earthquake-aftershock sequences or earthquake swarms. We present data from an orogenic gold deposit in Australia where the bulk of the gold is contained in abundant fine arsenopyrite crystals associated with a fault-vein network within tight upright folds. The deposit-scale fault network is connected to a deeper network of thrust faults (tens of kilometers long). Using 3D implicit modeling of geochemical data, based on radial basis functions, gold grades and gold-arsenic element ratios were interpolated and related to major faults, vein networks and late intrusions. Additionally, downhole bedding measurements were used to model first order (mine-scale) fold structures. The results show that ore shoot plunges are not parallel with mine-scale or regional fold plunges, and that bedding parallel faults related to flexural slip folding play a pivotal role on ore shoot attitudes. 3D fault slip and dilation tendency analysis indicate that fault reactivation and formation of linking faults are associated with large volumes of high-grade ore. We suggest slip events on the large-scale thrust network allowed mineralizing fluids to rapidly migrate over large distances and become supersaturated in elements such as gold, promoting widespread precipitation and high nucleation densities of arsenopyrite upon fluid-rock interaction at trap sites within the deposit.

An algorithm for generating modular hierarchical neural network classifiers: a step toward larger scale applications

NASA Astrophysics Data System (ADS)

Roverso, Davide

2003-08-01

Many-class learning is the problem of training a classifier to discriminate among a large number of target classes. Together with the problem of dealing with high-dimensional patterns (i.e. a high-dimensional input space), the many class problem (i.e. a high-dimensional output space) is a major obstacle to be faced when scaling-up classifier systems and algorithms from small pilot applications to large full-scale applications. The Autonomous Recursive Task Decomposition (ARTD) algorithm is here proposed as a solution to the problem of many-class learning. Example applications of ARTD to neural classifier training are also presented. In these examples, improvements in training time are shown to range from 4-fold to more than 30-fold in pattern classification tasks of both static and dynamic character.

Accelerating large-scale protein structure alignments with graphics processing units

PubMed Central

2012-01-01

Background Large-scale protein structure alignment, an indispensable tool to structural bioinformatics, poses a tremendous challenge on computational resources. To ensure structure alignment accuracy and efficiency, efforts have been made to parallelize traditional alignment algorithms in grid environments. However, these solutions are costly and of limited accessibility. Others trade alignment quality for speedup by using high-level characteristics of structure fragments for structure comparisons. Findings We present ppsAlign, a parallel protein structure Alignment framework designed and optimized to exploit the parallelism of Graphics Processing Units (GPUs). As a general-purpose GPU platform, ppsAlign could take many concurrent methods, such as TM-align and Fr-TM-align, into the parallelized algorithm design. We evaluated ppsAlign on an NVIDIA Tesla C2050 GPU card, and compared it with existing software solutions running on an AMD dual-core CPU. We observed a 36-fold speedup over TM-align, a 65-fold speedup over Fr-TM-align, and a 40-fold speedup over MAMMOTH. Conclusions ppsAlign is a high-performance protein structure alignment tool designed to tackle the computational complexity issues from protein structural data. The solution presented in this paper allows large-scale structure comparisons to be performed using massive parallel computing power of GPU. PMID:22357132

Sub-seismic scale folding and thrusting within an exposed mass transport deposit: A case study from NW Argentina

NASA Astrophysics Data System (ADS)

Sobiesiak, Matheus S.; Alsop, G. Ian; Kneller, Ben; Milana, Juan Pablo

2017-03-01

While imaging of mass transport deposits (MTDs) by seismic reflection techniques commonly reveals thrusts and large blocks that affect entire deposits, associated systems of folds are generally less apparent as they are typically below the limits of seismic resolution. However, such sub-seismic scale structures are important as they permit the direction of emplacement, gross kinematics and internal strain within MTDs to be determined. Here we present a rigorous description of two outcrop-scale MTDs exposed in La Peña gorge, northwestern Argentina. These Carboniferous MTDs enable us to illustrate structural changes from a compressional domain, marked by sets of imbricated sandstone layers, into an extensional domain, characterized by sheared blocks of sandstone embedded in a finer matrix. Folds may be progressively modified during slump translation, resulting in asymmetric folds, which undergo subsequent deformation leading to sheared fold limbs together with detached and rotated fold hinges. In order to constrain transport directions within the MTDs, we measured fold hinges, mud clast alignment, and thrust planes as kinematic indicators. We propose emplacement models for both MTDs based on the overall deformational behaviour of sandstone beds during translation. The first model is based on the internal geometries and structures of a fault-dominated MTD, and the second model is based on layer-normal shearing in a fold-dominated MTD.

Comparison of concentric needle versus hooked-wire electrodes in the canine larynx.

PubMed

Jaffe, D M; Solomon, N P; Robinson, R A; Hoffman, H T; Luschei, E S

1998-05-01

The use of a specific electrode type in laryngeal electromyography has not been standardized. Laryngeal electromyography is usually performed with hooked-wire electrodes or concentric needle electrodes. Hooked-wire electrodes have the advantage of allowing laryngeal movement with ease and comfort, whereas the concentric needle electrodes have benefits from a technical aspect and may be advanced, withdrawn, or redirected during attempts to appropriately place the electrode. This study examines whether hooked-wire electrodes permit more stable recordings than standard concentric needle electrodes at rest and after large-scale movements of the larynx and surrounding structures. A histologic comparison of tissue injury resulting from placement and removal of the two electrode types is also made by evaluation of the vocal folds. Electrodes were percutaneously placed into the thyroarytenoid muscles of 10 adult canines. Amplitude of electromyographic activity was measured and compared during vagal stimulation before and after large-scale laryngeal movements. Signal consistency over time was examined. Animals were killed and vocal fold injury was graded and compared histologically. Waveform morphology did not consistently differ between electrode types. The variability of electromyographic amplitude was greater for the hooked-wire electrode (p < 0.05), whereas the mean amplitude measures before and after large-scale laryngeal movements did not differ (p > 0.05). Inflammatory responses and hematoma formation were also similar. Waveform morphology of electromyographic signals registered from both electrode types show similar complex action potentials. There is no difference between the hooked-wire electrode and the concentric needle electrode in terms of electrode stability or vocal fold injury in the thyroarytenoid muscle after large-scale laryngeal movements.

Converging flow and anisotropy cause large-scale folding in Greenland's ice sheet.

PubMed

Bons, Paul D; Jansen, Daniela; Mundel, Felicitas; Bauer, Catherine C; Binder, Tobias; Eisen, Olaf; Jessell, Mark W; Llorens, Maria-Gema; Steinbach, Florian; Steinhage, Daniel; Weikusat, Ilka

2016-04-29

The increasing catalogue of high-quality ice-penetrating radar data provides a unique insight in the internal layering architecture of the Greenland ice sheet. The stratigraphy, an indicator of past deformation, highlights irregularities in ice flow and reveals large perturbations without obvious links to bedrock shape. In this work, to establish a new conceptual model for the formation process, we analysed the radar data at the onset of the Petermann Glacier, North Greenland, and created a three-dimensional model of several distinct stratigraphic layers. We demonstrate that the dominant structures are cylindrical folds sub-parallel to the ice flow. By numerical modelling, we show that these folds can be formed by lateral compression of mechanically anisotropic ice, while a general viscosity contrast between layers would not lead to folding for the same boundary conditions. We conclude that the folds primarily form by converging flow as the mechanically anisotropic ice is channelled towards the glacier.

Converging flow and anisotropy cause large-scale folding in Greenland's ice sheet

NASA Astrophysics Data System (ADS)

Bons, Paul D.; Jansen, Daniela; Mundel, Felicitas; Bauer, Catherine C.; Binder, Tobias; Eisen, Olaf; Jessell, Mark W.; Llorens, Maria-Gema; Steinbach, Florian; Steinhage, Daniel; Weikusat, Ilka

2016-04-01

The increasing catalogue of high-quality ice-penetrating radar data provides a unique insight in the internal layering architecture of the Greenland ice sheet. The stratigraphy, an indicator of past deformation, highlights irregularities in ice flow and reveals large perturbations without obvious links to bedrock shape. In this work, to establish a new conceptual model for the formation process, we analysed the radar data at the onset of the Petermann Glacier, North Greenland, and created a three-dimensional model of several distinct stratigraphic layers. We demonstrate that the dominant structures are cylindrical folds sub-parallel to the ice flow. By numerical modelling, we show that these folds can be formed by lateral compression of mechanically anisotropic ice, while a general viscosity contrast between layers would not lead to folding for the same boundary conditions. We conclude that the folds primarily form by converging flow as the mechanically anisotropic ice is channelled towards the glacier.

Large scale ab initio modeling of structurally uncharacterized antimicrobial peptides reveals known and novel folds.

PubMed

Kozic, Mara; Fox, Stephen J; Thomas, Jens M; Verma, Chandra S; Rigden, Daniel J

2018-05-01

Antimicrobial resistance within a wide range of infectious agents is a severe and growing public health threat. Antimicrobial peptides (AMPs) are among the leading alternatives to current antibiotics, exhibiting broad spectrum activity. Their activity is determined by numerous properties such as cationic charge, amphipathicity, size, and amino acid composition. Currently, only around 10% of known AMP sequences have experimentally solved structures. To improve our understanding of the AMP structural universe we have carried out large scale ab initio 3D modeling of structurally uncharacterized AMPs that revealed similarities between predicted folds of the modeled sequences and structures of characterized AMPs. Two of the peptides whose models matched known folds are Lebocin Peptide 1A (LP1A) and Odorranain M, predicted to form β-hairpins but, interestingly, to lack the intramolecular disulfide bonds, cation-π or aromatic interactions that generally stabilize such AMP structures. Other examples include Ponericin Q42, Latarcin 4a, Kassinatuerin 1, Ceratotoxin D, and CPF-B1 peptide, which have α-helical folds, as well as mixed αβ folds of human Histatin 2 peptide and Garvicin A which are, to the best of our knowledge, the first linear αββ fold AMPs lacking intramolecular disulfide bonds. In addition to fold matches to experimentally derived structures, unique folds were also obtained, namely for Microcin M and Ipomicin. These results help in understanding the range of protein scaffolds that naturally bear antimicrobial activity and may facilitate protein design efforts towards better AMPs. © 2018 The Authors Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc.

Structural analysis of sheath folds in the Sylacauga Marble Group, Talladega slate belt, southern Appalachians

USGS Publications Warehouse

Mies, J.W.

1993-01-01

Remnant blocks of marble from the Moretti-Harrah dimension-stone quarry provide excellent exposure of meter-scale sheath folds. Tubular structures with elliptical cross-sections (4 ???Ryz ??? 5) are the most common expression of the folds. The tubes are elongate subparallel to stretching lineation and are defined by centimeter-scale layers of schist. Eccentrically nested elliptical patterns and opposing asymmetry of folds ('S' and 'Z') are consistent with the sheath-fold interpretation. Sheath folds are locally numerous in the Moretti-Harrah quarry but are not widely distributed in the Sylacauga Marble Group; reconnaissance in neighboring quarries provided no additional observations. The presence of sheath folds in part of the Talladega slate belt indicates a local history of plastic, non-coaxial deformation. Such a history of deformation is substantiated by petrographic study of an extracted hinge from the Moretti-Harrah quarry. The sheath folds are modeled as due to passive amplification of initial structures during simple shear, using both analytic geometry and graphic simulation. As indicated by these models, relatively large shear strains (y ??? 9) and longitudinal initial structures are required. The shear strain presumably relates to NW-directed displacement of overlying crystalline rocks during late Paleozoic orogeny. ?? 1993.

Unraveling metamaterial properties in zigzag-base folded sheets.

PubMed

Eidini, Maryam; Paulino, Glaucio H

2015-09-01

Creating complex spatial objects from a flat sheet of material using origami folding techniques has attracted attention in science and engineering. In the present work, we use the geometric properties of partially folded zigzag strips to better describe the kinematics of known zigzag/herringbone-base folded sheet metamaterials such as Miura-ori. Inspired by the kinematics of a one-degree of freedom zigzag strip, we introduce a class of cellular folded mechanical metamaterials comprising different scales of zigzag strips. This class of patterns combines origami folding techniques with kirigami. Using analytical and numerical models, we study the key mechanical properties of the folded materials. We show that our class of patterns, by expanding on the design space of Miura-ori, is appropriate for a wide range of applications from mechanical metamaterials to deployable structures at small and large scales. We further show that, depending on the geometry, these materials exhibit either negative or positive in-plane Poisson's ratios. By introducing a class of zigzag-base materials in the current study, we unify the concept of in-plane Poisson's ratio for similar materials in the literature and extend it to the class of zigzag-base folded sheet materials.

Evidence from Fold Vergence for Coaxial Ductile Flow within the Otago Subduction Wedge, South Island, New Zealand

NASA Astrophysics Data System (ADS)

Rahl, J. M.; Brandon, M. T.

2001-12-01

There has been a long-standing debate about the tectonic significance of the highly folded Otago schist, which is exposed in the Otago uplift on the South Island of New Zealand. This uplift marks the forearc high of a long-lived subduction wedge that flanked the Mesozoic Gondwana margin. The exhumed metamorphic rocks record temperatures up to ~450 C and depths up to ~25 km. The dominant foliation is generally gently dipping, with attitudes that follow the form of the uplift. Mesoscale folds are common, and some regional-scale fold are recognized as well. Previous workers have argued that deformation within the Otago Schist resulted from trenchward shearing above a subducting oceanic plate, but there has been little evidence for systematic fold vergence across the uplift to support this idea. We describe here a new method for analysing the average vergence of a pervasively folded unit, with the goal to test the degree of non-coaxiality associated with ductile deformation within the Otago wedge. Our analysis exploits a new database, compiled by the New Zealand IGNS, which summarizes thousands of structural measurements for the Otago Schist. Vergence is defined in the usual manner as the asymmetry of the fold relative to its axial plane. This asymmetry is attributed to shear-induced rotation at the scale of the fold. Non-coaxial shear can be locally induced, especially in strongly layered schist sequences. We want to know if the fold vergence is systematically developed at the regional scale. Each fold is represented by a vector parallel to the fold axis, with a direction defined by the right-handed rotation implied by the vergence. We argue that the net vergence is well approximated by the Fisher vector mean of the vergence vectors. In addition, we consider the spatial distribution of the vergence vectors across the uplift, with a specific focus on the structural boundary between the Caples and Torlesse, two accretionary units that make up the wedge. We find that there is no systematic vergence at the regional scale or localized along the Torlesse/Caples boundary. We do find local domains at the 10 km scale with a consistent vergence direction, but at large scales, the vergence pattern becomes averaged out. These result support the idea that the Otago schist formed by vertical shortening within a regional-scale coaxial flow field, perhaps driven by underplating beneath the uplift. Furthermore, the lack of a regional-scale vergence implies very weak coupling across the subduction zone.

Numerical modelling of the role of salt in continental collision: An application to the southeast Zagros fold-and-thrust belt

NASA Astrophysics Data System (ADS)

Ghazian, Reza Khabbaz; Buiter, Susanne J. H.

2014-09-01

The Zagros fold-and-thrust belt formed in the collision of Arabia with Central Iran. Its sedimentary sequence is characterised by the presence of several weak layers that may control the style of folding and thrusting. We use 2-D thermo-mechanical models to investigate the role of salt in the southeast Zagros fold-and-thrust belt. We constrain the crustal and lithospheric thickness, sedimentary stratification, convergence velocity, and thermal structure of the models from available geological and geophysical data. We find that the thick basal layer of Hormuz salt in models on the scale of the upper-mantle decouples the overlying sediments from the basement and localises deformation in the sediments by trench-verging shear bands. In the collision stage of the models, basement dips with + 1° towards the trench. Including the basal Hormuz salt improves the fit of predicted topography to observed topography. We use the kinematic results and thermal structure of this large-scale model as the initial conditions of a series of upper-crustal-scale models. These models aim to investigate the effects of basal and intervening weak layers, salt strength, basal dip, and lateral salt distribution on deformation style of the simply folded Zagros. Our results show that in addition to the Hormuz salt at the base of the sedimentary cover, at least one intervening weak layer is required to initiate fold-dominated deformation in the southeast Zagros. We find that an upper-crustal-scale model, with a basal and three internal weak layers with viscosities between 5 × 1018 and 1019 Pa s, and a basement that dips + 1° towards the trench, best reproduces present-day topography and the regular folding of the sedimentary layers of the simply folded Zagros.

Influence of tectonic folding on rockfall susceptibility, American Fork Canyon, Utah, USA

USGS Publications Warehouse

Coe, J.A.; Harp, E.L.

2007-01-01

We examine rockfall susceptibility of folded strata in the Sevier fold-thrust belt exposed in American Fork Canyon in north-central Utah. Large-scale geologic mapping, talus production data, rock-mass-quality measurements, and historical rockfall data indicate that rockfall susceptibility is correlated with limb dip and curvature of the folded, cliff-forming Mississippian limestones. On fold limbs, rockfall susceptibility increases as dip increases. This relation is controlled by several factors, including an increase in adverse dip conditions and apertures of discontinuities, and shearing by flexural slip during folding that has reduced the friction angles of discontinuities by smoothing surface asperities. Susceptibility is greater in fold hinge zones than on adjacent limbs primarily because there are greater numbers of discontinuities in hinge zones. We speculate that susceptibility increases in hinge zones as fold curvature becomes tighter.

Timing of isoclinal folds in multiply deformed high metamorphic grade region using FIA succession

NASA Astrophysics Data System (ADS)

Cao, Hui; Cai, Zhihui

2013-04-01

Multiply deformed and isoclinally folded interlayered high metamorphic grade gneisses and schists can be very difficult rocks for resolving early formed stratigraphic and structural relationships. When such rocks contain porphyroblasts a new approach is possible because of the way in which porphyroblast growth is affected by crenulation versus reactivation of compositional layering. The asymmetries of the overprinting foliations preserved as inclusion trails that define the FIAs can be used to investigate whether an enigmatic isoclinal fold is an antiform or synform. This approach also reveals when the fold first formed during the tectonic history of the region. Isoclinally folded rocks in the Arkansas River region of Central Colorado contain relics of fold hinges that have been very difficult to ascertain whether they are antiforms or synforms because of younger refolding effects and the locally truncated nature of coarse compositional layering. With the realization that rocks with a schistosity parallel to bedding (S0 parallel S1) have undergone lengthy histories of deformation that predate the obvious first deformation came recognition that large scale regional folds can form early during this process and be preserved throughout orogenesis. This extensive history is lost within the matrix because of reactivational shear on the compositional layering. However, it can be extracted by measuring FIAs. Recent work using this approach has revealed that the trends of axial planes of all map scale folds, when plotted on a rose diagram, strikingly reflect the FIA trends. That is, although it was demonstrated that the largest scale regional folds commonly form early in the total history, other folds can form and be preserved from subsequent destruction in the strain shadows of plutons or through the partitioning of deformation due to heterogeneities at depth.

Converging flow and anisotropy cause large-scale folding in Greenland's ice sheet

PubMed Central

Bons, Paul D.; Jansen, Daniela; Mundel, Felicitas; Bauer, Catherine C.; Binder, Tobias; Eisen, Olaf; Jessell, Mark W.; Llorens, Maria-Gema; Steinbach, Florian; Steinhage, Daniel; Weikusat, Ilka

2016-01-01

The increasing catalogue of high-quality ice-penetrating radar data provides a unique insight in the internal layering architecture of the Greenland ice sheet. The stratigraphy, an indicator of past deformation, highlights irregularities in ice flow and reveals large perturbations without obvious links to bedrock shape. In this work, to establish a new conceptual model for the formation process, we analysed the radar data at the onset of the Petermann Glacier, North Greenland, and created a three-dimensional model of several distinct stratigraphic layers. We demonstrate that the dominant structures are cylindrical folds sub-parallel to the ice flow. By numerical modelling, we show that these folds can be formed by lateral compression of mechanically anisotropic ice, while a general viscosity contrast between layers would not lead to folding for the same boundary conditions. We conclude that the folds primarily form by converging flow as the mechanically anisotropic ice is channelled towards the glacier. PMID:27126274

Efficiency of Adaptive Temperature-Based Replica Exchange for Sampling Large-Scale Protein Conformational Transitions.

PubMed

Zhang, Weihong; Chen, Jianhan

2013-06-11

Temperature-based replica exchange (RE) is now considered a principal technique for enhanced sampling of protein conformations. It is also recognized that existence of sharp cooperative transitions (such as protein folding/unfolding) can lead to temperature exchange bottlenecks and significantly reduce the sampling efficiency. Here, we revisit two adaptive temperature-based RE protocols, namely, exchange equalization (EE) and current maximization (CM), that were previously examined using atomistic simulations (Lee and Olson, J. Chem. Physics2011, 134, 24111). Both protocols aim to overcome exchange bottlenecks by adaptively adjusting the simulation temperatures, either to achieve uniform exchange rates (in EE) or to maximize temperature diffusion (CM). By designing a realistic yet computationally tractable coarse-grained protein model, one can sample many reversible folding/unfolding transitions using conventional constant temperature molecular dynamics (MD), standard REMD, EE-REMD, and CM-REMD. This allows rigorous evaluation of the sampling efficiency, by directly comparing the rates of folding/unfolding transitions and convergence of various thermodynamic properties of interest. The results demonstrate that both EE and CM can indeed enhance temperature diffusion compared to standard RE, by ∼3- and over 10-fold, respectively. Surprisingly, the rates of reversible folding/unfolding transitions are similar in all three RE protocols. The convergence rates of several key thermodynamic properties, including the folding stability and various 1D and 2D free energy surfaces, are also similar. Therefore, the efficiency of RE protocols does not appear to be limited by temperature diffusion, but by the inherent rates of spontaneous large-scale conformational rearrangements. This is particularly true considering that virtually all RE simulations of proteins in practice involve exchange attempt frequencies (∼ps(-1)) that are several orders of magnitude faster than the slowest protein motions (∼μs(-1)). Our results also suggest that the efficiency of RE will not likely be improved by other protocols that aim to accelerate exchange or temperature diffusion. Instead, protocols with some types of guided tempering will likely be necessary to drive faster large-scale conformational transitions.

Internal friction controls the speed of protein folding from a compact configuration.

PubMed

Pabit, Suzette A; Roder, Heinrich; Hagen, Stephen J

2004-10-05

Several studies have found millisecond protein folding reactions to be controlled by the viscosity of the solvent: Reducing the viscosity allows folding to accelerate. In the limit of very low solvent viscosity, however, one expects a different behavior. Internal interactions, occurring within the solvent-excluded interior of a compact molecule, should impose a solvent-independent upper limit to folding speed once the bulk diffusional motions become sufficiently rapid. Why has this not been observed? We have studied the effect of solvent viscosity on the folding of cytochrome c from a highly compact, late-stage intermediate configuration. Although the folding rate accelerates as the viscosity declines, it tends toward a finite limiting value approximately 10(5) s(-1) as the viscosity tends toward zero. This limiting rate is independent of the cosolutes used to adjust solvent friction. Therefore, interactions within the interior of a compact denatured polypeptide can limit the folding rate, but the limiting time scale is very fast. It is only observable when the solvent-controlled stages of folding are exceedingly rapid or else absent. Interestingly, we find a very strong temperature dependence in these "internal friction"-controlled dynamics, indicating a large energy scale for the interactions that govern reconfiguration within compact, near-native states of a protein.

Spatial Covariability of Temperature and Hydroclimate as a Function of Timescale During the Common Era

NASA Astrophysics Data System (ADS)

McKay, N.

2017-12-01

As timescale increases from years to centuries, the spatial scale of covariability in the climate system is hypothesized to increase as well. Covarying spatial scales are larger for temperature than for hydroclimate, however, both aspects of the climate system show systematic changes on large-spatial scales on orbital to tectonic timescales. The extent to which this phenomenon is evident in temperature and hydroclimate at centennial timescales is largely unknown. Recent syntheses of multidecadal to century-scale variability in hydroclimate during the past 2k in the Arctic, North America, and Australasia show little spatial covariability in hydroclimate during the Common Era. To determine 1) the evidence for systematic relationships between the spatial scale of climate covariability as a function of timescale, and 2) whether century-scale hydroclimate variability deviates from the relationship between spatial covariability and timescale, we quantify this phenomenon during the Common Era by calculating the e-folding distance in large instrumental and paleoclimate datasets. We calculate this metric of spatial covariability, at different timescales (1, 10 and 100-yr), for a large network of temperature and precipitation observations from the Global Historical Climatology Network (n=2447), from v2.0.0 of the PAGES2k temperature database (n=692), and from moisture-sensitive paleoclimate records North America, the Arctic, and the Iso2k project (n = 328). Initial results support the hypothesis that the spatial scale of covariability is larger for temperature, than for precipitation or paleoclimate hydroclimate indicators. Spatially, e-folding distances for temperature are largest at low latitudes and over the ocean. Both instrumental and proxy temperature data show clear evidence for increasing spatial extent as a function of timescale, but this phenomenon is very weak in the hydroclimate data analyzed here. In the proxy hydroclimate data, which are predominantly indicators of effective moisture, e-folding distance increases from annual to decadal timescales, but does not continue to increase to centennial timescales. Future work includes examining additional instrumental and proxy datasets of moisture variability, and extending the analysis to millennial timescales of variability.

Do faults trigger folding in the lithosphere?

NASA Astrophysics Data System (ADS)

Gerbault, Muriel; Burov, Eugenii B.; Poliakov, Alexei N. B.; Daignières, Marc

A number of observations reveal large periodic undulations within the oceanic and continental lithospheres. The question if these observations are the result of large-scale compressive instabilities, i.e. buckling, remains open. In this study, we support the buckling hypothesis by direct numerical modeling. We compare our results with the data on three most proeminent cases of the oceanic and continental folding-like deformation (Indian Ocean, Western Gobi (Central Asia) and Central Australia). We demonstrate that under reasonable tectonic stresses, folds can develop from brittle faults cutting through the brittle parts of a lithosphere. The predicted wavelengths and finite growth rates are in agreement with observations. We also show that within a continental lithosphere with thermal age greater than 400 My, either a bi-harmonic mode (two superimposed wavelengths, crustal and mantle one) or a coupled mode (mono-layer deformation) of inelastic folding can develop, depending on the strength and thickness of the lower crust.

Influence of the ventricular folds on a voice source with specified vocal fold motion1

PubMed Central

McGowan, Richard S.; Howe, Michael S.

2010-01-01

The unsteady drag on the vocal folds is the major source of sound during voiced speech. The drag force is caused by vortex shedding from the vocal folds. The influence of the ventricular folds (i.e., the “false” vocal folds that protrude into the vocal tract a short distance downstream of the glottis) on the drag and the voice source are examined in this paper by means of a theoretical model involving vortex sheets in a two-dimensional geometry. The effect of the ventricular folds on the output acoustic pressure is found to be small when the movement of the vocal folds is prescribed. It is argued that the effect remains small when fluid-structure interactions account for vocal fold movement. These conclusions can be justified mathematically when the characteristic time scale for change in the velocity of the glottal jet is large compared to the time it takes for a vortex disturbance to be convected through the vocal fold and ventricular fold region. PMID:20329852

Fabric Development in a Late-Hercynian Magmatic Strike-Slip Shear Zone in Southern Corsica: Indications of Melt-Supported Large-Scale Deformation Localization

NASA Astrophysics Data System (ADS)

Kruhl, J. H.; Vernon, R. H.

2009-05-01

The calc-alcaline granitoids of the Hercynian Corsica Batholith show a large-scale magmatic flow pattern, outlined by the alignment of large (mm-cm) euhedral feldspar crystals. The trend of the steep magmatic foliation is generally N-S in the northern part of the island, swings to approximately E-W orientation in the central part of the Batholith and back again to approximately N-S orientation in the southern part. This pattern is intensified by large-scale magmatic layering, mainly kilometer long lenses and layers of mafic and intermediate intrusions into the granitoids. On the macro- to micro-scale, magma mingling and mixing are present, reflecting the complex intrusion history and the compositional variability of the Corsica Batholith on different scales. Around the Golf of Valinco, a steep, sinistral magmatic shear zone is represented by E-W trending magmatic layering in mingled dioritic, tonalitic, and granitic magmas - previously misleadingly interpreted as migmatites - and by a magmatic flow foliation formed by the alignment of platy feldspar crystals, as well as amphibole and biotite. Characteristic magmatic structures include multiple thin layering, boudinage, monoclinic folding, melt-injected micro shear zones, and fragmenting and back- veining of dioritic enclaves. The intensity of grain alignment roughly correlates with the thickness of layers. It is low in thick and short boudins and high in cm-thin and cm-m long layers. The monoclinic folds refold the magmatic layering. Flat faces of amphibole and biotite grains are aligned in the axial planes of the folds. The feldspar crystals are locally recrystallized to a few large polygonal grains (up to 1 mm across), and quartz commonly shows chessboard subgrain patterns. No further indications of solid-state deformation are present. Field observations, as well as pattern quantification on variably oriented rock surfaces, indicate variations of crystal alignment and fabric anisotropy in cm- to more than 100m-wide bands parallel to the E-W oriented layering, and various stages of melt-present fragmentation. These variations are interpreted as variations of flow intensity and possibly strain-rate variation. The observations on the macro- as well as the micro-scale point to repeated injection of mafic to felsic magma and crystallization in the presence of a regional stress field. The resulting km-scale sinistral, sub-horizontal synmagmatic shear zone reflects large-scale movements during late-Hercynian crustal reorganization and represents an excellent example of localization of deformation into magma-enriched parts of the continental crust.

Deep crustal deformation by sheath folding in the Adirondack Mountains, USA

NASA Technical Reports Server (NTRS)

Mclelland, J. M.

1988-01-01

As described by McLelland and Isachsen, the southern half of the Adirondacks are underlain by major isoclinal (F sub 1) and open-upright (F sub 2) folds whose axes are parallel, trend approximately E-W, and plunge gently about the horizontal. These large structures are themselves folded by open upright folds trending NNE (F sub 3). It is pointed out that elongation lineations in these rocks are parallel to X of the finite strain ellipsoid developed during progressive rotational strain. The parallelism between F sub 1 and F sub 2 fold axes and elongation lineations led to the hypothesis that progressive rotational strain, with a west-directed tectonic transport, rotated earlier F sub 1-folds into parallelism with the evolving elongation lineation. Rotation is accomplished by ductile, passive flow of F sub 1-axes into extremely arcuate, E-W hinges. In order to test these hypotheses a number of large folds were mapped in the eastern Adirondacks. Other evidence supporting the existence of sheath folds in the Adirondacks is the presence, on a map scale, of synforms whose limbs pass through the vertical and into antiforms. This type of outcrop pattern is best explained by intersecting a horizontal plane with the double curvature of sheath folds. It is proposed that sheath folding is a common response of hot, ductile rocks to rotational strain at deep crustal levels. The recognition of sheath folds in the Adirondacks reconciles the E-W orientation of fold axes with an E-W elongation lineation.

Proteins with similar architecture exhibit similar large-scale dynamic behavior.

PubMed Central

Keskin, O; Jernigan, R L; Bahar, I

2000-01-01

We have investigated the similarities and differences in the computed dynamic fluctuations exhibited by six members of a protein fold family with a coarse-grained Gaussian network model. Specifically, we consider the cofactor binding fragment of CysB; the lysine/arginine/ornithine-binding protein (LAO); the enzyme porphobilinogen deaminase (PBGD); the ribose-binding protein (RBP); the N-terminal lobe of ovotransferrin in apo-form (apo-OVOT); and the leucine/isoleucine/valine-binding protein (LIVBP). All have domains that resemble a Rossmann fold, but there are also some significant differences. Results indicate that similar global dynamic behavior is preserved for the members of a fold family, and that differences usually occur in regions only where specific function is localized. The present work is a computational demonstration that the scaffold of a protein fold may be utilized for diverse purposes. LAO requires a bound ligand before it conforms to the large-scale fluctuation behavior of the three other members of the family, CysB, PBGD, and RBP, all of which contain a substrate (cofactor) at the active site cleft. The dynamics of the ligand-free enzymes LIVBP and apo-OVOT, on the other hand, concur with that of unliganded LAO. The present results suggest that it is possible to construct structure alignments based on dynamic fluctuation behavior. PMID:10733987

Polymer physics of chromosome large-scale 3D organisation

NASA Astrophysics Data System (ADS)

Chiariello, Andrea M.; Annunziatella, Carlo; Bianco, Simona; Esposito, Andrea; Nicodemi, Mario

2016-07-01

Chromosomes have a complex architecture in the cell nucleus, which serves vital functional purposes, yet its structure and folding mechanisms remain still incompletely understood. Here we show that genome-wide chromatin architecture data, as mapped by Hi-C methods across mammalian cell types and chromosomes, are well described by classical scaling concepts of polymer physics, from the sub-Mb to chromosomal scales. Chromatin is a complex mixture of different regions, folded in the conformational classes predicted by polymer thermodynamics. The contact matrix of the Sox9 locus, a region linked to severe human congenital diseases, is derived with high accuracy in mESCs and its molecular determinants identified by the theory; Sox9 self-assembles hierarchically in higher-order domains, involving abundant many-body contacts. Our approach is also applied to the Bmp7 locus. Finally, the model predictions on the effects of mutations on folding are tested against available data on a deletion in the Xist locus. Our results can help progressing new diagnostic tools for diseases linked to chromatin misfolding.

Large-Eddy Simulation of Internal Flow through Human Vocal Folds

NASA Astrophysics Data System (ADS)

Lasota, Martin; Šidlof, Petr

2018-06-01

The phonatory process occurs when air is expelled from the lungs through the glottis and the pressure drop causes flow-induced oscillations of the vocal folds. The flow fields created in phonation are highly unsteady and the coherent vortex structures are also generated. For accuracy it is essential to compute on humanlike computational domain and appropriate mathematical model. The work deals with numerical simulation of air flow within the space between plicae vocales and plicae vestibulares. In addition to the dynamic width of the rima glottidis, where the sound is generated, there are lateral ventriculus laryngis and sacculus laryngis included in the computational domain as well. The paper presents the results from OpenFOAM which are obtained with a large-eddy simulation using second-order finite volume discretization of incompressible Navier-Stokes equations. Large-eddy simulations with different subgrid scale models are executed on structured mesh. In these cases are used only the subgrid scale models which model turbulence via turbulent viscosity and Boussinesq approximation in subglottal and supraglottal area in larynx.

Camphor-Enabled Transfer and Mechanical Testing of Centimeter-Scale Ultrathin Films.

PubMed

Wang, Bin; Luo, Da; Li, Zhancheng; Kwon, Youngwoo; Wang, Meihui; Goo, Min; Jin, Sunghwan; Huang, Ming; Shen, Yongtao; Shi, Haofei; Ding, Feng; Ruoff, Rodney S

2018-05-21

Camphor is used to transfer centimeter-scale ultrathin films onto custom-designed substrates for mechanical (tensile) testing. Compared to traditional transfer methods using dissolving/peeling to remove the support-layers, camphor is sublimed away in air at low temperature, thereby avoiding additional stress on the as-transferred films. Large-area ultrathin films can be transferred onto hollow substrates without damage by this method. Tensile measurements are made on centimeter-scale 300 nm-thick graphene oxide film specimens, much thinner than the ≈2 μm minimum thickness of macroscale graphene-oxide films previously reported. Tensile tests were also done on two different types of large-area samples of adlayer free CVD-grown single-layer graphene supported by a ≈100 nm thick polycarbonate film; graphene stiffens this sample significantly, thus the intrinsic mechanical response of the graphene can be extracted. This is the first tensile measurement of centimeter-scale monolayer graphene films. The Young's modulus of polycrystalline graphene ranges from 637 to 793 GPa, while for near single-crystal graphene, it ranges from 728 to 908 GPa (folds parallel to the tensile loading direction) and from 683 to 775 GPa (folds orthogonal to the tensile loading direction), demonstrating the mechanical performance of large-area graphene in a size scale relevant to many applications. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Free Energy Landscape and Multiple Folding Pathways of an H-Type RNA Pseudoknot

PubMed Central

Bian, Yunqiang; Zhang, Jian; Wang, Jun; Wang, Jihua; Wang, Wei

2015-01-01

How RNA sequences fold to specific tertiary structures is one of the key problems for understanding their dynamics and functions. Here, we study the folding process of an H-type RNA pseudoknot by performing a large-scale all-atom MD simulation and bias-exchange metadynamics. The folding free energy landscapes are obtained and several folding intermediates are identified. It is suggested that the folding occurs via multiple mechanisms, including a step-wise mechanism starting either from the first helix or the second, and a cooperative mechanism with both helices forming simultaneously. Despite of the multiple mechanism nature, the ensemble folding kinetics estimated from a Markov state model is single-exponential. It is also found that the correlation between folding and binding of metal ions is significant, and the bound ions mediate long-range interactions in the intermediate structures. Non-native interactions are found to be dominant in the unfolded state and also present in some intermediates, possibly hinder the folding process of the RNA. PMID:26030098

High Pressure ZZ-Exchange NMR Reveals Key Features of Protein Folding Transition States.

PubMed

Zhang, Yi; Kitazawa, Soichiro; Peran, Ivan; Stenzoski, Natalie; McCallum, Scott A; Raleigh, Daniel P; Royer, Catherine A

2016-11-23

Understanding protein folding mechanisms and their sequence dependence requires the determination of residue-specific apparent kinetic rate constants for the folding and unfolding reactions. Conventional two-dimensional NMR, such as HSQC experiments, can provide residue-specific information for proteins. However, folding is generally too fast for such experiments. ZZ-exchange NMR spectroscopy allows determination of folding and unfolding rates on much faster time scales, yet even this regime is not fast enough for many protein folding reactions. The application of high hydrostatic pressure slows folding by orders of magnitude due to positive activation volumes for the folding reaction. We combined high pressure perturbation with ZZ-exchange spectroscopy on two autonomously folding protein domains derived from the ribosomal protein, L9. We obtained residue-specific apparent rates at 2500 bar for the N-terminal domain of L9 (NTL9), and rates at atmospheric pressure for a mutant of the C-terminal domain (CTL9) from pressure dependent ZZ-exchange measurements. Our results revealed that NTL9 folding is almost perfectly two-state, while small deviations from two-state behavior were observed for CTL9. Both domains exhibited large positive activation volumes for folding. The volumetric properties of these domains reveal that their transition states contain most of the internal solvent excluded voids that are found in the hydrophobic cores of the respective native states. These results demonstrate that by coupling it with high pressure, ZZ-exchange can be extended to investigate a large number of protein conformational transitions.

NASA Office of Aeronautics and Space Technology Summer Workshop. Volume 3: Navigation, guidance and control panel

NASA Technical Reports Server (NTRS)

1975-01-01

User technology requirements are identified in relation to needed technology advancement for future space missions in the areas of navigation, guidance, and control. Emphasis is placed on: reduction of mission support cost by 50% through autonomous operation, a ten-fold increase in mission output through improved pointing and control, and a hundred-fold increase in human productivity in space through large-scale teleoperator applications.

Spanning the scales of mechanical metamaterials using time domain simulations in transformed crystals, graphene flakes and structured soils

NASA Astrophysics Data System (ADS)

Aznavourian, Ronald; Puvirajesinghe, Tania M.; Brûlé, Stéphane; Enoch, Stefan; Guenneau, Sébastien

2017-11-01

We begin with a brief historical survey of discoveries of quasi-crystals and graphene, and then introduce the concept of transformation crystallography, which consists of the application of geometric transforms to periodic structures. We consider motifs with three-fold, four-fold and six-fold symmetries according to the crystallographic restriction theorem. Furthermore, we define motifs with five-fold symmetry such as quasi-crystals generated by a cut-and-projection method from periodic structures in higher-dimensional space. We analyze elastic wave propagation in the transformed crystals and (Penrose-type) quasi-crystals with the finite difference time domain freeware SimSonic. We consider geometric transforms underpinning the design of seismic cloaks with square, circular, elliptical and peanut shapes in the context of honeycomb crystals that can be viewed as scaled-up versions of graphene. Interestingly, the use of morphing techniques leads to the design of cloaks with interpolated geometries reminiscent of Victor Vasarely’s artwork. Employing the case of transformed graphene-like (honeycomb) structures allows one to draw useful analogies between large-scale seismic metamaterials such as soils structured with columns of concrete or grout with soil and nanoscale biochemical metamaterials. We further identify similarities in designs of cloaks for elastodynamic and hydrodynamic waves and cloaks for diffusion (heat or mass) processes, as these are underpinned by geometric transforms. Experimental data extracted from field test analysis of soil structured with boreholes demonstrates the application of crystallography to large scale phononic crystals, coined as seismic metamaterials, as they might exhibit low frequency stop bands. This brings us to the outlook of mechanical metamaterials, with control of phonon emission in graphene through extreme anisotropy, attenuation of vibrations of suspension bridges via low frequency stop bands and the concept of transformed meta-cities. We conclude that these novel materials hold strong applications spanning different disciplines or across different scales from biophysics to geophysics.

Accommodating Thickness in Origami-Based Deployable Arrays

NASA Technical Reports Server (NTRS)

Zirbel, Shannon A.; Magleby, Spencer P.; Howell, Larry L.; Lang, Robert J.; Thomson, Mark W.; Sigel, Deborah A.; Walkemeyer, Phillip E.; Trease, Brian P.

2013-01-01

The purpose of this work is to create deployment systems with a large ratio of stowed-to-deployed diameter. Deployment from a compact form to a final flat state can be achieved through origami-inspired folding of panels. There are many models capable of this motion when folded in a material with negligible thickness; however, when the application requires the folding of thick, rigid panels, attention must be paid to the effect of material thickness not only on the final folded state, but also during the folding motion (i.e., the panels must not be required to flex to attain the final folded form). The objective is to develop new methods for deployment from a compact folded form to a large circular array (or other final form). This paper describes a mathematical model for modifying the pattern to accommodate material thickness in the context of the design, modeling, and testing of a deployable system inspired by an origami six-sided flasher model. The model is demonstrated in hardware as a 1/20th scale prototype of a deployable solar array for space applications. The resulting prototype has a ratio of stowed-to-deployed diameter of 9.2 (or 1.25 m deployed outer diameter to 0.136 m stowed outer diameter).

Mesozoic contractile and extensional structures in the Boyer Gap area, northern Dome Rock Mountains, Arizona

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

Boettcher, S.S.

1993-04-01

Mesozoic polyphase contractile and superposed ductile extensional structures affect Proterozoic augen gneiss, Paleozoic metasedimentary rocks, and Jurassic granitoids in the Boyer Gap area of the northern Dome Rock Mtns, W-central Arizona. The nappe-style contractile structures are preserved in the footwall of the Tyson Thrust shear zone, which is one of the structurally lowest thrust faults in the E-trending Jurassic and Cretaceous Maria fold and thrust belt. Contractile deformation preceded emplacement of Late Cretaceous granite (ca 80 Ma, U-Pb zircon) and some may be older than variably deformed Late Jurassic leucogranite. Specifically, detailed structural mapping reveals the presence of a km-scalemore » antiformal syncline that apparently formed as a result of superposition of tight to isoclinal, south-facing folds on an earlier, north-facing recumbent fold. The stratigraphic sequence of metamorphosed Paleozoic cratonal strata is largely intact in the northern Dome Rock Mtns, such that overturned and upright stratigraphic units can be distinguished. A third phase of folding in the Boyer Gap area is distinguished by intersection lineations that are folded obliquely across the hinges of open to tight, sheath folds. The axial planes of the sheet folds are subparallel to the mylonitic foliation in top-to-the-northeast extensional shear zones. The timing of ductile extensional structures in the northern Dome Rock is constrained by [sup 40]Ar/[sup 39]Ar isochron ages of 56 Ma and 48 Ma on biotite from mylonitic rocks in both the hanging wall and footwall of the Tyson Thrust shear zone. The two early phases of folding are the dominant mechanism by which shortening was accommodated in the Boyer Gap area, as opposed to deformation along discrete thrust faults with large offset. All of the ductile extensional structures are spectacularly displayed at an outcrop scale but are not of sufficient magnitude to obliterate the km-scale Mesozoic polyphase contractile structures.« less

The Dynameomics Entropy Dictionary: A Large-Scale Assessment of Conformational Entropy across Protein Fold Space.

PubMed

Towse, Clare-Louise; Akke, Mikael; Daggett, Valerie

2017-04-27

Molecular dynamics (MD) simulations contain considerable information with regard to the motions and fluctuations of a protein, the magnitude of which can be used to estimate conformational entropy. Here we survey conformational entropy across protein fold space using the Dynameomics database, which represents the largest existing data set of protein MD simulations for representatives of essentially all known protein folds. We provide an overview of MD-derived entropies accounting for all possible degrees of dihedral freedom on an unprecedented scale. Although different side chains might be expected to impose varying restrictions on the conformational space that the backbone can sample, we found that the backbone entropy and side chain size are not strictly coupled. An outcome of these analyses is the Dynameomics Entropy Dictionary, the contents of which have been compared with entropies derived by other theoretical approaches and experiment. As might be expected, the conformational entropies scale linearly with the number of residues, demonstrating that conformational entropy is an extensive property of proteins. The calculated conformational entropies of folding agree well with previous estimates. Detailed analysis of specific cases identifies deviations in conformational entropy from the average values that highlight how conformational entropy varies with sequence, secondary structure, and tertiary fold. Notably, α-helices have lower entropy on average than do β-sheets, and both are lower than coil regions.

Exploring the folding free energy landscape of insulin using bias exchange metadynamics.

PubMed

Todorova, Nevena; Marinelli, Fabrizio; Piana, Stefano; Yarovsky, Irene

2009-03-19

The bias exchange metadynamics (BE-META) technique was applied to investigate the folding mechanism of insulin, one of the most studied and biologically important proteins. The BE-META simulations were performed starting from an extended conformation of chain B of insulin, using only eight replicas and seven reaction coordinates. The folded state, together with the intermediate states along the folding pathway were identified and their free energy was determined. Three main basins were found separated from one another by a large free energy barrier. The characteristic native fold of chain B was observed in one basin, while the other two most populated basins contained "molten-globule" conformations stabilized by electrostatic and hydrophobic interactions, respectively. Transitions between the three basins occur on the microsecond time scale. The implications and relevance of this finding to the folding mechanisms of insulin were investigated.

Statistical properties of a folded elastic rod

NASA Astrophysics Data System (ADS)

Bayart, Elsa; Deboeuf, Stéphanie; Boué, Laurent; Corson, Francis; Boudaoud, Arezki; Adda-Bedia, Mokhtar

2010-03-01

A large variety of elastic structures naturally seem to be confined into environments too small to accommodate them; the geometry of folded structures span a wide range of length-scales. The elastic properties of these confined systems are further constrained by self-avoidance as well as by the dimensionality of both structures and container. To mimic crumpled paper, we devised an experimental setup to study the packing of a dimensional elastic object in 2D geometries: an elastic rod is folded at the center of a circular Hele-Shaw cell by a centripetal force. The initial configuration of the rod and the acceleration of the rotating disk allow to span different final folded configurations while the final rotation speed controls the packing intensity. Using image analysis we measure geometrical and mechanical properties of the folded configurations, focusing on length, curvature and energy distributions.

Multiple-basin energy landscapes for large-amplitude conformational motions of proteins: Structure-based molecular dynamics simulations

PubMed Central

Okazaki, Kei-ichi; Koga, Nobuyasu; Takada, Shoji; Onuchic, Jose N.; Wolynes, Peter G.

2006-01-01

Biomolecules often undergo large-amplitude motions when they bind or release other molecules. Unlike macroscopic machines, these biomolecular machines can partially disassemble (unfold) and then reassemble (fold) during such transitions. Here we put forward a minimal structure-based model, the “multiple-basin model,” that can directly be used for molecular dynamics simulation of even very large biomolecular systems so long as the endpoints of the conformational change are known. We investigate the model by simulating large-scale motions of four proteins: glutamine-binding protein, S100A6, dihydrofolate reductase, and HIV-1 protease. The mechanisms of conformational transition depend on the protein basin topologies and change with temperature near the folding transition. The conformational transition rate varies linearly with driving force over a fairly large range. This linearity appears to be a consequence of partial unfolding during the conformational transition. PMID:16877541

Protein homology model refinement by large-scale energy optimization.

PubMed

Park, Hahnbeom; Ovchinnikov, Sergey; Kim, David E; DiMaio, Frank; Baker, David

2018-03-20

Proteins fold to their lowest free-energy structures, and hence the most straightforward way to increase the accuracy of a partially incorrect protein structure model is to search for the lowest-energy nearby structure. This direct approach has met with little success for two reasons: first, energy function inaccuracies can lead to false energy minima, resulting in model degradation rather than improvement; and second, even with an accurate energy function, the search problem is formidable because the energy only drops considerably in the immediate vicinity of the global minimum, and there are a very large number of degrees of freedom. Here we describe a large-scale energy optimization-based refinement method that incorporates advances in both search and energy function accuracy that can substantially improve the accuracy of low-resolution homology models. The method refined low-resolution homology models into correct folds for 50 of 84 diverse protein families and generated improved models in recent blind structure prediction experiments. Analyses of the basis for these improvements reveal contributions from both the improvements in conformational sampling techniques and the energy function.

High throughput profile-profile based fold recognition for the entire human proteome.

PubMed

McGuffin, Liam J; Smith, Richard T; Bryson, Kevin; Sørensen, Søren-Aksel; Jones, David T

2006-06-07

In order to maintain the most comprehensive structural annotation databases we must carry out regular updates for each proteome using the latest profile-profile fold recognition methods. The ability to carry out these updates on demand is necessary to keep pace with the regular updates of sequence and structure databases. Providing the highest quality structural models requires the most intensive profile-profile fold recognition methods running with the very latest available sequence databases and fold libraries. However, running these methods on such a regular basis for every sequenced proteome requires large amounts of processing power. In this paper we describe and benchmark the JYDE (Job Yield Distribution Environment) system, which is a meta-scheduler designed to work above cluster schedulers, such as Sun Grid Engine (SGE) or Condor. We demonstrate the ability of JYDE to distribute the load of genomic-scale fold recognition across multiple independent Grid domains. We use the most recent profile-profile version of our mGenTHREADER software in order to annotate the latest version of the Human proteome against the latest sequence and structure databases in as short a time as possible. We show that our JYDE system is able to scale to large numbers of intensive fold recognition jobs running across several independent computer clusters. Using our JYDE system we have been able to annotate 99.9% of the protein sequences within the Human proteome in less than 24 hours, by harnessing over 500 CPUs from 3 independent Grid domains. This study clearly demonstrates the feasibility of carrying out on demand high quality structural annotations for the proteomes of major eukaryotic organisms. Specifically, we have shown that it is now possible to provide complete regular updates of profile-profile based fold recognition models for entire eukaryotic proteomes, through the use of Grid middleware such as JYDE.

Influences of Brain Size, Sex, and Sex Chromosome Complement on the Architecture of Human Cortical Folding.

PubMed

Fish, Ari M; Cachia, Arnaud; Fischer, Clara; Mankiw, Catherine; Reardon, P K; Clasen, Liv S; Blumenthal, Jonathan D; Greenstein, Deanna; Giedd, Jay N; Mangin, Jean-François; Raznahan, Armin

2017-12-01

Gyrification is a fundamental property of the human cortex that is increasingly studied by basic and clinical neuroscience. However, it remains unclear if and how the global architecture of cortical folding varies with 3 interwoven sources of anatomical variation: brain size, sex, and sex chromosome dosage (SCD). Here, for 375 individuals spanning 7 karyotype groups (XX, XY, XXX, XYY, XXY, XXYY, XXXXY), we use structural neuroimaging to measure a global sulcation index (SI, total sulcal/cortical hull area) and both determinants of sulcal area: total sulcal length and mean sulcal depth. We detail large and patterned effects of sex and SCD across all folding metrics, but show that these effects are in fact largely consistent with the normative scaling of cortical folding in health: larger human brains have disproportionately high SI due to a relative expansion of sulcal area versus hull area, which arises because disproportionate sulcal lengthening overcomes a lack of proportionate sulcal deepening. Accounting for these normative allometries reveals 1) brain size-independent sulcal lengthening in males versus females, and 2) insensitivity of overall folding architecture to SCD. Our methodology and findings provide a novel context for future studies of human cortical folding in health and disease. Published by Oxford University Press 2016.

Botulinum toxin in the treatment of vocal fold nodules.

PubMed

Allen, Jacqui E; Belafsky, Peter C

2009-12-01

Promising new techniques in the management of vocal fold nodules have been developed in the past 2 years. Simultaneously, the therapeutic use of botulinum toxin has rapidly expanded. This review explores the use of botulinum toxin in treatment of vocal nodules and summarizes current therapeutic concepts. New microsurgical instruments and techniques, refinements in laser technology, radiosurgical excision and steroid intralesional injections are all promising new techniques in the management of vocal nodules. Botulinum toxin-induced 'voice rest' is a new technique we have employed in patients with recalcitrant nodules. Successful resolution of nodules is possible with this technique, without the risk of vocal fold scarring inherent in dissection/excision techniques. Botulinum toxin usage is exponentially increasing, and large-scale, long-term studies demonstrate its safety profile. Targeted vocal fold temporary paralysis induced by botulinum toxin injection is a new, well tolerated and efficacious treatment in patients with persistent vocal fold nodules.

Evolutionary trend toward kinetic stability in the folding trajectory of RNases H

PubMed Central

Lim, Shion A.; Hart, Kathryn M.; Marqusee, Susan

2016-01-01

Proper folding of proteins is critical to producing the biological machinery essential for cellular function. The rates and energetics of a protein’s folding process, which is described by its energy landscape, are encoded in the amino acid sequence. Over the course of evolution, this landscape must be maintained such that the protein folds and remains folded over a biologically relevant time scale. How exactly a protein’s energy landscape is maintained or altered throughout evolution is unclear. To study how a protein’s energy landscape changed over time, we characterized the folding trajectories of ancestral proteins of the ribonuclease H (RNase H) family using ancestral sequence reconstruction to access the evolutionary history between RNases H from mesophilic and thermophilic bacteria. We found that despite large sequence divergence, the overall folding pathway is conserved over billions of years of evolution. There are robust trends in the rates of protein folding and unfolding; both modern RNases H evolved to be more kinetically stable than their most recent common ancestor. Finally, our study demonstrates how a partially folded intermediate provides a readily adaptable folding landscape by allowing the independent tuning of kinetics and thermodynamics. PMID:27799545

Origin of intraformational folds in the Jurassic Todilto Limestone, Ambrosia Lake uranium mining district, McKinley and Valencia counties, New Mexico

USGS Publications Warehouse

Green, M.W.

1982-01-01

The Todilto Limestone of Middle Jurassic age in the Ambrosia Lake uranium mining district of McKinley and Valencia Counties, New Mexico, is the host formation for numerous small- to medium-sized uranium deposits in joints, shear zones, and fractures within small- to large-scale intraformational folds. The folds probably were formed as a result of differential sediment loading when eolian sand dunes of the overlying Summerville Formation of Middle Jurassic age migrated over soft, chemically precipitated, lime muds of the Todilto shortly after their deposition in a regressive, mixed fresh and saline lacustrine or marine environment of deposition. Encroachment of Summerville eolian dunes over soft Todilto lime muds was apparently a local phenomenon and was restricted to postulated beltlike zones which trended radially across the Todilto coastline toward the receding body of water. Intraformational folding is believed to be confined to the pathways of individual eolian dunes or clusters of dunes within the dune belts. During the process of sediment loading by migrating sand dunes, layers of Todilto lime mud were differentially compacted, contorted, and dewatered, producing both small- and large-scale plastic deformation structures, including convolute laminations, mounds, rolls, folds, and small anticlines and synclines. With continued compaction and dewatering, the mud, in localized areas, reached a point of desaturation at which sediment plasticity was lost. Prolonged loading by overlying dune sands thus caused faulting, shearing, fracturing, and jointing of contorted limestone beds. These areas or zones of deformation within the limestone became the preferred sites of epigenetic uranium mineralization because of the induced transmissivity created by sediment rupture. Along most of the prograding Todilto coastline, adjacent to the eolian dune belts, both interdune and coastal sabkha environments dominated during Todilto-Summerville time. Sediments in coastal areas consisted mainly of clay, silt, sandy silt, and very fine-grained sand, which was apparently derived from the winnowing of the finer grained fraction of sediment from adjacent dune fields during periods of eolian activity. Most of the sabkha sediments were probably carried in airborne suspension to the low-lying, ground-water-saturated coastal areas, where they were deposited as relatively uniform blanket-like layers. Deposition of sabkha deposits was apparently slow and uniform over most of the Todilto coastal areas and crested only small-scale deformation features in underlying Todilto rocks. Large-scale deformation features and uranium deposits are both notably absent in the Todilto where it is overlain by finer textured sabkha deposits in the Summerville.

Martian Polar Caps: Folding, Faulting, Flowing Glaciers of Multiple Interbedded Ices

NASA Astrophysics Data System (ADS)

Kargel, J. S.

2001-12-01

The Martian south polar cap (permanent CO2 cap and polar layered deposits), exhibit abundant, varied, and widespread deformational phenomena. Folding and boudinage are very common. Strike-slip or normal faults are rarer. Common in the vicinity of major troughs and scarps are signs of convergent flow tectonics manifested as wrinkle-ridge-like surface folds, thrust faults, and viscous forebulges with thin-skinned extensional crevasses and wrinkle-ridge folds. Such flow convergence is predicted by theory. Boudinage and folding at the 300-m wavelength scale, indicating rheologically contrasting materials, is widely exposed at deep levels along erosional scarps. Independent morphologic evidence indicates south polar materials of contrasting volatility. Hence, the south polar cap appears to be a multiphase structure of interbedded ices. The north polar cap locally also exhibits flow indicators, though they are neither as common nor as varied as in the south. The large-scale quasi-spiral structure of the polar caps could be a manifestation of large-scale boudinage. According to this scenario, deep-level boudinage continuously originates under the glacial divide (the polar cap summit). Rod-like boudin structures are oriented transverse to flow and migrate outward with the large-scale flow field. Troughs develop over areas between major boudins. A dynamic competition, and possibly a rough balance, develops between the local flow field in the vicinity of a trough (which tends to close the trough by lateral closure and upwelling flow) and sublimation erosion (which tends to widen and deepen them). Over time, the troughs flow to the margins of the polar cap where they, along with other polar structures, are destroyed by sublimation. Major ice types contributing to rheological and volatility layering may include, in order of highest to lowest mechanical strength, CO2 clathrate hydrate, water ice containing inert/insoluble dust, pure water ice, water ice containing traces of liquid-soluble salts, water ice containing traces of solid-soluble acids, CO2 ice. This is also nearly the same sequence of highest to lowest melting/dissociation points, but it is different than the sequence of volatility. This geologic-structural interpretation and specific chemical models are amenable to testing by computational means and point the way toward future needed observations, including complete high-resolution imaging of the polar caps, measurement of flow fields (possibly by laser interferometry), mapping of subsurface structures (by radar and/or seismic methods), and determination of composition (by penetrators, drillers, or borers). New lab data are needed on the physical properties of candidate ices.

Large Scale Expansion of Human Umbilical Cord Cells in a Rotating Bed System Bioreactor for Cardiovascular Tissue Engineering Applications

PubMed Central

Reichardt, Anne; Polchow, Bianca; Shakibaei, Mehdi; Henrich, Wolfgang; Hetzer, Roland; Lueders, Cora

2013-01-01

Widespread use of human umbilical cord cells for cardiovascular tissue engineering requires production of large numbers of well-characterized cells under controlled conditions. In current research projects, the expansion of cells to be used to create a tissue construct is usually performed in static cell culture systems which are, however, often not satisfactory due to limitations in nutrient and oxygen supply. To overcome these limitations dynamic cell expansion in bioreactor systems under controllable conditions could be an important tool providing continuous perfusion for the generation of large numbers of viable pre-conditioned cells in a short time period. For this purpose cells derived from human umbilical cord arteries were expanded in a rotating bed system bioreactor for up to 9 days. For a comparative study, cells were cultivated under static conditions in standard culture devices. Our results demonstrated that the microenvironment in the perfusion bioreactor was more favorable than that of the standard cell culture flasks. Data suggested that cells in the bioreactor expanded 39 fold (38.7 ± 6.1 fold) in comparison to statically cultured cells (31.8 ± 3.0 fold). Large-scale production of cells in the bioreactor resulted in more than 3 x 108 cells from a single umbilical cord fragment within 9 days. Furthermore cell doubling time was lower in the bioreactor system and production of extracellular matrix components was higher. With this study, we present an appropriate method to expand human umbilical cord artery derived cells with high cellular proliferation rates in a well-defined bioreactor system under GMP conditions. PMID:23847691

Interpreting whether isoclinal folds are antiforms or synforms using FIA succession

NASA Astrophysics Data System (ADS)

Cao, H.

2012-12-01

Using the asymmetries of the overprinting foliations preserved as inclusion trails that define the FIAs to investigate whether an enigmatic isoclinal fold in the region is an antiform or synform. This approach also reveals when the fold first formed during the tectonic history of the region. Multiply deformed and isoclinally folded interlayered high metamorphic grade gneisses and schists can be very difficult rocks for resolving early formed stratigraphic and structural relationships. When such rocks contain porphyroblasts a new approach is possible because of the way in which porphyroblast growth is affected by crenulation versus reactivation of compositional layering (Bell et al., 2003). Isoclinally folded rocks in the Arkansas River region of South Central Colorado contain relics of fold hinges that have been very difficult to ascertain whether they are antiforms or synforms because of younger refolding effects and the locally truncated nature of coarse compositional layering. With the realization that rocks with a schistosity parallel to bedding (S0 parallel S1) have undergone lengthy histories of deformation that predate the obvious first deformation (e.g. Bell et al., 2003; Sayab, 2006; Yeh, 2007) came recognition that large scale regional folds can form early during this process and be preserved throughout orogenesis (e.g., Ham and Bell, 2004; Bell and Newman, 2006. This extensive history is lost within the matrix because of reactivational shear on the compositional layering (Bell et al., 1998, 2003, 2004, 2005; Ham and Bell, 2004). However, it can be extracted by measuring FIAs. Recent work using this approach has revealed that the trends of axial planes of all map scale folds, when plotted on a rose diagram, strikingly reflect the FIA trends (e.g., Sanislav, 2009; Shah, 2009). That is, although it was demonstrated by Bell et al. (2003) that the largest scale regional folds commonly form early in the total history, other folds can form and be preserved from subsequent destruction in the strain shadows of plutons or through the partitioning of deformation due to heterogeneities at depth.

The Fold Analysis Challenge: A virtual globe-based educational resource

NASA Astrophysics Data System (ADS)

De Paor, Declan G.; Dordevic, Mladen M.; Karabinos, Paul; Tewksbury, Barbara J.; Whitmeyer, Steven J.

2016-04-01

We present an undergraduate structural geology laboratory exercise using the Google Earth virtual globe with COLLADA models, optionally including an interactive stereographic projection and JavaScript controls. The learning resource challenges students to identify bedding traces and estimate bedding orientation at several locations on a fold, to fit the fold axis and axial plane to stereographic projection data, and to fit a doubly-plunging fold model to the large-scale structure. The chosen fold is the Sheep Mountain Anticline, a Laramide uplift in the Big Horn Basin of Wyoming. We take an education research-based approach, guiding students through three levels of difficulty. The exercise aims to counter common student misconceptions and stumbling blocks regarding penetrative structures. It can be used in preparation for an in-person field trip, for post-trip reinforcement, or as a virtual field experience in an online-only course. Our KML scripts can be easily transferred to other fold structures around the globe.

Fabric changes and their influence on P-wave velocity patterns—examples from a polyphase deformed orthogneiss

NASA Astrophysics Data System (ADS)

Siegesmund, S.; Vollbrecht, A.; Pros, Z.

1993-10-01

The complete P-wave velocity distribution, preferred orientation of rock-forming minerals and microcracks of two differently deformed orthogneisses from the Kutna Hora Crystalline Unit were investigated. The complete symmetry of P-wave velocities were determined as a function of confining pressure on the basis of 132 independent propagation directions up to 400 MPa. The two samples are of almost identical mineralogical composition, but exhibit different fabrics which can be related to different positions within a large-scale fold structure. The symmetry of the Vp-diagrams change from nearly transversely isotropic for the sample from the limb area to orthorhombic for the sample from the hinge zone, which shows an additional crenulation cleavage. This change of symmetry is observed at all pressure levels. Reorientation of the main velocity directions ( Vpmin, Vpmax, Kpint) between hinge and limb is controlled by the microcrack fabric and the texture of the rock-forming minerals. This can cause significant differences in reflectivity related to fabric changes within large-scale folds.

Coexistence of Native and Denatured Phases in a Single Proteinlike Molecule

NASA Astrophysics Data System (ADS)

Du, Rose; Grosberg, Alexander Yu.; Tanaka, Toyoichi

1999-11-01

In order to understand the nuclei which develop during the course of protein folding and unfolding, we examine equilibrium coexistence of phases within a single heteropolymer chain. We computationally generate the phase segregation by applying a ``folding pressure,'' or adding an energetic bonus for native monomer-monomer contacts. The computer models reveal that in a polymer system some nuclei hinder folding via topological constraints. Using this insight, we show that the critical nucleus size is of the order of the entire chain and that unfolding time scales as exp\\(cN2/3\\), in the large N limit, N and c being the chain length and a constant, respectively.

Self-folding and aggregation of amyloid nanofibrils

NASA Astrophysics Data System (ADS)

Paparcone, Raffaella; Cranford, Steven W.; Buehler, Markus J.

2011-04-01

Amyloids are highly organized protein filaments, rich in β-sheet secondary structures that self-assemble to form dense plaques in brain tissues affected by severe neurodegenerative disorders (e.g. Alzheimer's Disease). Identified as natural functional materials in bacteria, in addition to their remarkable mechanical properties, amyloids have also been proposed as a platform for novel biomaterials in nanotechnology applications including nanowires, liquid crystals, scaffolds and thin films. Despite recent progress in understanding amyloid structure and behavior, the latent self-assembly mechanism and the underlying adhesion forces that drive the aggregation process remain poorly understood. On the basis of previous full atomistic simulations, here we report a simple coarse-grain model to analyze the competition between adhesive forces and elastic deformation of amyloid fibrils. We use simple model system to investigate self-assembly mechanisms of fibrils, focused on the formation of self-folded nanorackets and nanorings, and thereby address a critical issue in linking the biochemical (Angstrom) to micrometre scales relevant for larger-scale states of functional amyloid materials. We investigate the effect of varying the interfibril adhesion energy on the structure and stability of self-folded nanorackets and nanorings and demonstrate that these aggregated amyloid fibrils are stable in such states even when the fibril-fibril interaction is relatively weak, given that the constituting amyloid fibril length exceeds a critical fibril length-scale of several hundred nanometres. We further present a simple approach to directly determine the interfibril adhesion strength from geometric measures. In addition to providing insight into the physics of aggregation of amyloid fibrils our model enables the analysis of large-scale amyloid plaques and presents a new method for the estimation and engineering of the adhesive forces responsible of the self-assembly process of amyloidnanostructures, filling a gap that previously existed between full atomistic simulations of primarily ultra-short fibrils and much larger micrometre-scale amyloid aggregates. Via direct simulation of large-scale amyloid aggregates consisting of hundreds of fibrils we demonstrate that the fibril length has a profound impact on their structure and mechanical properties, where the critical fibril length-scale derived from our analysis of self-folded nanorackets and nanorings defines the structure of amyloid aggregates. A multi-scale modeling approach as used here, bridging the scales from Angstroms to micrometres, opens a wide range of possible nanotechnology applications by presenting a holistic framework that balances mechanical properties of individual fibrils, hierarchical self-assembly, and the adhesive forces determining their stability to facilitate the design of de novoamyloid materials.

The geometry of folds in granitoid rocks of northeastern Alberta

NASA Astrophysics Data System (ADS)

Willem Langenberg, C.; Ramsden, John

1980-06-01

Granitoid rocks which predominate in the Precambrian shield of northeastern Alberta show large-scale fold structures. A numerical procedure has been used to obtain modal foliation orientations. This procedure results in the smoothing of folded surfaces that show roughness on a detailed scale. Statistical tests are used to divide the study areas into cylindrical domains. Structural sections can be obtained for each domain, and horizontal and vertical sections are used to construct block diagrams. The projections are performed numerically and plotted by computer. This method permits blocks to be viewed from every possible angle. Both perspective and orthographic projections can be produced. The geometries of a dome in the Tulip Lake area and a synform in the Hooker Lake area have been obtained. The domal structure is compared with polyphase deformational interference patterns and with experimental diapiric structures obtained in a centrifuge system. The synform in the Hooker Lake area may be genetically related to the doming in the Tulip Lake area.

Exploring the protein folding free energy landscape: coupling replica exchange method with P3ME/RESPA algorithm.

PubMed

Zhou, Ruhong

2004-05-01

A highly parallel replica exchange method (REM) that couples with a newly developed molecular dynamics algorithm particle-particle particle-mesh Ewald (P3ME)/RESPA has been proposed for efficient sampling of protein folding free energy landscape. The algorithm is then applied to two separate protein systems, beta-hairpin and a designed protein Trp-cage. The all-atom OPLSAA force field with an explicit solvent model is used for both protein folding simulations. Up to 64 replicas of solvated protein systems are simulated in parallel over a wide range of temperatures. The combined trajectories in temperature and configurational space allow a replica to overcome free energy barriers present at low temperatures. These large scale simulations reveal detailed results on folding mechanisms, intermediate state structures, thermodynamic properties and the temperature dependences for both protein systems.

Comparison of an algebraic multigrid algorithm to two iterative solvers used for modeling ground water flow and transport

USGS Publications Warehouse

Detwiler, R.L.; Mehl, S.; Rajaram, H.; Cheung, W.W.

2002-01-01

Numerical solution of large-scale ground water flow and transport problems is often constrained by the convergence behavior of the iterative solvers used to solve the resulting systems of equations. We demonstrate the ability of an algebraic multigrid algorithm (AMG) to efficiently solve the large, sparse systems of equations that result from computational models of ground water flow and transport in large and complex domains. Unlike geometric multigrid methods, this algorithm is applicable to problems in complex flow geometries, such as those encountered in pore-scale modeling of two-phase flow and transport. We integrated AMG into MODFLOW 2000 to compare two- and three-dimensional flow simulations using AMG to simulations using PCG2, a preconditioned conjugate gradient solver that uses the modified incomplete Cholesky preconditioner and is included with MODFLOW 2000. CPU times required for convergence with AMG were up to 140 times faster than those for PCG2. The cost of this increased speed was up to a nine-fold increase in required random access memory (RAM) for the three-dimensional problems and up to a four-fold increase in required RAM for the two-dimensional problems. We also compared two-dimensional numerical simulations of steady-state transport using AMG and the generalized minimum residual method with an incomplete LU-decomposition preconditioner. For these transport simulations, AMG yielded increased speeds of up to 17 times with only a 20% increase in required RAM. The ability of AMG to solve flow and transport problems in large, complex flow systems and its ready availability make it an ideal solver for use in both field-scale and pore-scale modeling.

Transpressional folding and associated cross-fold jointing controlling the geometry of post-orogenic vein-type W-Sn mineralization: examples from Minas da Panasqueira, Portugal

NASA Astrophysics Data System (ADS)

Jacques, Dominique; Vieira, Romeu; Muchez, Philippe; Sintubin, Manuel

2018-02-01

The world-class W-Sn Panasqueira deposit consists of an extensive, subhorizontal vein swarm, peripheral to a late-orogenic greisen cupola. The vein swarm consists of hundreds of co-planar quartz veins that are overlapping and connected laterally over large distances. Various segmentation structures, a local zigzag geometry, and the occurrence of straight propagation paths indicate that they exploited a regional joint system. A detailed orientation analysis of the systematic joints reveals a geometrical relationship with the subvertical F2 fold generation, reflecting late-Variscan transpression. The joints are consistently orthogonal to the steeply plunging S0-S2 intersection lineation, both on the regional and the outcrop scale, and are thus defined as cross-fold or ac-joints. The joint system developed during the waning stages of the Variscan orogeny, when already uplifted to an upper-crustal level. Veining reactivated these cross-fold joints under the conditions of hydraulic overpressures and low differential stress. The consistent subperpendicular orientation of the veins relative to the non-cylindrical F2 hinge lines, also when having an inclined attitude, demonstrates that veining did not occur during far-field horizontal compression. Vein orientation is determined by local stress states variable on a meter-scale but with the minimum principal stress consistently subparallel to fold hinge lines. The conspicuous subhorizontal attitude of the Panasqueira vein swarm is thus dictated by the geometry of late-orogenic folds, which developed synchronous with oroclinal buckling of the Ibero-Armorican arc.

Superposed buckle folding in the eastern Iberian Chain, Spain

NASA Astrophysics Data System (ADS)

Simón, José L.

2004-08-01

The Aliaga area (eastern Iberian Chain) shows large-scale examples of buckle superposition developed during Tertiary folding. In most cases, ENE-trending folds overprint earlier NNW-SSE-trending ones. The resulting structures are mapped, analysed, and genetically classified by comparison with analogue models described by several authors. The following types are found: standard Type 1 (1a: dome-and-basin structure, 1b: unequal-wavelength overprinted folds); modified Type 1 (1c: T-shaped 'joined' folds; 1d: T-shaped 'abutting' folds; 1e: L-shaped folds; 1f: 'snake-like' folds); standard Type 2 (2a: non-cylindrical buckling of earlier axial surfaces involving hinge replacement). Different superposed sets of flexural-slip striations record successive folding episodes in snake-like folds, and hinge replacement in the case of Type 2a superpositions. Types 1 and 2 apparently develop where the earlier folds have interlimb angles over and below 90°, respectively, which fits the results of analogue modelling and theoretical analysis by previous authors. Types 1b and 1d are associated with higher W1/W2 wavelength ratios than Types 1a and 1c. Other controlling factors are viscosity contrast and erosion processes. Specifically, erosion of competent limestone beds in the hinge zone of a NNW-SSE-trending anticline allowed the near-vertical eastern limb to be refolded into snake-like folds.

Tertiary deformation and metamorphism SE of Tibet: The folded Tiger-leap décollement of NW Yunnan, China

NASA Astrophysics Data System (ADS)

Lacassin, Robin; SchäRer, Urs; Leloup, P. Hervé; Arnaud, Nicolas; Tapponnier, Paul; Liu, Xiaohan; Zhang, Liansheng

1996-06-01

The Yulong-Haba Xue Shan range, in the northwestern part of Yunnan (China), is a large N-S antiform that folds the Paleozoic series of the Yangzi platform. The upper Yangzi River (Jinsha Jiang) has cut a 3500 m-deep valley (Hu Tiao gorge) across this antiform, thus exposing folded, bedding-parallel, ductile shear zones (décollements), with transport toward the SSW (in the present geographical coordinates). The large finite shear strain implies tens of kilometers of transport, pointing to the regional significance of these décollements. Rb/Sr radiometric dating of phlogopites that crystallized in marbles within the foliation planes yields the age of the metamorphic and deformation event (35.9 ± 0.3 (2σ) Ma). The age derives from an internal Rb-Sr isochron, made on different size fractions of the same mineral, which provides a novel demonstration of the feasibility of such plots. Transport on the décollement and related shortening occurred prior to, or at the onset of, extrusion of Indochina along the Ailao Shan-Red River shear zone, ≈80 km west of the Yulong Shan. The 39Ar/40Ar age spectra of K-feldspar from the core of the Yulong Shan suggest uplift by antiformal folding around 17 Ma, as Indochina's extrusion came to an end. We infer that other large-scale Cenozoic décollements such as that exhumed in the Yulong Shan underlie some of the vast, folded areas that surround the eastern Himalayan syntaxis. Transport on such décollements, first toward the south and then toward the east, and folding above them, might have occurred during two principal shortening phases, whose ages bracket Indochina's escape toward the SE.

Structure of small-scale magnetic fields in the kinematic dynamo theory.

PubMed

Schekochihin, Alexander; Cowley, Steven; Maron, Jason; Malyshkin, Leonid

2002-01-01

A weak fluctuating magnetic field embedded into a a turbulent conducting medium grows exponentially while its characteristic scale decays. In the interstellar medium and protogalactic plasmas, the magnetic Prandtl number is very large, so a broad spectrum of growing magnetic fluctuations is excited at small (subviscous) scales. The condition for the onset of nonlinear back reaction depends on the structure of the field lines. We study the statistical correlations that are set up in the field pattern and show that the magnetic-field lines possess a folding structure, where most of the scale decrease is due to the field variation across itself (rapid transverse direction reversals), while the scale of the field variation along itself stays approximately constant. Specifically, we find that, though both the magnetic energy and the mean-square curvature of the field lines grow exponentially, the field strength and the field-line curvature are anticorrelated, i.e., the curved field is relatively weak, while the growing field is relatively flat. The detailed analysis of the statistics of the curvature shows that it possesses a stationary limiting distribution with the bulk located at the values of curvature comparable to the characteristic wave number of the velocity field and a power tail extending to large values of curvature where it is eventually cut off by the resistive regularization. The regions of large curvature, therefore, occupy only a small fraction of the total volume of the system. Our theoretical results are corroborated by direct numerical simulations. The implication of the folding effect is that the advent of the Lorentz back reaction occurs when the magnetic energy approaches that of the smallest turbulent eddies. Our results also directly apply to the problem of statistical geometry of the material lines in a random flow.

The Death Valley turtlebacks reinterpreted as Miocene­ Pliocene folds of a major detachment surface

USGS Publications Warehouse

Holm, Daniel K.; Fleck, Robert J.; Lux, Daniel R.

1994-01-01

Determining the origin of extension parallel folds in metamorphic core complexes is fundamental to understanding the development of detachment faults. An excellent example of such a feature occurs in the Death Valley region of California where a major, undulatory, detachment fault is exposed along the well-known turtleback (antiformal) surfaces of the Black Mountains. In the hanging wall of this detachment fault are deformed strata of the Copper Canyon Formation. New age constraints indicate that the Copper Canyon Formation was deposited from ~6 to 3 Ma. The formation was folded during deposition into a SE-plunging syncline with an axial surface coplanar with that of a synform in the underlying detachment. This relation suggests the turtlebacks are a folded detachment surface formed during large-scale extension in an overall constrictional strain field. The present, more planar, Black Mountains frontal fault system may be the result of out-stepping of a normal fault system away from an older detachment fault that was deactivated by folding.

Nanoliter-Scale Protein Crystallization and Screening with a Microfluidic Droplet Robot

PubMed Central

Zhu, Ying; Zhu, Li-Na; Guo, Rui; Cui, Heng-Jun; Ye, Sheng; Fang, Qun

2014-01-01

Large-scale screening of hundreds or even thousands of crystallization conditions while with low sample consumption is in urgent need, in current structural biology research. Here we describe a fully-automated droplet robot for nanoliter-scale crystallization screening that combines the advantages of both automated robotics technique for protein crystallization screening and the droplet-based microfluidic technique. A semi-contact dispensing method was developed to achieve flexible, programmable and reliable liquid-handling operations for nanoliter-scale protein crystallization experiments. We applied the droplet robot in large-scale screening of crystallization conditions of five soluble proteins and one membrane protein with 35–96 different crystallization conditions, study of volume effects on protein crystallization, and determination of phase diagrams of two proteins. The volume for each droplet reactor is only ca. 4–8 nL. The protein consumption significantly reduces 50–500 fold compared with current crystallization stations. PMID:24854085

Nanoliter-scale protein crystallization and screening with a microfluidic droplet robot.

PubMed

Zhu, Ying; Zhu, Li-Na; Guo, Rui; Cui, Heng-Jun; Ye, Sheng; Fang, Qun

2014-05-23

Large-scale screening of hundreds or even thousands of crystallization conditions while with low sample consumption is in urgent need, in current structural biology research. Here we describe a fully-automated droplet robot for nanoliter-scale crystallization screening that combines the advantages of both automated robotics technique for protein crystallization screening and the droplet-based microfluidic technique. A semi-contact dispensing method was developed to achieve flexible, programmable and reliable liquid-handling operations for nanoliter-scale protein crystallization experiments. We applied the droplet robot in large-scale screening of crystallization conditions of five soluble proteins and one membrane protein with 35-96 different crystallization conditions, study of volume effects on protein crystallization, and determination of phase diagrams of two proteins. The volume for each droplet reactor is only ca. 4-8 nL. The protein consumption significantly reduces 50-500 fold compared with current crystallization stations.

Discrete domains of gene expression in germinal layers distinguish the development of gyrencephaly

PubMed Central

de Juan Romero, Camino; Bruder, Carl; Tomasello, Ugo; Sanz-Anquela, José Miguel; Borrell, Víctor

2015-01-01

Gyrencephalic species develop folds in the cerebral cortex in a stereotypic manner, but the genetic mechanisms underlying this patterning process are unknown. We present a large-scale transcriptomic analysis of individual germinal layers in the developing cortex of the gyrencephalic ferret, comparing between regions prospective of fold and fissure. We find unique transcriptional signatures in each germinal compartment, where thousands of genes are differentially expressed between regions, including ∼80% of genes mutated in human cortical malformations. These regional differences emerge from the existence of discrete domains of gene expression, which occur at multiple locations across the developing cortex of ferret and human, but not the lissencephalic mouse. Complex expression patterns emerge late during development and map the eventual location of folds or fissures. Protomaps of gene expression within germinal layers may contribute to define cortical folds or functional areas, but our findings demonstrate that they distinguish the development of gyrencephalic cortices. PMID:25916825

Unsteady flow motions in the supraglottal region during phonation

NASA Astrophysics Data System (ADS)

Luo, Haoxiang; Dai, Hu

2008-11-01

The highly unsteady flow motions in the larynx are not only responsible for producing the fundamental frequency tone in phonation, but also have a significant contribution to the broadband noise in the human voice. In this work, the laryngeal flow is modeled either as an incompressible pulsatile jet confined in a two-dimensional channel, or a pressure-driven flow modulated by a pair of viscoelastic vocal folds through the flow--structure interaction. The flow in the supraglottal region is found to be dominated by large-scale vortices whose unsteady motions significantly deflect the glottal jet. In the flow--structure interaction, a hybrid model based on the immersed-boundary method is developed to simulate the flow-induced vocal fold vibration, which involves a three-dimensional vocal fold prototype and a two-dimensional viscous flow. Both the flow behavior and the vibratory characteristics of the vocal folds will be presented.

Comparative Tectonics of Europa and Ganymede

NASA Astrophysics Data System (ADS)

Pappalardo, R. T.; Collins, G. C.; Prockter, L. M.; Head, J. W.

2000-10-01

Europa and Ganymede are sibling satellites with tectonic similarities and differences. Ganymede's ancient dark terrain is crossed by furrows, probably related to ancient large impacts, and has been normal faulted to various degrees. Bright grooved is pervasively deformed at multiple scales and is locally highly strained, consistent with normal faulting of an ice-rich lithosphere above a ductile asthenosphere, along with minor horizontal shear. Little evidence has been identified for compressional structures. The relative roles of tectonism and icy cryovolcanism in creating bright grooved terrain is an outstanding issue. Some ridge and trough structures within Europa's bands show tectonic similarities to Ganymede's grooved terrain, specifically sawtooth structures resembling normal fault blocks. Small-scale troughs are consistent with widened tension fractures. Shearing has produced transtensional and transpressional structures in Europan bands. Large-scale folds are recognized on Europa, with synclinal small-scale ridges and scarps probably representing folds and/or thrust blocks. Europa's ubiquitous double ridges may have originated as warm ice upwelled along tidally heated fracture zones. The morphological variety of ridges and troughs on Europa imply that care must be taken in inferring their origin. The relative youth of Europa's surface means that the satellite has preserved near-pristine morphologies of many structures, though sputter erosion could have altered the morphology of older topography. Moderate-resolution imaging has revealed lesser apparent diversity in Ganymede's ridge and trough types. Galileo's 28th orbit has brought new 20 m/pixel imaging of Ganymede, allowing direct comparison to Europa's small-scale structures.

Large-scale splay faults on a strike-slip fault system: The Yakima Folds, Washington State

USGS Publications Warehouse

Pratt, Thomas L.

2012-01-01

The Yakima Folds (YF) comprise anticlines above reverse faults cutting flows of the Miocene Columbia River Basalt Group of central Washington State. The YF are bisected by the ~1100-km-long Olympic-Wallowa Lineament (OWL), which is an alignment of topographic features including known faults. There is considerable debate about the origin and earthquake potential of both the YF and OWL, which lie near six major dams and a large nuclear waste storage site. Here I show that the trends of the faults forming the YF relative to the OWL match remarkably well the trends of the principal stress directions at the end of a vertical strike-slip fault. This comparison and the termination of some YF against the OWL are consistent with the YF initially forming as splay faults caused by an along-strike decrease in the amount of strike-slip on the OWL. The hypothesis is that the YF faults initially developed as splay faults in the early to mid Miocene under NNW-oriented principal compressive stress, but the anticlines subsequently grew with thrust motion after the principal compressive stress direction rotated to N-S or NNE after the mid-Miocene. A seismic profile across one of the YF anticlines shows folding at about 7 km depth, indicating deformation of sub-basalt strata. The seismic profile and the hypothesized relationship between the YF and the OWL suggest that the structures are connected in the middle or lower crust, and that the faults forming the YF are large-scale splay faults associated with a major strike-slip fault system.

Spatial organization of chromatin domains and compartments in single chromosomes

NASA Astrophysics Data System (ADS)

Wang, Siyuan; Su, Jun-Han; Beliveau, Brian; Bintu, Bogdan; Moffitt, Jeffrey; Wu, Chao-Ting; Zhuang, Xiaowei

The spatial organization of chromatin critically affects genome function. Recent chromosome-conformation-capture studies have revealed topologically associating domains (TADs) as a conserved feature of chromatin organization, but how TADs are spatially organized in individual chromosomes remains unknown. Here, we developed an imaging method for mapping the spatial positions of numerous genomic regions along individual chromosomes and traced the positions of TADs in human interphase autosomes and X chromosomes. We observed that chromosome folding deviates from the ideal fractal-globule model at large length scales and that TADs are largely organized into two compartments spatially arranged in a polarized manner in individual chromosomes. Active and inactive X chromosomes adopt different folding and compartmentalization configurations. These results suggest that the spatial organization of chromatin domains can change in response to regulation.

NoFold: RNA structure clustering without folding or alignment.

PubMed

Middleton, Sarah A; Kim, Junhyong

2014-11-01

Structures that recur across multiple different transcripts, called structure motifs, often perform a similar function-for example, recruiting a specific RNA-binding protein that then regulates translation, splicing, or subcellular localization. Identifying common motifs between coregulated transcripts may therefore yield significant insight into their binding partners and mechanism of regulation. However, as most methods for clustering structures are based on folding individual sequences or doing many pairwise alignments, this results in a tradeoff between speed and accuracy that can be problematic for large-scale data sets. Here we describe a novel method for comparing and characterizing RNA secondary structures that does not require folding or pairwise alignment of the input sequences. Our method uses the idea of constructing a distance function between two objects by their respective distances to a collection of empirical examples or models, which in our case consists of 1973 Rfam family covariance models. Using this as a basis for measuring structural similarity, we developed a clustering pipeline called NoFold to automatically identify and annotate structure motifs within large sequence data sets. We demonstrate that NoFold can simultaneously identify multiple structure motifs with an average sensitivity of 0.80 and precision of 0.98 and generally exceeds the performance of existing methods. We also perform a cross-validation analysis of the entire set of Rfam families, achieving an average sensitivity of 0.57. We apply NoFold to identify motifs enriched in dendritically localized transcripts and report 213 enriched motifs, including both known and novel structures. © 2014 Middleton and Kim; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

The cutting of metals via plastic buckling

PubMed Central

Viswanathan, Koushik; Ho, Yeung; Chandrasekar, Srinivasan

2017-01-01

The cutting of metals has long been described as occurring by laminar plastic flow. Here we show that for metals with large strain-hardening capacity, laminar flow mode is unstable and cutting instead occurs by plastic buckling of a thin surface layer. High speed in situ imaging confirms that the buckling results in a small bump on the surface which then evolves into a fold of large amplitude by rotation and stretching. The repeated occurrence of buckling and folding manifests itself at the mesoscopic scale as a new flow mode with significant vortex-like components—sinuous flow. The buckling model is validated by phenomenological observations of flow at the continuum level and microstructural characteristics of grain deformation and measurements of the folding. In addition to predicting the conditions for surface buckling, the model suggests various geometric flow control strategies that can be effectively implemented to promote laminar flow, and suppress sinuous flow in cutting, with implications for industrial manufacturing processes. The observations impinge on the foundations of metal cutting by pointing to the key role of stability of laminar flow in determining the mechanism of material removal, and the need to re-examine long-held notions of large strain deformation at surfaces. PMID:28690406

The cutting of metals via plastic buckling.

PubMed

Udupa, Anirudh; Viswanathan, Koushik; Ho, Yeung; Chandrasekar, Srinivasan

2017-06-01

The cutting of metals has long been described as occurring by laminar plastic flow. Here we show that for metals with large strain-hardening capacity, laminar flow mode is unstable and cutting instead occurs by plastic buckling of a thin surface layer. High speed in situ imaging confirms that the buckling results in a small bump on the surface which then evolves into a fold of large amplitude by rotation and stretching. The repeated occurrence of buckling and folding manifests itself at the mesoscopic scale as a new flow mode with significant vortex-like components-sinuous flow. The buckling model is validated by phenomenological observations of flow at the continuum level and microstructural characteristics of grain deformation and measurements of the folding. In addition to predicting the conditions for surface buckling, the model suggests various geometric flow control strategies that can be effectively implemented to promote laminar flow, and suppress sinuous flow in cutting, with implications for industrial manufacturing processes. The observations impinge on the foundations of metal cutting by pointing to the key role of stability of laminar flow in determining the mechanism of material removal, and the need to re-examine long-held notions of large strain deformation at surfaces.

The cutting of metals via plastic buckling

NASA Astrophysics Data System (ADS)

Udupa, Anirudh; Viswanathan, Koushik; Ho, Yeung; Chandrasekar, Srinivasan

2017-06-01

The cutting of metals has long been described as occurring by laminar plastic flow. Here we show that for metals with large strain-hardening capacity, laminar flow mode is unstable and cutting instead occurs by plastic buckling of a thin surface layer. High speed in situ imaging confirms that the buckling results in a small bump on the surface which then evolves into a fold of large amplitude by rotation and stretching. The repeated occurrence of buckling and folding manifests itself at the mesoscopic scale as a new flow mode with significant vortex-like components-sinuous flow. The buckling model is validated by phenomenological observations of flow at the continuum level and microstructural characteristics of grain deformation and measurements of the folding. In addition to predicting the conditions for surface buckling, the model suggests various geometric flow control strategies that can be effectively implemented to promote laminar flow, and suppress sinuous flow in cutting, with implications for industrial manufacturing processes. The observations impinge on the foundations of metal cutting by pointing to the key role of stability of laminar flow in determining the mechanism of material removal, and the need to re-examine long-held notions of large strain deformation at surfaces.

Disproportionate photosynthetic decline and inverse relationship between constitutive and induced volatile emissions upon feeding of Quercus robur leaves by large larvae of gypsy moth (Lymantria dispar)

PubMed Central

Copolovici, Lucian; Pag, Andreea; Kännaste, Astrid; Bodescu, Adina; Tomescu, Daniel; Copolovici, Dana; Soran, Maria-Loredana; Niinemets, Ülo

2018-01-01

Gypsy moth (Lymantria dispar L., Lymantriinae) is a major pest of pedunculate oak (Quercus robur) forests in Europe, but how its infections scale with foliage physiological characteristics, in particular with photosynthesis rates and emissions of volatile organic compounds has not been studied. Differently from the majority of insect herbivores, large larvae of L. dispar rapidly consume leaf area, and can also bite through tough tissues, including secondary and primary leaf veins. Given the rapid and devastating feeding responses, we hypothesized that infection of Q. robur leaves by L. dispar leads to disproportionate scaling of leaf photosynthesis and constitutive isoprene emissions with damaged leaf area, and to less prominent enhancements of induced volatile release. Leaves with 0% (control) to 50% of leaf area removed by larvae were studied. Across this range of infection severity, all physiological characteristics were quantitatively correlated with the degree of damage, but all these traits changed disproportionately with the degree of damage. The net assimilation rate was reduced by almost 10-fold and constitutive isoprene emissions by more than 7-fold, whereas the emissions of green leaf volatiles, monoterpenes, methyl salicylate and the homoterpene (3E)-4,8-dimethy-1,3,7-nonatriene scaled negatively and almost linearly with net assimilation rate through damage treatments. This study demonstrates that feeding by large insect herbivores disproportionately alters photosynthetic rate and constitutive isoprene emissions. Furthermore, the leaves have a surprisingly large capacity for enhancement of induced emissions even when foliage photosynthetic function is severely impaired. PMID:29367792

Topography of funneled landscapes determines the thermodynamics and kinetics of protein folding

PubMed Central

Wang, Jin; Oliveira, Ronaldo J.; Chu, Xiakun; Whitford, Paul C.; Chahine, Jorge; Han, Wei; Wang, Erkang; Onuchic, José N.; Leite, Vitor B.P.

2012-01-01

The energy landscape approach has played a fundamental role in advancing our understanding of protein folding. Here, we quantify protein folding energy landscapes by exploring the underlying density of states. We identify three quantities essential for characterizing landscape topography: the stabilizing energy gap between the native and nonnative ensembles δE, the energetic roughness ΔE, and the scale of landscape measured by the entropy S. We show that the dimensionless ratio between the gap, roughness, and entropy of the system accurately predicts the thermodynamics, as well as the kinetics of folding. Large Λ implies that the energy gap (or landscape slope towards the native state) is dominant, leading to more funneled landscapes. We investigate the role of topological and energetic roughness for proteins of different sizes and for proteins of the same size, but with different structural topologies. The landscape topography ratio Λ is shown to be monotonically correlated with the thermodynamic stability against trapping, as characterized by the ratio of folding temperature versus trapping temperature. Furthermore, Λ also monotonically correlates with the folding kinetic rates. These results provide the quantitative bridge between the landscape topography and experimental folding measurements. PMID:23019359

Paleomagnetic and Anisotropy of Magnetic Susceptibility (AMS) Documentation of the Formation of Large-Scale Rheomorphic Structures in the 2.06 Ma Huckleberry Ridge Tuff, Eastern Idaho

NASA Astrophysics Data System (ADS)

Geissman, J. W.; Holm, D.; Harlan, S. S.

2006-12-01

In the Teton River Valley, east of Rexburg, Idaho, the ca. 2.06 Ma Huckleberry Ridge Tuff is about 130 m thick, exceedingly well-exposed, and displays large-scale (100-150 m+ amplitude) rheomorphic folds, with eutaxitic fabrics that are parallel to inferred primary internal zonation (e.g. boundary between basal vitrophyre and overlying devitrified part of the pyroclastic deposit) as well as the basal contact with older deposits defining the fold geometries. One 150 m amplitude fold , is well-exposed on the north side of the valley about 2.5 km east of Teton Dam, has a NW trending fold axis and has a southwest limb that is overturned by about 45o. Samples were collected from 16 sites in this fold, on both limbs and the hinge area, to test the hypothesis that folding took place above maximum TRM blocking temperatures (about 580C). Progressive AF and thermal demagnetization both yield characteristic magnetizations of southwest to south-southwest declination and shallow inclination removed over a range of peak fields (typically between 20 and 80 mT) and laboratory unblocking temperatures (typically between 350 and 580C). The preliminary determination of an in situ mean based on the 16 sites is about D = 215°, I = -5°, a95= 5°, N = 16 site means). The direction of this ChRM is statistically indistinguishable from that reported by previous studies of the tuff (e.g. Reynolds, 1977, JGR; Byrd et al., 1994, JGR). The trend of the fold axis is orthogonal to this declination; the paleomagnetic fold test applied to these data is negative, with k values continuously decreasing upon unfolding, thus indicating that the entire structure in the tuff formed after the well-developed compaction fabric was acquired, at a temperature above maximum blocking temperatures of the ChRM. Post-compaction, high temperature deformation is consistent with field evidence indicating plastic secondary deformation of much of the tuff prior to devitrification. Rapid strain rates probably contributed to the formation of brittle features in the uppermost parts of the tuff (joints and fissures). AMS fabrics, at the site level, are typically very well-defined, with AMS foliations roughly parallel to compaction fabric, with K1 (maximum principal susceptibility) axes typically directed in a southwest-northeast orientation.

Folded Supersymmetry and the LDP Paradox

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

Burdman, Gustavo; Chacko, Z.; Goh, Hock-Seng

2006-09-21

We present a new class of models that stabilize the weak scale against radiative corrections up to scales of order 5 TeV without large corrections to precision electroweak observables. In these ''folded supersymmetric'' theories the one loop quadratic divergences of the Standard Model Higgs field are canceled by opposite spin partners, but the gauge quantum numbers of these new particles are in general different from those of the conventional superpartners. This class of models is built around the correspondence that exists in the large N limit between the correlation functions of supersymmetric theories and those of their non-supersymmetric orbifold daughters.more » By identifying the mechanism which underlies the cancellation of one loop quadratic divergences in these theories, we are able to construct simple extensions of the Standard Model which are radiatively stable at one loop. Ultraviolet completions of these theories can be obtained by imposing suitable boundary conditions on an appropriate supersymmetric higher dimensional theory compactified down to four dimensions. We construct a specific model based on these ideas which stabilizes the weak scale up to about 20 TeV and where the states which cancel the top loop are scalars not charged under Standard Model color. Its collider signatures are distinct from conventional supersymmetric theories and include characteristic events with hard leptons and missing energy.« less

The Qartaba Anticline (central Mount Lebanon): Implications for the tectonic evolution of onshore Lebanon

NASA Astrophysics Data System (ADS)

Asmar, Chloe; Grasemann, Bernhard; Nader, Fadi; Tari, Gabor

2013-04-01

The area of Lebanon includes three major physiographic elements (Mount Lebanon, the Anti-Lebanon mountain chain, and the Bekaa Valley in between). The western Lebanese ranges (Mount Lebanon) stretch along the coast of the Mediterranean Sea. The prominent Qartaba Anticline is located on the western side of the northern Mount Lebanon. The studied part of this anticline (~20 km long, ~5 km wide) represents a large-scale box-fold structure bounded by two SW- and NE-vergent monoclines. The mechanism and timing of folding of the Qartaba Anticline are still debated and are not well understood. During several field visits hundreds of structural measurements were made in the study area in order to better constrain the three-dimensional shape of the Qartaba structure. The data show that the eastern and western flanks of the anticline represent oppositely verging monoclines with average dip values increasing from around 15° at the outer limits of the structure to 30° towards the middle of the flanks and reaching values up to 90° at the uppermost flanks. The strata become more or less horizontal on the top of the structure, a few hundreds meters away from the limbs of the monoclines. Therefore the whole structure resembles a large scale box-fold. Although several generations of brittle faults cross cut the Qartaba structure, no large scale faults have been identified in the field, which could be interpreted as directly related to the folding process itself. Instead, the folding and the limb rotation are strongly associated with dissolution-precipitation deformation mechanisms showing multi-generations of axial plane stylolites at high angles to the bedding planes within the hinge zones of the flanking monoclines. Pronounced stratigraphic boundaries, such as the one between the Middle to Upper Jurassic Kesrouane and Bhannes Formations, have been taken as reference surfaces in previous reports in order to construct structural and isopach contour maps of the Qartaba structure. In this study, contours were digitized from available maps as well as stratigraphic and structural cross sections. Dip/strike measurements taken in the field combined with measurements derived from high-resolution satellite images were also utilized in the digitized maps. The new three dimensional structural model of the Qartaba Anticline contains important information about the subsurface geology and features susbtantial implications for the tectonic evolution of the broader area in Lebanon (part of eastern margin of the Levant Basin).

Predicting chromatin architecture from models of polymer physics.

PubMed

Bianco, Simona; Chiariello, Andrea M; Annunziatella, Carlo; Esposito, Andrea; Nicodemi, Mario

2017-03-01

We review the picture of chromatin large-scale 3D organization emerging from the analysis of Hi-C data and polymer modeling. In higher mammals, Hi-C contact maps reveal a complex higher-order organization, extending from the sub-Mb to chromosomal scales, hierarchically folded in a structure of domains-within-domains (metaTADs). The domain folding hierarchy is partially conserved throughout differentiation, and deeply correlated to epigenomic features. Rearrangements in the metaTAD topology relate to gene expression modifications: in particular, in neuronal differentiation models, topologically associated domains (TADs) tend to have coherent expression changes within architecturally conserved metaTAD niches. To identify the nature of architectural domains and their molecular determinants within a principled approach, we discuss models based on polymer physics. We show that basic concepts of interacting polymer physics explain chromatin spatial organization across chromosomal scales and cell types. The 3D structure of genomic loci can be derived with high accuracy and its molecular determinants identified by crossing information with epigenomic databases. In particular, we illustrate the case of the Sox9 locus, linked to human congenital disorders. The model in-silico predictions on the effects of genomic rearrangements are confirmed by available 5C data. That can help establishing new diagnostic tools for diseases linked to chromatin mis-folding, such as congenital disorders and cancer.

Accelerating electrostatic surface potential calculation with multi-scale approximation on graphics processing units.

PubMed

Anandakrishnan, Ramu; Scogland, Tom R W; Fenley, Andrew T; Gordon, John C; Feng, Wu-chun; Onufriev, Alexey V

2010-06-01

Tools that compute and visualize biomolecular electrostatic surface potential have been used extensively for studying biomolecular function. However, determining the surface potential for large biomolecules on a typical desktop computer can take days or longer using currently available tools and methods. Two commonly used techniques to speed-up these types of electrostatic computations are approximations based on multi-scale coarse-graining and parallelization across multiple processors. This paper demonstrates that for the computation of electrostatic surface potential, these two techniques can be combined to deliver significantly greater speed-up than either one separately, something that is in general not always possible. Specifically, the electrostatic potential computation, using an analytical linearized Poisson-Boltzmann (ALPB) method, is approximated using the hierarchical charge partitioning (HCP) multi-scale method, and parallelized on an ATI Radeon 4870 graphical processing unit (GPU). The implementation delivers a combined 934-fold speed-up for a 476,040 atom viral capsid, compared to an equivalent non-parallel implementation on an Intel E6550 CPU without the approximation. This speed-up is significantly greater than the 42-fold speed-up for the HCP approximation alone or the 182-fold speed-up for the GPU alone. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Kinematic evolution of a regional-scale gravity-driven deepwater fold-and-thrust belt: The Lamu Basin case-history (East Africa)

NASA Astrophysics Data System (ADS)

Cruciani, F.; Barchi, M. R.; Koyi, H. A.; Porreca, M.

2017-08-01

The deepwater fold-and-thrust belts (DWFTBs) are geological structures recently explored thanks to advances in offshore seismic imaging by oil industry. In this study we present a kinematic analysis based on three balanced cross-sections of depth-converted, 2-D seismic profiles along the offshore Lamu Basin (East African passive margin). This margin is characterized by a regional-scale DWFTB (> 450 km long), which is the product of gravity-driven contraction on the shelf that exhibits complex structural styles and differing amount of shortening along strike. Net shortening is up to 48 km in the northern wider part of the fold-and-thrust belt (≈ 180 km), diminishing to < 15 km toward the south, where the belt is markedly narrower (≈ 50 km). The three balanced profiles show a shortening percentage around 20% (comparable with the maximum values documented in other gravity-driven DWFTBs), with a significant variability along dip: higher values are achieved in the outer (i.e. down-dip) portion of the system, dominated by basinward-verging, imbricate thrust sheets. Fold wavelength increases landward, where doubly-verging structures and symmetric detachment folds accommodate a lower amount of shortening. Similar to other cases, a linear and systematic relationship between sedimentary thickness and fold wavelength is observed. Reconstruction of the rate of shortening through time within a fold-and-thrust belt shows that after an early phase of slow activation (Late Cretaceous), > 95% of net shortening was produced in < 10 Myr (during Paleocene). During this acme phase, which followed a period of high sedimentation rate, thrusts were largely synchronous and the shortening rate reached a maximum value of 5 mm/yr. The kinematic evolution reconstructed in this study suggests that the structural evolution of gravity-driven fold-and-thrust belts differs from the accretionary wedges and the collisional fold-and-thrust belts, where thrusts propagate in-sequence and shortening is uniformly accommodated along dip.

Fast-dynamo action in unsteady flows and maps in three dimensions

NASA Technical Reports Server (NTRS)

Bayly, B. J.; Childress, S.

1987-01-01

Unsteady fast-dynamo action is obtained in a family of stretch-fold-shear maps applied to a spatially periodic magnetic field in three dimensions. Exponential growth of a mean field in the limit of vanishing diffusivity is demonstrated by a numerical method which alternates instantaneous deformations with molecular diffusion over a finite time interval. Analysis indicates that the dynamo is a coherent feature of the large scales, essentially independent of the cascade of structure to small scales.

Global deformation on the surface of Venus

NASA Technical Reports Server (NTRS)

Bilotti, Frank; Connors, Chris; Suppe, John

1992-01-01

Large-scale mapping of tectonic structures on Venus shows that there is an organized global distribution to deformation. The structures we emphasize are linear compressive mountain belts, extensional rafted zones, and the small-scale but widely distributed wrinkle ridges. Ninety percent of the area of the planet's compressive mountain belts are concentrated in the northern hemisphere whereas the southern hemisphere is dominated by extension and small-scale compression. We propose that this striking concentration of fold belts in the northern hemisphere, along with the globe-encircling equatorial rift system, represents a global organization to deformation on Venus.

Molecular Precision at Micrometer Length Scales: Hierarchical Assembly of DNA-Protein Nanostructures.

PubMed

Schiffels, Daniel; Szalai, Veronika A; Liddle, J Alexander

2017-07-25

Robust self-assembly across length scales is a ubiquitous feature of biological systems but remains challenging for synthetic structures. Taking a cue from biology-where disparate molecules work together to produce large, functional assemblies-we demonstrate how to engineer microscale structures with nanoscale features: Our self-assembly approach begins by using DNA polymerase to controllably create double-stranded DNA (dsDNA) sections on a single-stranded template. The single-stranded DNA (ssDNA) sections are then folded into a mechanically flexible skeleton by the origami method. This process simultaneously shapes the structure at the nanoscale and directs the large-scale geometry. The DNA skeleton guides the assembly of RecA protein filaments, which provides rigidity at the micrometer scale. We use our modular design strategy to assemble tetrahedral, rectangular, and linear shapes of defined dimensions. This method enables the robust construction of complex assemblies, greatly extending the range of DNA-based self-assembly methods.

Dynamics of one-state downhill protein folding.

PubMed

Li, Peng; Oliva, Fabiana Y; Naganathan, Athi N; Muñoz, Victor

2009-01-06

The small helical protein BBL has been shown to fold and unfold in the absence of a free energy barrier according to a battery of quantitative criteria in equilibrium experiments, including probe-dependent equilibrium unfolding, complex coupling between denaturing agents, characteristic DSC thermogram, gradual melting of secondary structure, and heterogeneous atom-by-atom unfolding behaviors spanning the entire unfolding process. Here, we present the results of nanosecond T-jump experiments probing backbone structure by IR and end-to-end distance by FRET. The folding dynamics observed with these two probes are both exponential with common relaxation times but have large differences in amplitude following their probe-dependent equilibrium unfolding. The quantitative analysis of amplitude and relaxation time data for both probes shows that BBL folding dynamics are fully consistent with the one-state folding scenario and incompatible with alternative models involving one or several barrier crossing events. At 333 K, the relaxation time for BBL is 1.3 micros, in agreement with previous folding speed limit estimates. However, late folding events at room temperature are an order of magnitude slower (20 micros), indicating a relatively rough underlying energy landscape. Our results in BBL expose the dynamic features of one-state folding and chart the intrinsic time-scales for conformational motions along the folding process. Interestingly, the simple self-averaging folding dynamics of BBL are the exact dynamic properties required in molecular rheostats, thus supporting a biological role for one-state folding.

Cross-axis synchronous flow-through coil planet centrifuge for large-scale preparative counter-current chromatography. III. Performance of large-bore coils in slow planetary motion.

PubMed

Ito, Y; Zhang, T Y

1988-11-25

A preparative capability of the present cross-axis synchronous flow-through coil planet centrifuge was demonstrated with 0.5 cm I.D. multilayer coils. Results of the model studies with short coils indicated that the optimal separations are obtained at low revolutional speeds of 100-200 rpm in both central and lateral coil positions. Preparative separations were successfully performed on 2.5-10 g quantities of test samples in a pair of multilayer coils connected in series with a total capacity of 2.5 l. The sample loading capacity will be scaled up in several folds by increasing the column width.

The large scale structures of the Late Permian Zechstein 3 intra-salt stringer, northern Netherlands

NASA Astrophysics Data System (ADS)

van Gent, H.; Strozyk, F.; Urai, J. L.; de Keijzer, M.; Kukla, P. A.

2012-04-01

The three dimensional study of the internal structure of salt structures on the several different scales is of fundamental importance to understand mechanisms of salt tectonics, for intra-salt storage cavern stability, and for drilling in salt-prone petroleum systems with associated problems like borehole instability and overpressured fluids. While most salt-related studies depict salt as structureless bodies, detailed field-, well- and mining gallery mapping have shown an amazing spectrum of brittle, complexly folded, faulted and boudinaged intra-salt layers ("stringers"), but mostly on a very local scale. First detailed insights into these three-dimensionally heterogeneous and very complex structures of the layered evaporites were provided by observations in modern high-resolution 3D seismic data, such as across the Late Permian Zechstein in the Southern Permian Basin (SPB). In the northern Dutch onshore part of the SPB, the Z2 and Z3 halite interface is characterized by the seismically visible reflections of the 30-150 m thick Z3 anhydrite-carbonate layer that clearly resolves the complex intra-salt structure. This stringer shows a high fragmentation into blocks of several tens of meters to kilometres diameter with complexly folded and faulted structures that correlate to the regionally varying deformation stages of the Zechstein, as it is implied by the shape of Top Salt. After an extensive seismic mapping over the entire northern Netherlands, structures observed include an extensive network of thicker zones, inferred to result from early karstification. Later, this template of relatively strong zones was deformed into large scale folds and boudins as the result of salt tectonics. Non-plane-strain salt flow produced complex fold and boudin geometries that overprint each other. There are some indications of a feedback between the early internal evolution of this salt giant and the position of later salt structures. The stringer has a higher density then the surrounding halite, and in the literature there is some controversy concerning the sinking rates of single stringer fragments. We observed no structures indicative of sinking, but conclude that the present-day position of the blocks can be explained by internal folding of the entire salt section. In the end, this study aims at (i) improving the understanding of the development and dynamics of Zechstein halokinesis, (ii) gaining new insights into the 3D internal deformation in salt, and (iii) a linkage of processes in the layered evaporites with the deformation of the enclosing sub- and supra-salt sediments.

Nanoscale Dewetting Transition in Protein Complex Folding

PubMed Central

Hua, Lan; Huang, Xuhui; Liu, Pu; Zhou, Ruhong; Berne, Bruce J.

2011-01-01

In a previous study, a surprising drying transition was observed to take place inside the nanoscale hydrophobic channel in the tetramer of the protein melittin. The goal of this paper is to determine if there are other protein complexes capable of displaying a dewetting transition during their final stage of folding. We searched the entire protein data bank (PDB) for all possible candidates, including protein tetramers, dimers, and two-domain proteins, and then performed the molecular dynamics (MD) simulations on the top candidates identified by a simple hydrophobic scoring function based on aligned hydrophobic surface areas. Our large scale MD simulations found several more proteins, including three tetramers, six dimers, and two two-domain proteins, which display a nanoscale dewetting transition in their final stage of folding. Even though the scoring function alone is not sufficient (i.e., a high score is necessary but not sufficient) in identifying the dewetting candidates, it does provide useful insights into the features of complex interfaces needed for dewetting. All top candidates have two features in common: (1) large aligned (matched) hydrophobic areas between two corresponding surfaces, and (2) large connected hydrophobic areas on the same surface. We have also studied the effect on dewetting of different water models and different treatments of the long-range electrostatic interactions (cutoff vs PME), and found the dewetting phenomena is fairly robust. This work presents a few proteins other than melittin tetramer for further experimental studies of the role of dewetting in the end stages of protein folding. PMID:17608515

Spaceborne imaging radar - Geologic and oceanographic applications

NASA Technical Reports Server (NTRS)

Elachi, C.

1980-01-01

Synoptic, large-area radar images of the earth's land and ocean surface, obtained from the Seasat orbiting spacecraft, show the potential for geologic mapping and for monitoring of ocean surface patterns. Structural and topographic features such as lineaments, anticlines, folds and domes, drainage patterns, stratification, and roughness units can be mapped. Ocean surface waves, internal waves, current boundaries, and large-scale eddies have been observed in numerous images taken by the Seasat imaging radar. This article gives an illustrated overview of these applications.

Folded fabric tunes rock deformation and failure mode in the upper crust.

PubMed

Agliardi, F; Dobbs, M R; Zanchetta, S; Vinciguerra, S

2017-11-10

The micro-mechanisms of brittle failure affect the bulk mechanical behaviour and permeability of crustal rocks. In low-porosity crystalline rocks, these mechanisms are related to mineralogy and fabric anisotropy, while confining pressure, temperature and strain rates regulate the transition from brittle to ductile behaviour. However, the effects of folded anisotropic fabrics, widespread in orogenic settings, on the mechanical behaviour of crustal rocks are largely unknown. Here we explore the deformation and failure behaviour of a representative folded gneiss, by combining the results of triaxial deformation experiments carried out while monitoring microseismicity with microstructural and damage proxies analyses. We show that folded crystalline rocks in upper crustal conditions exhibit dramatic strength heterogeneity and contrasting failure modes at identical confining pressure and room temperature, depending on the geometrical relationships between stress and two different anisotropies associated to the folded rock fabric. These anisotropies modulate the competition among quartz- and mica-dominated microscopic damage processes, resulting in transitional brittle to semi-brittle modes under P and T much lower than expected. This has significant implications on scales relevant to seismicity, energy resources, engineering applications and geohazards.

Superior Red Blood Cell Generation from Human Pluripotent Stem Cells Through a Novel Microcarrier-Based Embryoid Body Platform.

PubMed

Sivalingam, Jaichandran; Lam, Alan Tin-Lun; Chen, Hong Yu; Yang, Bin Xia; Chen, Allen Kuan-Liang; Reuveny, Shaul; Loh, Yuin-Han; Oh, Steve Kah-Weng

2016-08-01

In vitro generation of red blood cells (RBCs) from human embryonic stem cells and human induced pluripotent stem cells appears to be a promising alternate approach to circumvent shortages in donor-derived blood supplies for clinical applications. Conventional methods for hematopoietic differentiation of human pluripotent stem cells (hPSC) rely on embryoid body (EB) formation and/or coculture with xenogeneic cell lines. However, most current methods for hPSC expansion and EB formation are not amenable for scale-up to levels required for large-scale RBC generation. Moreover, differentiation methods that rely on xenogenic cell lines would face obstacles for future clinical translation. In this study, we report the development of a serum-free and chemically defined microcarrier-based suspension culture platform for scalable hPSC expansion and EB formation. Improved survival and better quality EBs generated with the microcarrier-based method resulted in significantly improved mesoderm induction and, when combined with hematopoietic differentiation, resulted in at least a 6-fold improvement in hematopoietic precursor expansion, potentially culminating in a 80-fold improvement in the yield of RBC generation compared to a conventional EB-based differentiation method. In addition, we report efficient terminal maturation and generation of mature enucleated RBCs using a coculture system that comprised primary human mesenchymal stromal cells. The microcarrier-based platform could prove to be an appealing strategy for future scale-up of hPSC culture, EB generation, and large-scale generation of RBCs under defined and xeno-free conditions.

A computer program for the simulation of folds of different sizes under the influence of gravity

NASA Astrophysics Data System (ADS)

Vacas Peña, José M.; Martínez Catalán, José R.

2004-02-01

Folding&g is a computer program, based on the finite element method, developed to simulate the process of natural folding from small to large scales in two dimensions. Written in Pascal code and compiled with Borland Delphi 3.0, the program has a friendly interactive user interface and can be used for research as well as educational purposes. Four main menu options allow the user to import or to build and to save a model data file, select the type of graphic output, introduce and modify several physical parameters and enter the calculation routines. The program employs isoparametric, initially rectangular elements with eight nodes, which can sustain large deformations. The mathematical procedure is based on the elasticity equations, but has been modified to simulate a viscous rheology, either linear or of power-law type. The parameters to be introduced include either the linear viscosity, or, when the viscosity is non-linear, the material constant, activation energy, temperature and power of the differential stress. All the parameters can be set by rows, which simulate layers. A toggle permits gravity to be introduced into the calculations. In this case, the density of the different rows must be specified, and the sizes of the finite elements and of the whole model become meaningful. Viscosity values can also be assigned to blocks of several rows and columns, which permits the modelling of heterogeneities such as rectangular areas of high strength, which can be used to simulate shearing components interfering with the buckling process. The program is applied to several cases of folding, including a single competent bed and multilayers, and its results compared with analytical and experimental results. The influence of gravity is illustrated by the modelling of diapiric structures and of a large recumbent fold.

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

Kojima, S.; Yokosawa, M.; Matsuyama, M.

To study the practical application of a tritium separation process using Self-Developing Gas Chromatography (SDGC) using a Pd-Pt alloy, intermediate scale-up experiments (22 mm ID x 2 m length column) and the development of a computational simulation method have been conducted. In addition, intermediate scale production of Pd-Pt powder has been developed for the scale-up experiments.The following results were obtained: (1) a 50-fold scale-up from 3 mm to 22 mm causes no significant impact on the SDGC process; (2) the Pd-Pt alloy powder is applicable to a large size SDGC process; and (3) the simulation enables preparation of a conceptualmore » design of a SDGC process for tritium separation.« less

Highly Efficient Large-Scale Lentiviral Vector Concentration by Tandem Tangential Flow Filtration

PubMed Central

Cooper, Aaron R.; Patel, Sanjeet; Senadheera, Shantha; Plath, Kathrin; Kohn, Donald B.; Hollis, Roger P.

2014-01-01

Large-scale lentiviral vector (LV) concentration can be inefficient and time consuming, often involving multiple rounds of filtration and centrifugation. This report describes a simpler method using two tangential flow filtration (TFF) steps to concentrate liter-scale volumes of LV supernatant, achieving in excess of 2000-fold concentration in less than 3 hours with very high recovery (>97%). Large volumes of LV supernatant can be produced easily through the use of multi-layer flasks, each having 1720 cm2 surface area and producing ~560 mL of supernatant per flask. Combining the use of such flasks and TFF greatly simplifies large-scale production of LV. As a demonstration, the method is used to produce a very high titer LV (>1010 TU/mL) and transduce primary human CD34+ hematopoietic stem/progenitor cells at high final vector concentrations with no overt toxicity. A complex LV (STEMCCA) for induced pluripotent stem cell generation is also concentrated from low initial titer and used to transduce and reprogram primary human fibroblasts with no overt toxicity. Additionally, a generalized and simple multiplexed real- time PCR assay is described for lentiviral vector titer and copy number determination. PMID:21784103

Ground Deployment Demonstration and Material Testing for Solar Sail

NASA Astrophysics Data System (ADS)

Huang, Xiaoqi; Cheng, Zhengai; Liu, Yufei; Wang, Li

2016-07-01

Solar Sail is a kind of spacecraft that can achieve extremely high velocity by light pressure instead of chemical fuel. The great accelerate rely on its high area-to-mass ratio. So solar sail is always designed in huge size and it use ultra thin and light weight materials. For 100-meter class solar sail, two key points must be considered in the design process. They are fold-deployment method, and material property change in space environment. To test and verify the fold-deployment technology, a 8*8m principle prototype was developed. Sail membrane folding in method of IKAROS, Nanosail-D , and new proposed L-shape folding pattern were tested on this prototype. Their deployment properties were investigated in detail, and comparisons were made between them. Also, the space environment suitability of ultra thin polyimide films as candidate solar sail material was analyzed. The preliminary test results showed that membrane by all the folding method could deploy well. Moreover, sail membrane folding by L-shape pattern deployed more rapidly and more organized among the three folding pattern tested. The mechanical properties of the polyimide had no significant change after electron irradiation. As the preliminary research on the key technology of solar sail spacecraft, in this paper, the results of the study would provide important basis on large-scale solar sail membrane select and fold-deploying method design.

Boys, Girls and Communication: Their Views, Confidence and Why These Skills Matter

ERIC Educational Resources Information Center

Clark, Christina

2011-01-01

This is the first large-scale survey of young people's views on communication skills in the UK. The purpose of this survey was three-fold. Since a search of the published literature had highlighted real gaps in knowledge, the author and her colleagues wanted answers to the following questions: What do young people think about communication skills?…

High-efficiency Agrobacterium-mediated transformation of Norway spruce (Picea abies) and loblolly pine (Pinus taeda)

NASA Technical Reports Server (NTRS)

Wenck, A. R.; Quinn, M.; Whetten, R. W.; Pullman, G.; Sederoff, R.; Brown, C. S. (Principal Investigator)

1999-01-01

Agrobacterium-mediated gene transfer is the method of choice for many plant biotechnology laboratories; however, large-scale use of this organism in conifer transformation has been limited by difficult propagation of explant material, selection efficiencies and low transformation frequency. We have analyzed co-cultivation conditions and different disarmed strains of Agrobacterium to improve transformation. Additional copies of virulence genes were added to three common disarmed strains. These extra virulence genes included either a constitutively active virG or extra copies of virG and virB, both from pTiBo542. In experiments with Norway spruce, we increased transformation efficiencies 1000-fold from initial experiments where little or no transient expression was detected. Over 100 transformed lines expressing the marker gene beta-glucuronidase (GUS) were generated from rapidly dividing embryogenic suspension-cultured cells co-cultivated with Agrobacterium. GUS activity was used to monitor transient expression and to further test lines selected on kanamycin-containing medium. In loblolly pine, transient expression increased 10-fold utilizing modified Agrobacterium strains. Agrobacterium-mediated gene transfer is a useful technique for large-scale generation of transgenic Norway spruce and may prove useful for other conifer species.

Just enough inflation: power spectrum modifications at large scales

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

Cicoli, Michele; Downes, Sean; Dutta, Bhaskar

2014-12-01

We show that models of 'just enough' inflation, where the slow-roll evolution lasted only 50- 60 e-foldings, feature modifications of the CMB power spectrum at large angular scales. We perform a systematic analytic analysis in the limit of a sudden transition between any possible non-slow-roll background evolution and the final stage of slow-roll inflation. We find a high degree of universality since most common backgrounds like fast-roll evolution, matter or radiation-dominance give rise to a power loss at large angular scales and a peak together with an oscillatory behaviour at scales around the value of the Hubble parameter at themore » beginning of slow-roll inflation. Depending on the value of the equation of state parameter, different pre-inflationary epochs lead instead to an enhancement of power at low ℓ, and so seem disfavoured by recent observational hints for a lack of CMB power at ℓ∼< 40. We also comment on the importance of initial conditions and the possibility to have multiple pre-inflationary stages.« less

A viscoelastic strain energy principle expressed in fold thrust belts and other compressional regimes

NASA Astrophysics Data System (ADS)

Patton, Regan L.; Watkinson, A. John

2005-07-01

A mathematical folding theory for stratified viscoelastic media in layer parallel compression is presented. The second order fluid, in slow flow, is used to model rock rheological behavior because it is the simplest nonlinear constitutive equation exhibiting viscoelastic effects. Scaling and non-dimensionalization of the model system reveals the presence of Weissenberg number ( Wi), defined as a ratio of time scales τ*/( H*/ V*). V*/ H* is the strain rate (s -1) imposed by an assumed far field velocity V* acting on a layer of thickness H*, while τ* (s) is related to the relaxation of normal stresses. Our most significant finding is a transitional behavior as Wi→½, which is independent of the viscosity contrast. A change of variables shows that lengths associated with this transition are scaled by a parameter α=[(1-2 Wi)/(1+2 Wi)] 1/2, which is inversely proportional to local strain energy. On this basis a scaling law representing a distribution of non-dimensional wavelengths (wavelength/layer thickness) is derived. Geologically this is consistent with a transition from folding to faulting, as observed in fold-thrust belts. Folding, a distributed deformation scaling as Wi-1, is found to be energetically favored at non-dimensional wavelengths ranging from about three to seven. Furthermore, the transition from folding to faulting, a localized deformation scaling as ( αWi) -1, is predicted at a non-dimensional wavelength of about seven. These findings are consistent with measurements of thrust sheets in the Sawtooth Mountains of western Montana, USA and other fold-thrust belts. A review of the literature reveals a similar distribution of non-dimensional wavelengths spanning a wide range of observational scales in compressional deformation. Specific examples include lithospheric scale folding in the central Indian Basin and microscopic scale failure of ice columns between splay microcracks in laboratory studies.

Mola Topography Supports Drape-Folding Models for Polygonal Terrain of Utopia Planitia, Mars

NASA Technical Reports Server (NTRS)

McGill, George E.; Buczkowski, D. L.

2002-01-01

One of the most important questions we ask about Mars is whether or not there have ever been large bodies of standing water on the surface. The polygonal terrains of Utopia and Acidalia Planitiae are located in the lowest parts of the northern lowlands, the most logical places for water to pond and sediments to accumulate. Showing that polygonal terrain is sedimentary in origin would represent strong evidence in favor of a northern ocean. A number of hypotheses for the origin of the giant martian polygons have been proposed, from the cooling of lava to frost wedging to the desiccation of wet sediments, but Pechman showed that none of these familiar processes could be scaled up to martian dimensions. Two models for polygon origin attempt to explain the scale of the martian polygons by postulating drape folding of a cover material, either sedimentary or volcanic, over an uneven, buried surface. The drape folding would produce bending stresses in the surface layers that increase the probability of Fracturing over drape anticlines and suppress the probability of fracturing over drape synclines. However, both models require an additional source of extensional strain to produce the total strain needed to produce the observed troughs.

The Western Tauern Window (Eastern Alps): Timing and Interplay of Folds and Sinistral Shear Zones as Result of South-Alpine Indentation

NASA Astrophysics Data System (ADS)

Schneider, Susanne; Rosenberg, Claudio; Hammerschmidt, Konrad

2010-05-01

The Tauern Window (TW) is the only domain within the Eastern Alps where deep crustal, Tertiary metamorphic rocks were exhumed to surface. The window is bounded by large-scale faults, partly considered to be responsible for its exhumation (e.g., Selverstone 1988, Fügenschuh 1997), and it is also cross cut internally by large-scale shear zones, whose significance in terms of type and timing of deformation, exhumation, and large-scale kinematic links is the subject of our investigation. These shear zones (Ahorn, Olperer, Greiner, Ahrntal) are widespread throughout the western TW, from the mm- to the km-scale. They are sinistral and located in the steep limbs of upright antiforms, forming a mylonitic foliation, that strikes parallel to the axial planes of these upright folds. We present new structural and geochronological data, obtained by in-situ dating of microstructurally defined syn- and postkinematic grains, to constrain the duration and termination of folding and sinistral shearing. Previous dating suggested initiation of shearing contemporaneous to nappe stacking between 32-and 30Ma, ongoing until 15Ma (Glodny et al., 2008). However, the fabric of the dated grains was not related to deformation phases defined from structural overprinting relationships, and the classical separation technique did not allow to separate synkinematic from pre- and post- kinematic grains. The northern margin of the western TW is pervasively overprinted by the Ahorn Shear Zone (Rosenberg & Schneider 2008), which shows S-side up kinematic indicators in addition to the sinistral ones, and a pronounced southward increase in metamorphic grade from lower greenschist facies to amphibolite facies conditions, within 2km. Phengites of the mylonitic foliation dated with the Rb/Sr in-situ technique, yield formation ages of 14-24Ma . The southern margin of the western TW is overprinted by the sinistral Ahrntal Fault (Schneider et al. 2009), which cuts discordantly several nappes from the Zentralgneiss to the Upper Austroalpine units. Within the Upper Penninic nappes N-side up kinematic indicators occur, in addition to the sinistral ones. Newly formed biotites of Zentralgneiss rocks have been dated with the Rb/Sr technique (Kitzig et al. 2009), yielding 18-20Ma for their formation during sinistral deformation. Fine-grained phengites from the axial plane foliation of the upright folds were dated with the K/Ar method, yielding 14-17Ma. Ar/Ar in-situ LA analyses of sinistral mylonites (Ahorn, Olperer and Greiner) yield formation ages of syn-kinematic phengites between 24-12Ma. These grains are overgrown by post-kinematic phengites of 12-9Ma. Northeast of the western TW, sinistral shear is accommodated by the brittle sinistral SEMP Fault system, whose activity has been dated to 17Ma (Peresson & Decker 1997). Several sinistral shear zones (Ahorn, Greiner, Ahrntal) of the western TW may coalesce into the SEMP Fault (e.g., Linzer et al., 2002). In the west, the Ahorn Shear Zone terminates nearly 10km east of the Brenner Fault, into a NW-striking fold belt. The Ahrntal Fault continues into the Jaufen Fault, which merges with the brittle sinistral Giudicarie Fault. Motion along the Giudicarie Fault initiated in the Miocene (Stipp et al., 2004), or already in the Oligocene (Müller et al 2001). Based on these results, a temporal, kinematic and geometric continuity between sinistral shearing along the Giudicarie Fault, along the SEMP Fault, and throughout the western TW, can be assessed. The sinistral shear zones of the western TW are kinematically linked to upright folds, hence to crustal thickening. Upright folding and sinistral shearing were active since 24Ma and terminated at 12Ma. In summary, the sinistral displacements of the Giudicarie System appear to be partitioned into upright folds and sinistral, transpressive shear zones in the western Tauern Window, both of which contribute to its exhumation. The coalescence of the sinistral shear zones into the SEMP Fault System coincides with the eastern termination of the ENE-striking upright folds, possibly indicating transfer of shortening into a strike-slip displacement. Therefore, the western TW as a whole, represents a Miocene, sinistral transpressive belt, accommodating sinistral displacements associated with South-Alpine indentation by folding and sinistral shearing, and transferring these into sinistral movements associated with lateral escape along the SEMP System, until 12 Ma.

Kinetics of matching.

PubMed

Mark, T A; Gallistel, C R

1994-01-01

Rats responded on concurrent variable interval schedules of brain stimulation reward in 2-trial sessions. Between trials, there was a 16-fold reversal in the relative rate of reward. In successive, narrow time windows, the authors compared the ratio of the times spent on the 2 levers to the ratio of the rewards received. Time-allocation ratios tracked wide, random fluctuations in the reward ratio. The adjustment to the midsession reversal in relative rate of reward was largely completed within 1 interreward interval on the leaner schedule. Both results were unaffected by a 16-fold change in the combined rates of reward. The large, rapid, scale-invariant shifts in time-allocation ratios that underlie matching behavior imply that the subjective relative rate of reward can be determined by a very few of the most recent interreward intervals and that this estimate can directly determine the ratio of the expected stay durations.

k-neighborhood Decentralization: A Comprehensive Solution to Index the UMLS for Large Scale Knowledge Discovery

PubMed Central

Xiang, Yang; Lu, Kewei; James, Stephen L.; Borlawsky, Tara B.; Huang, Kun; Payne, Philip R.O.

2011-01-01

The Unified Medical Language System (UMLS) is the largest thesaurus in the biomedical informatics domain. Previous works have shown that knowledge constructs comprised of transitively-associated UMLS concepts are effective for discovering potentially novel biomedical hypotheses. However, the extremely large size of the UMLS becomes a major challenge for these applications. To address this problem, we designed a k-neighborhood Decentralization Labeling Scheme (kDLS) for the UMLS, and the corresponding method to effectively evaluate the kDLS indexing results. kDLS provides a comprehensive solution for indexing the UMLS for very efficient large scale knowledge discovery. We demonstrated that it is highly effective to use kDLS paths to prioritize disease-gene relations across the whole genome, with extremely high fold-enrichment values. To our knowledge, this is the first indexing scheme capable of supporting efficient large scale knowledge discovery on the UMLS as a whole. Our expectation is that kDLS will become a vital engine for retrieving information and generating hypotheses from the UMLS for future medical informatics applications. PMID:22154838

k-Neighborhood decentralization: a comprehensive solution to index the UMLS for large scale knowledge discovery.

PubMed

Xiang, Yang; Lu, Kewei; James, Stephen L; Borlawsky, Tara B; Huang, Kun; Payne, Philip R O

2012-04-01

The Unified Medical Language System (UMLS) is the largest thesaurus in the biomedical informatics domain. Previous works have shown that knowledge constructs comprised of transitively-associated UMLS concepts are effective for discovering potentially novel biomedical hypotheses. However, the extremely large size of the UMLS becomes a major challenge for these applications. To address this problem, we designed a k-neighborhood Decentralization Labeling Scheme (kDLS) for the UMLS, and the corresponding method to effectively evaluate the kDLS indexing results. kDLS provides a comprehensive solution for indexing the UMLS for very efficient large scale knowledge discovery. We demonstrated that it is highly effective to use kDLS paths to prioritize disease-gene relations across the whole genome, with extremely high fold-enrichment values. To our knowledge, this is the first indexing scheme capable of supporting efficient large scale knowledge discovery on the UMLS as a whole. Our expectation is that kDLS will become a vital engine for retrieving information and generating hypotheses from the UMLS for future medical informatics applications. Copyright © 2011 Elsevier Inc. All rights reserved.

HiQuant: Rapid Postquantification Analysis of Large-Scale MS-Generated Proteomics Data.

PubMed

Bryan, Kenneth; Jarboui, Mohamed-Ali; Raso, Cinzia; Bernal-Llinares, Manuel; McCann, Brendan; Rauch, Jens; Boldt, Karsten; Lynn, David J

2016-06-03

Recent advances in mass-spectrometry-based proteomics are now facilitating ambitious large-scale investigations of the spatial and temporal dynamics of the proteome; however, the increasing size and complexity of these data sets is overwhelming current downstream computational methods, specifically those that support the postquantification analysis pipeline. Here we present HiQuant, a novel application that enables the design and execution of a postquantification workflow, including common data-processing steps, such as assay normalization and grouping, and experimental replicate quality control and statistical analysis. HiQuant also enables the interpretation of results generated from large-scale data sets by supporting interactive heatmap analysis and also the direct export to Cytoscape and Gephi, two leading network analysis platforms. HiQuant may be run via a user-friendly graphical interface and also supports complete one-touch automation via a command-line mode. We evaluate HiQuant's performance by analyzing a large-scale, complex interactome mapping data set and demonstrate a 200-fold improvement in the execution time over current methods. We also demonstrate HiQuant's general utility by analyzing proteome-wide quantification data generated from both a large-scale public tyrosine kinase siRNA knock-down study and an in-house investigation into the temporal dynamics of the KSR1 and KSR2 interactomes. Download HiQuant, sample data sets, and supporting documentation at http://hiquant.primesdb.eu .

Large-scale impacts of herbivores on the structural diversity of African savannas

PubMed Central

Asner, Gregory P.; Levick, Shaun R.; Kennedy-Bowdoin, Ty; Knapp, David E.; Emerson, Ruth; Jacobson, James; Colgan, Matthew S.; Martin, Roberta E.

2009-01-01

African savannas are undergoing management intensification, and decision makers are increasingly challenged to balance the needs of large herbivore populations with the maintenance of vegetation and ecosystem diversity. Ensuring the sustainability of Africa's natural protected areas requires information on the efficacy of management decisions at large spatial scales, but often neither experimental treatments nor large-scale responses are available for analysis. Using a new airborne remote sensing system, we mapped the three-dimensional (3-D) structure of vegetation at a spatial resolution of 56 cm throughout 1640 ha of savanna after 6-, 22-, 35-, and 41-year exclusions of herbivores, as well as in unprotected areas, across Kruger National Park in South Africa. Areas in which herbivores were excluded over the short term (6 years) contained 38%–80% less bare ground compared with those that were exposed to mammalian herbivory. In the longer-term (> 22 years), the 3-D structure of woody vegetation differed significantly between protected and accessible landscapes, with up to 11-fold greater woody canopy cover in the areas without herbivores. Our maps revealed 2 scales of ecosystem response to herbivore consumption, one broadly mediated by geologic substrate and the other mediated by hillslope-scale variation in soil nutrient availability and moisture conditions. Our results are the first to quantitatively illustrate the extent to which herbivores can affect the 3-D structural diversity of vegetation across large savanna landscapes. PMID:19258457

Tectonic evolution of kid metamorphic complex and the recognition of Najd fault system in South East Sinai, Egypt

NASA Astrophysics Data System (ADS)

Sultan, Yasser M.; El-Shafei, Mohamed K.; Arnous, Mohamed O.

2017-03-01

A low-to medium-grade metamorphic belt of a volcano-sedimentary succession occurs in the eastern side of South Sinai as a part of the northernmost extension of the Arabian-Nubian Shield in Egypt. The belt is known as the Kid metamorphic complex. It is considered as one of the major belt among the other exposed metamorphic belts in South Sinai. Here, we detect and investigate the signature of the Najd Fault system in South Sinai based on detailed structural analysis in field and digital image processing. The enhanced satellite image and the geo-spatial distributions confirm that the Kid belt is essentially composed of nine Precambrian units. Field relations and geometrical analysis of the measured structural data revealed that the study area underwent four successive deformational phases (D1-D4). D1 is an upright tight to isoclinal large-scale folds that caused few F1 small-scale folds and a steeply dipping S1 axial plane foliation. The second deformational event D2 produced dominant of sub-horizontal S2 foliation planes accompanied with recumbent isoclinal folds and NW-SE trending L2 lineations. The main sense during D2 was top-to-the-NW with local reversals to the SE. The third folding generations F3 is recorded as axial plane S3-surfaces and is characterized by open concentric folding that overprinting both F1 and F2 folds and has a flexural-slip mechanism. F3 fold hinges plunge to the west-northwest or east-southeast indicate north-northeast-south-southwest shortening during D3. The fourth deformational event D4 is characterized by NE plunging open concentric folding overprint the pre-existing fold generations and formed under flexural slip mechanism reflecting coaxial deformation and indicating change in the stress regime as a result of the change in shortening from NE-SW to NW-SE. This phase is probably accompanied with the final assembly of east and west Gondwana. The dextral NW-SE shear zone that bounded the southwestern portion of the metamorphic belt is probably related to reactivation of the Najd fault system during Oligo-Miocene in South Sinai.

Large-scale deformational systems in the South Polar Layered Deposits (Promethei Lingula, Mars): "Soft-sediment" and Deep-Seated Gravitational Slope Deformations Mechanisms

NASA Astrophysics Data System (ADS)

Guallini, Luca; Brozzetti, Francesco; Marinangeli, Lucia

2012-08-01

The present study is the first attempt at a detailed structural and kinematic analysis of large-scale deformational systems observed in the South Polar Layered Deposits (SPLDs) in the Promethei Lingula (PL) margins (Mars). By systematically collecting attitude data referable to previously unknown deformational structures and defining the cross-cut relationships of the structures, we reconstructed a deformational history consisting of two superimposed, well-defined stages. The first stage is dominated by large-scale strike-slip and transtensional faults arranged into conjugate systems and delimiting shear zones that show a wide range of subsidiary structures, including normal and reverse faults, drag folds, boudins, S-C tectonites and sub-horizontal interstratal shear planes marked by sygmoidal boudins. Other typical structures referable to this event are ductile folds (locally true convolute folds) and lobes (ball-and-pillow structures) affecting certain marker beds of the succession. We suggest that the structural assemblage might be the expression of a shallow soft-sediment tectonics that possibly occurred during warm periods of the South Pole climate. The second stage seems to affect the weaker and in certain cases pre-deformed stratigraphic levels of the SPLD succession. This stage is mainly characterized by extensional deformations caused by gravity. The consequence of the deformations is the nucleation of Deep-Seated Gravitational Slope Deformations (DSGSDs) marked by typical morphostructures, such as scarps, trenches and bulging basal contractant zones. These phenomena were never observed within an ice cap. According to terrestrial modeling, these slow collapses were caused by (1) the presence of detachment levels (i.e., subhorizontal bedding planes) along which the ice-sheet margins can slide and (2) the development of listric faults within the glacial mass, which merge with sub-horizontal shear planes in the subsurface. The presence of complex deformational systems in the SPLD necessarily implies that a large-scale dynamics of the ice-sheet occurred in the past. The relatively fast internal creep and basal/internal sliding, inferable from the structure assemblage, can be due to partial melting of the ice possibly caused by climatic changes in the Promethei Lingula region. In this manner, we believe that climate heating (which, according to the literature, is likely caused by orbital variations) softened some of the SPLD layers, triggering or accelerating the ice sheet's outward movement. The evidence of a marked disharmonic deformational style through the SPLD succession suggests the possibility of local periodic compositional variations in the sequence.

Miocene−Pleistocene deformation of the Saddle Mountains: Implications for seismic hazard in central Washington, USA

USGS Publications Warehouse

Staisch, Lydia; Kelsey, Harvey; Sherrod, Brian; Möller, Andreas; Paces, James B.; Blakely, Richard J.; Styron, Richard

2017-01-01

The Yakima fold province, located in the backarc of the Cascadia subduction zone, is a region of active strain accumulation and deformation distributed across a series of fault-cored folds. The geodetic network in central Washington has been used to interpret large-scale N-S shortening and westward-increasing strain; however, geodetic data are unable to resolve shortening rates across individual structures in this low-strain-rate environment. Resolving fault geometries, slip rates, and timing of faulting in the Yakima fold province is critically important to seismic hazard assessment for nearby infrastructure and population centers.The Saddle Mountains anticline is one of the most prominent Yakima folds. It is unique within the Yakima fold province in that the syntectonic strata of the Ringold Formation are preserved and provide a record of deformation and drainage reorganization. Here, we present new stratigraphic columns, U-Pb zircon tephra ages, U-series caliche ages, and geophysical modeling that constrain two line-balanced and retrodeformed cross sections. These new constraints indicate that the Saddle Mountains anticline has accommodated 1.0−1.3 km of N-S shortening since 10 Ma, that shortening increases westward along the anticline, and that the average slip rate has increased 6-fold since 6.8 Ma. Provenance analysis suggests that the source terrane for the Ringold Formation was similar to that of the modern Snake River Plain. Using new slip rates and structural constraints, we calculate the strain accumulation time, interpretable as a recurrence interval, for earthquakes on the Saddle Mountains fault and find that large-magnitude earthquakes could rupture along the Saddle Mountains fault every 2−11 k.y.

Simulating Thin Sheets: Buckling, Wrinkling, Folding and Growth

NASA Astrophysics Data System (ADS)

Vetter, Roman; Stoop, Norbert; Wittel, Falk K.; Herrmann, Hans J.

2014-03-01

Numerical simulations of thin sheets undergoing large deformations are computationally challenging. Depending on the scenario, they may spontaneously buckle, wrinkle, fold, or crumple. Nature's thin tissues often experience significant anisotropic growth, which can act as the driving force for such instabilities. We use a recently developed finite element model to simulate the rich variety of nonlinear responses of Kirchhoff-Love sheets. The model uses subdivision surface shape functions in order to guarantee convergence of the method, and to allow a finite element description of anisotropically growing sheets in the classical Rayleigh-Ritz formalism. We illustrate the great potential in this approach by simulating the inflation of airbags, the buckling of a stretched cylinder, as well as the formation and scaling of wrinkles at free boundaries of growing sheets. Finally, we compare the folding of spatially confined sheets subject to growth and shrinking confinement to find that the two processes are equivalent.

Unravelling Origami Metamaterial Behavior

NASA Astrophysics Data System (ADS)

Eidini, Maryam; Paulino, Glaucio

2015-03-01

Origami has shown to be a substantial source of inspiration for innovative design of mechanical metamaterials for which the material properties arise from their geometry and structural layout. Most research on origami-inspired materials relies on known patterns, especially on classic Miura-ori pattern. In the present research, we have created origami-inspired metamaterials and we have shown that the folded materials possess properties as remarkable as those of Miura-ori on which there is a lot of recent research. We have also introduced and placed emphasis on several important concepts that are confused or overlooked in the literature, e.g. concept of planar Poisson's ratio for folded materials from different conceptual viewpoints, and we have clarified the importance of such concepts by applying them to the folded sheet metamaterials introduced in our research. The new patterns are appropriate for a broad range of applications, from mechanical metamaterials to deployable and kinetic structures, at both small and large scales.

The effects of light, primary production, and temperature on bacterial production at Station ALOHA

NASA Astrophysics Data System (ADS)

Viviani, D. A.; Church, M. J.

2016-02-01

In the open oceans, bacterial metabolism is responsible for a large fraction of the movement of reduced carbon through these ecosystems. While broad meta-analyses suggest that factors such as temperature or primary production control rates of bacterial production over large geographic scales, to date little is known about how these factors influence variability in bacterial production in the open sea. Here we present two years of measurements of 3H-leucine incorporation, a proxy for bacterial production, at the open ocean field site of the Hawaii Ocean Time-series, Station ALOHA (22° 45'N, 158° 00'W). By examining 3H-leucine incorporation over monthly, daily, and hourly scales, this work provides insight into processes controlling bacterial growth in this persistently oligotrophic habitat. Rates of 3H-leucine incorporation were consistently 60% greater when measured in the light than in the dark, highlighting the importance of sunlight in fueling bacterial metabolism in this ecosystem. Over diel time scales, rates of 3H-leucine incorporation were quasi-sinusoidal, with rates in the light higher near midday, while rates in the dark were greatest after sunset. Depth-integrated (0 -125 m) rates of 3H-leucine incorporation in both light and dark were more variable ( 5- and 4-fold, respectively) than coincident measurements of primary production ( 2-fold). On average, rates of bacterial production averaged 2 and 4% of primary production (in the dark and light, respectively). At near-monthly time scales, rates of 3H-leucine incorporation in both light and dark were significantly related to temperature. Our results suggest that in the subtropical oligotrophic Pacific, bacterial production appears decoupled from primary production as a result of seasonal-scale variations in temperature and light.

Folding of guanine quadruplex molecules-funnel-like mechanism or kinetic partitioning? An overview from MD simulation studies.

PubMed

Šponer, Jiří; Bussi, Giovanni; Stadlbauer, Petr; Kührová, Petra; Banáš, Pavel; Islam, Barira; Haider, Shozeb; Neidle, Stephen; Otyepka, Michal

2017-05-01

Guanine quadruplexes (GQs) play vital roles in many cellular processes and are of much interest as drug targets. In contrast to the availability of many structural studies, there is still limited knowledge on GQ folding. We review recent molecular dynamics (MD) simulation studies of the folding of GQs, with an emphasis paid to the human telomeric DNA GQ. We explain the basic principles and limitations of all types of MD methods used to study unfolding and folding in a way accessible to non-specialists. We discuss the potential role of G-hairpin, G-triplex and alternative GQ intermediates in the folding process. We argue that, in general, folding of GQs is fundamentally different from funneled folding of small fast-folding proteins, and can be best described by a kinetic partitioning (KP) mechanism. KP is a competition between at least two (but often many) well-separated and structurally different conformational ensembles. The KP mechanism is the only plausible way to explain experiments reporting long time-scales of GQ folding and the existence of long-lived sub-states. A significant part of the natural partitioning of the free energy landscape of GQs comes from the ability of the GQ-forming sequences to populate a large number of syn-anti patterns in their G-tracts. The extreme complexity of the KP of GQs typically prevents an appropriate description of the folding landscape using just a few order parameters or collective variables. We reconcile available computational and experimental studies of GQ folding and formulate basic principles characterizing GQ folding landscapes. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio. Copyright © 2016 Elsevier B.V. All rights reserved.

Large-scale mechanical buckle fold development and the initiation of tensile fractures

NASA Astrophysics Data System (ADS)

Eckert, Andreas; Connolly, Peter; Liu, Xiaolong

2014-11-01

failure associated with buckle folding is commonly associated to the distribution of outer arc extension but has also been observed on fold limbs. This study investigates whether tensile stresses and associated failure can be explained by the process of buckling under realistic in situ stress conditions. A 2-D plane strain finite element modeling approach is used to study single-layer buckle folds with a Maxwell viscoelastic rheology. A variety of material parameters are considered and their influence on the initiation of tensile stresses during the various stages of deformation is analyzed. It is concluded that the buckling process determines the strain distribution within the fold layer but is not solely responsible for the initiation of tensile stresses. The modeling results show that tensile stresses are most dependent on the permeability, viscosity, and overburden thickness. Low permeability (<10-19 m2), high viscosity (≥1021 Pa s), and low overburden pressure can explain tensile failure at the fold hinge. Tensile stresses in the limb of the fold cannot (in general) be explained by buckling. Rather, it develops due to a combination of compression and erosional unloading. The modeling results show that erosion of high permeability rocks can explain the generation of tensile stresses at significant depths (˜2 km) both at the hinge of the fold and throughout the limb of the fold. This study shows that tensile stresses and associated failure within buckle folds is directly dependent on the distribution of material parameters but moreover to the strain history of the geologic system.

Projecting large-scale area changes in land use and land cover for terrestrial carbon analyses.

Treesearch

Ralph J. Alig; Brett J. Butler

2004-01-01

One of the largest changes in US forest type areas over the last half-century has involved pine types in the South. The area of planted pine has increased more than 10-fold since 1950, mostly on private lands. Private landowners have responded to market incentives and government programs, including subsidized afforestation on marginal agricultural land. Timber harvest...

Improved luciferase gene expression using ultrasound targeted microbubble destruction therapy in swine

NASA Astrophysics Data System (ADS)

Noble, Misty L.; Song, Shuxian; Sun, Ryan R.; Fan, Luping; DiBlasi, Robert M.; O'Kelly-Priddy, Colleen; Loeb, Keith R.; Miao, Carol H.

2012-11-01

Ultrasound (US) targeted microbubble (MB) destruction (UTMD) has been shown to be an effective method in delivering drugs and plasmid DNA (pDNA) into cells. We previously reported successful gene transfection of a reporter luciferase gene, pGL4, into livers of mice and rats using UTMD. The challenge is to translate and achieve similar gene expression in large animals, like swine, where the treated tissue volume is substantially larger. The scale-up study requires proportionally increased amount of pDNA/MBs delivered to tissues and an equivalent increase in US energy. We use different MBs and surgical strategies to retain most of pDNA/MB locally during US application in order to maximize the effect of UTMD in gene transfection. Our results show significant increase in luciferase expression in swine injected with MBs and exposed to 2.7 MPa US. We obtained up to 1800-fold enhancement in the pig experiment using Definity® MBs, and 2000-fold and 6300-fold enhancement in two pig studies using RN18 MBs compared to sham. These results represent an important developmental step towards US mediated gene delivery in large animals and clinical trials.

A new dune-dwelling lizard of the genus Leiocephalus (Iguania, Leiocephalidae) from the Dominican Republic.

PubMed

Köhler, Gunther; Bobadilla, Marcos J Rodríguez; Hedges, S Blair

2016-06-13

We describe a new species of Leiocephalus from the coastal dunes of Bahía de las Calderas in the southwestern Dominican Republic. In external morphology, Leiocephalus sixtoi sp. nov. is most similar to L. schreibersii and L. inaguae. Leiocephalus sixtoi differs from L. inaguae in having a U-shaped bony parietal table (vs. V-shaped in L. inaguae), 3 or 4 enlarged postcloacal scales in males (vs. 2 in L. inaguae), most scales on snout posterior to internasal scales rugose to keeled scales (vs. smooth in L. inaguae), and a patternless throat in males, spots on the throat in females (vs. throat with dark streaks and bars in males and females of L. inaguae). Leiocephalus sixtoi differs from L. schreibersii in having the scales of the lateral fold only slightly smaller than adjacent scales (vs. scales of lateral fold distinctly smaller than adjacent scales), having prominent caudal crest scales in adult males (vs. caudal crest scales of moderate size, even in very large males in L. schreibersii), a pattern of dark gray bars on a grayish brown background in the region above the lateral body fold (vs. dense turquoise blue mottling with heavy suffusion of red pigment in L. schreibersii), a darker dorsal ground color (vs. paler in L. schreibersii), and a red iris in adult males (vs. pale grayish blue in adult male L. schreibersii). Leiocephalus sixtoi differs further from L. schreibersii in several osteological characters as follows: in L. sixtoi the nasal process of the premaxilla reaches to mid-level of the bony external nares (vs. to level of posterior margin of the bony external nares in L. schreibersii), lacking a constriction at the base of the nasal process of the premaxilla (vs. such a constriction present in L. schreibersii), and having a reduced nasal-prefrontal contact leaving the nasal processes of the frontal bone exposed (vs. nasal and prefrontal bones contact one another, thereby obscuring the nasal processes of the frontal bone in L. schreibersii). We designate SMF 26228, an adult male from Saint Marc, Province Artibonite, Haiti, as the neotype of L. schreibersii.

Syn-Extensional Constrictional Folding of the Gwoira Rider Block, a Large Fault-Bounded Slice Atop the Mai'iu Low-Angle Normal Fault, Woodlark Rift.

NASA Astrophysics Data System (ADS)

Little, T. A.; Webber, S. M.; Norton, K. P.; Mizera, M.; Oesterle, J.; Ellis, S. M.

2016-12-01

The Mai'iu Fault is an active and corrugated low-angle normal fault (LANF) in Woodlark Rift, Eastern Papua New Guinea, which dips 21° NNE, accommodating rapid N-S extension. The Gwoira rider block is a large fault-bounded sedimentary slice comprising the Gwoira Conglomerate, located within a large synformal megamullion in the Mai'iu Fault surface. The Gwoira Conglomerate was originally deposited on the Mai'iu Fault hanging wall concurrent with extension, and has since been buried to a maximum depth of 1600-2100 m (evidenced by vitrinite reflectance data), back-tilted, and synformally folded. Both the Gwoira Conglomerate (former hanging wall) and mylonitic foliation (footwall) of the Mai'iu Fault have been shortened E-W, perpendicular to the extension direction. We show that E-W synformal folding of the Gwoira Conglomerate was concurrent with ongoing sedimentation and extension on the Mai'iu Fault. Structurally shallower Gwoira Conglomerate strata are folded less than deeper strata, indicating that folding was progressively accrued concurrent with N-S extension. We also show that abandonment of the inactive strand of the Mai'iu Fault in favor of the Gwoira Fault, which resulted in formation of the Gwoira rider block, occurred in response to progressive megamullion amplification and resultant misorientation of the inactive strand of the Mai'iu Fault. We attribute E-W folding to extension-perpendicular constriction. This is consistent with observations of outcrop-scale conjugate strike-slip faults that deform the footwall and hanging wall of the Mai'iu Fault, and accommodate E-W shortening. Constrictional folding remains active in the near-surface as evidenced by synformal tilting of inferred Late Quaternary fluvial terraces atop the Gwoira rider block. This sequence of progressive constrictional folding is dated using 26Al/10Be terrestrial cosmogenic nuclide burial dating of the Gwoira Conglomerate. Finally, because rider block formation records abandonment of the uppermost part of a LANF, Coulomb fault mechanical analysis (after Choi and Buck, 2012) can be applied to field observations to provide an upper limit on LANF frictional strength (µf). Modelling constrains the µf for the Mai'iu Fault to ≤0.25, which suggests that the Mai'iu Fault is frictionally very weak.

Folds on Europa: implications for crustal cycling and accommodation of extension.

PubMed

Prockter, L M; Pappalardo, R T

2000-08-11

Regional-scale undulations with associated small-scale secondary structures are inferred to be folds on Jupiter's moon Europa. Formation is consistent with stresses from tidal deformation, potentially triggering compressional instability of a region of locally high thermal gradient. Folds may compensate for extension elsewhere on Europa and then relax away over time.

Geometry and Kinematics of the Lamu Basin Deep-Water Fold-and-Thrust Belt (East Africa)

NASA Astrophysics Data System (ADS)

Barchi, Massimiliano R.; Cruciani, Francesco; Porreca, Massimiliano

2016-04-01

Even if most thin-skinned fold-and-thrust belt are generated at convergent plate boundaries, in the last decades advances in seismic exploration and acquisition of large datasets have shown that they are also notably widespread along continental passive margins, driven by gravity processes in deep-water areas. In this study a composite set of modern and vintage reprocessed seismic reflection profiles is used to investigate the internal structure and kinematic evolution of the Lamu Basin Deep-Water Fold-and-Trust Belt (DW-FTB). The Lamu Basin is an example of giant-scale, gravity driven compressional belt developed in Late Cretaceous-Early Tertiary along a still poorly explored sector of the East-African continental margin, at the Kenya-Somalia border. The compressional domain extends longitudinally for more than 450 km, is up to 180 km wide and shows remarkable structural complexity both along strike and along dip. The external part is dominated by ocean-verging imbricate thrusts, above a gently landward-dipping basal detachment. The internal part is characterised by almost symmetrical detachment folds and double verging structures, sustaining bowl-shaped syn-tectonic basins. Here the basal detachment surface is almost flat. The mean fold wavelength displays a progressive landward increase, from 2.5 km, at the toe of the belt, to about 10 km. This structural variability is thought to be related to the lateral variation of the section under shortening and particularly to the different thickness of the Early Cretaceous shaly unit involved in the deformations, increasing landward from about 400 m to more than 1 km. Through the sequential restoration of regional cross-sections, we evaluated that the northern portion of the thrust belt experienced a shortening of almost 50 km (corresponding to 20%), with a shortening rate (during the Late Cretaceous-Paleocene main event) of about 3.5 mm/yr. Under many respects, the dimensions and internal structure of this thrust belt are comparable to that of analogue-scaled structures, developed at convergent plate boundaries, e.g. the foreland fold-and-trust belts. However, its kinematic evolution shows some peculiar characters: shortening seems largely synchronous across the whole thrust belt and the maximum shortening is achieved in its frontal part (toe thrust), diminishing landward.

Single-molecule studies highlight conformational heterogeneity in the early folding steps of a large ribozyme

PubMed Central

Xie, Zheng; Srividya, Narayanan; Sosnick, Tobin R.; Pan, Tao; Scherer, Norbert F.

2004-01-01

The equilibrium folding of the catalytic domain of Bacillus subtilis RNase P RNA is investigated by single-molecule fluorescence resonance energy transfer (FRET). Previous ensemble studies of this 255-nucleotide ribozyme described the equilibrium folding with two transitions, U-to-Ieq-to-N, and focused on the Ieq-to-N transition. The present study focuses on the U-to-Ieq transition. Comparative ensemble measurements of the ribozyme construct labeled with fluorescein at the 5′ end and Cy3 at the 3′ end show that modifications required for labeling do not interfere with folding and help to define the Mg2+ concentration range for the U-to-Ieq transition. Histogram analysis of the Mg2+-dependent single-molecule FRET efficiency reveals two previously undetermined folding intermediates. The single-molecule FRET trajectories exhibit non-two-state and nonergodic behaviors at intermediate Mg2+ concentrations on the time scale of seconds. The trajectories at intermediate Mg2+ concentrations are classified into five classes based on three FRET levels and their dynamics of interconversion within the measured time range. This heterogeneity, together with the observation of “nonsudden jump” FRET transitions, indicates that the early folding steps of this ribozyme involve a series of intermediates with different degrees of kinetic isolation and that folding occurs under kinetic control and involves many “local” conformational switches. A free energy contour is constructed to illustrate the complex folding surface. PMID:14704266

A dose-response relationship between exposure to a large-scale HIV preventive intervention and consistent condom use with different sexual partners of female sex workers in southern India.

PubMed

Deering, Kathleen N; Boily, Marie-Claude; Lowndes, Catherine M; Shoveller, Jean; Tyndall, Mark W; Vickerman, Peter; Bradley, Jan; Gurav, Kaveri; Pickles, Michael; Moses, Stephen; Ramesh, Banadakoppa M; Washington, Reynold; Rajaram, S; Alary, Michel

2011-12-29

The Avahan Initiative, a large-scale HIV preventive intervention targeted to high-risk populations including female sex workers (FSWs), was initiated in 2003 in six high-prevalence states in India, including Karnataka. This study assessed if intervention exposure was associated with condom use with FSWs' sexual partners, including a dose-response relationship. Data were from a cross-sectional study (2006-07) of 775 FSWs in three districts in Karnataka. Survey methods accounted for the complex cluster sampling design. Bivariate and multivariable logistic regression was used to separately model the relationships between each of five intervention exposure variables and five outcomes for consistent condom use (CCU= always versus frequently/sometimes/never) with different sex partners, including with: all clients; occasional clients; most recent repeat client; most recent non-paying partner; and the husband or cohabiting partner. Linear tests for trends were conducted for three continuous intervention exposure variables. FSWs reported highest CCU with all clients (81.7%); CCU was lowest with FSWs' husband or cohabiting partner (9.6%). In multivariable analysis, the odds of CCU with all clients and with occasional clients were 6.3-fold [95% confidence intervals, CIs: 2.8-14.5] and 2.3-fold [95% CIs: 1.4-4.1] higher among FSWs contacted by intervention staff and 4.9-fold [95% CIs: 2.6-9.3] and 2.3-fold [95% CIs: 1.3-4.1] higher among those who ever observed a condom demonstration by staff, respectively, compared to those who had not. A significant dose-response relationship existed between each of these CCU outcomes and increased duration since first contacted by staff (P=0.001; P=0.006) and numbers of condom demonstrations witnessed (P=0.004; P=0.026); a dose-response relationship was also observed between condom use with all clients and number of times contacted by staff (P=0.047). Intervention exposure was not associated with higher odds of CCU with the most recent repeat client, most recent non-paying partner or with the husband or cohabiting partner. Study findings suggest that exposure to a large-scale HIV intervention for FSWs was associated with increased CCU with commercial clients. Moreover, there were dose-response relationships between CCU with clients and increased duration since first contacted by staff, times contacted by staff and number of condom demonstrations. Additional program effort is required to increase condom use with non-commercial partners.

A dose-response relationship between exposure to a large-scale HIV preventive intervention and consistent condom use with different sexual partners of female sex workers in southern India

PubMed Central

2011-01-01

Background The Avahan Initiative, a large-scale HIV preventive intervention targeted to high-risk populations including female sex workers (FSWs), was initiated in 2003 in six high-prevalence states in India, including Karnataka. This study assessed if intervention exposure was associated with condom use with FSWs’ sexual partners, including a dose-response relationship. Methods Data were from a cross-sectional study (2006-07) of 775 FSWs in three districts in Karnataka. Survey methods accounted for the complex cluster sampling design. Bivariate and multivariable logistic regression was used to separately model the relationships between each of five intervention exposure variables and five outcomes for consistent condom use (CCU= always versus frequently/sometimes/never) with different sex partners, including with: all clients; occasional clients; most recent repeat client; most recent non-paying partner; and the husband or cohabiting partner. Linear tests for trends were conducted for three continuous intervention exposure variables. Results FSWs reported highest CCU with all clients (81.7%); CCU was lowest with FSWs’ husband or cohabiting partner (9.6%). In multivariable analysis, the odds of CCU with all clients and with occasional clients were 6.3-fold [95% confidence intervals, CIs: 2.8-14.5] and 2.3-fold [95% CIs: 1.4-4.1] higher among FSWs contacted by intervention staff and 4.9-fold [95% CIs: 2.6-9.3] and 2.3-fold [95% CIs: 1.3-4.1] higher among those who ever observed a condom demonstration by staff, respectively, compared to those who had not. A significant dose-response relationship existed between each of these CCU outcomes and increased duration since first contacted by staff (P=0.001; P=0.006) and numbers of condom demonstrations witnessed (P=0.004; P=0.026); a dose-response relationship was also observed between condom use with all clients and number of times contacted by staff (P=0.047). Intervention exposure was not associated with higher odds of CCU with the most recent repeat client, most recent non-paying partner or with the husband or cohabiting partner. Conclusion Study findings suggest that exposure to a large-scale HIV intervention for FSWs was associated with increased CCU with commercial clients. Moreover, there were dose-response relationships between CCU with clients and increased duration since first contacted by staff, times contacted by staff and number of condom demonstrations. Additional program effort is required to increase condom use with non-commercial partners. PMID:22375863

Dragons in the mist: three new species of Pseudocalotes Fitzinger (Squamata: Agamidae) from the sky island archipelago of Peninsular Malaysia.

PubMed

Grismer, L Lee; Quah, Evan S H; Wood, Perry L Jr; Anuar, Shahrul; Muin, Abdul; Davis, Hayden R; Murdoch, Matthew L; Grismer, Jesse L; Cota, Michael; Cobos, Anthony J

2016-07-07

An integrative taxonomic analysis is used to delimit and describe three new species of Pseudocalotoes from the sky island archipelago of the Banjaran (=mountain range) Titiwangsa of Peninsular Malaysia. Pseudocalotes drogon sp. nov., from Fraser's Hill, Pahang is basal to the sister species P. larutensis from Bukit Larut, Perak in the Banjaran Bintang and the new species P. rhaegal sp. nov. from Cameron Highlands, Pahang. Pseudocalotes drogon sp. nov. is differentiated from all other species of Psuedocalotes by having the combination of a flat rostrum; seven postrostrals; an interparietal; 11 circumorbitals; five canthals; 7-10 superciliaries; one scale between the rostral and nasal; nine supralabials; eight infralabials; 10 postnasal-suborbital scales; four postmentals; five or six sublabials; five or six chinshields; 47 smooth, wide, gular scales; weak transverse gular and antehumeral folds; two enlarged scales between the ear and eye; enlarged upper and lower posttemporals; a single enlarged supratympanic; no enlarged postrictals; three large scales bordering the dorsal margin of the ear opening; large pretympanic scales; eight scales in the nuchal crest not separated by a gap; enlarged vertebral scales extending to the tip of the tail; keeled and non-plate-like scales on flanks; 51 midbody scales; midventrals smaller than dorsals; 19 subdigital lamellae on the fourth finger; 23 subdigital lamellae on the fourth toe; preaxial scales on third toe enlarged and spinose; subdigital lamellae not unicarinate; HW/HL 0.52; HL/SVL 0.31; no elbow or knee patches; and a male dewlap color of lime-green bearing a central yellow spot. Pseudocalotes rhaegal sp. nov. is differentiated from all other Psuedocalotes by having the combination of a convex rostrum; 6-8 postrostrals; an interparietal; nine or 10 circumorbitals; five canthals; 7-10 superciliaries; one or two scales between the rostral and nasal scales; eight or nine supralabials; seven or eight infralabials; 11 or 12 postnasal-suborbital scales; four postmentals; four or five chinshields; 40-45 smooth, wide, gular scales; no transverse gular fold; a weak antehumeral fold; three or four enlarged scales between the ear and eye; an enlarged upper and lower posttemporal; an enlarged supratympanic; no enlarged postrictals; no large scales bordering the upper margin of the ear opening or in the pretympanic region; 6-8 enlarged nuchal crest scales not separated by a gap; enlarged vertebral scales extending to the base of the tail; weakly keeled, non-plate-like scales on the flanks; 52-58 midbody scales; midventrals smaller than dorsals; 19-21 subdigital lamellae on the fourth finger; 22-26 subdigital lamellae on the fourth toe; preaxial scales on the third enlarged and rounded; subdigital lamellae not unicarinate; HW/HL 0.50-0.54; HL/SVL 0.28-0.30; no elbow or knee patches; and female dewlap color yellow bearing a purple base. The analyses also indicated that the new species, P. viserion sp. nov. from Genting Highlands, Pahang in the southern section of the Banjaran Titiwangsa is the sister species of P. flavigula from Cameron Highlands 121 km to the north and can be separated from all other species of Psuedocalotes by having the combination of three postrostrals; 10 circumorbitals; four or five canthals; 5-7 superciliaries; rostral and nasals in contact; supralabials contacting the nasal; six or seven supralabials; six or seven infralabials; two or three postmentals; 47 or 48 smooth, flat, gular scales; three chinshields; weak transverse gular and antehumeral folds; two enlarged scales between the ear and eye; an enlarged upper and lower posttemporal; an enlarged supratympanic; no enlarged postrictals; 7-9 nuchal crest scales lacking gaps and not extending beyond midbody; weakly keeled and plate-like scales on the flanks; 35-38 midbody scales; ventrals smaller than dorsals; 22 or 23 subdigital lamellae on the fourth finger; 26 or 27 subdigital lamellae on the fourth toe; preaxial scales on the third toe not modified; subdigital scales not unicarinate; HW/HL 0.62; no white marking below the eye; dewlap in males yellow; and no elbow or knee patches. Pseudocalotes rhaegal sp. nov. most likely occurs in syntopy with P. flavigula in Tanah Rata at Cameron Highlands and its discovery adds to a growing body of literature detailing the recent descriptions of several new, upland, closely related, sympatric species in Peninsular Malaysia. Another new population referred to here as Pseudocalotes sp. nov. from the Hala-Bala Wildlife Sanctuary, Betong District, Yala Province, Thailand is discussed. The discovery and description of these three new Pseudocalotes from the upland regions of Peninsular Malaysia continues to underscore the remarkably high herpetological diversity and ecological complexity in this sky island archipelago that is still underestimated, unappreciated, and unprotected.

Possible origin of the Bighorn uplift, WY, by lithospheric buckling during the Laramide orogeny

NASA Astrophysics Data System (ADS)

Tikoff, B.; Siddoway, C. S.; Worthington, L. L.; Anderson, M. L.

2017-12-01

The EarthScope Bighorn Project investigated the Bighorn uplift, Wyoming, a foreland structure developed during the 75-55 Ma Laramide orogeny. Any model for the Bighorn uplift must account for several geological and geophysical results from the EarthScope broadband and passive-active seismic study, the broader context provided by USArray, and legacy datasets: 1) The Moho is bulged up below portions of the surface exposure of the basement arch; 2) a high-velocity, high-density material (the "7.x layer") is absent in the lower crust beneath the arch culmination; 3) Shear wave splitting analysis shows distinct mantle fabrics on either side of the uplift; 4) Crustal thicknesses varied widely prior to the Laramide-age deformation; 5) A lack of reflectors associated with a regional decollement; 6) The Bighorn arch forms one in an array of low-amplitude, large-wavelength folds throughout the High Plains region. The uplift borders a NNW-trending (E-dipping?) geophysical anomaly inferred to be Proterozoic suture. A lithospheric buckling model offers a framework that accommodates most of the geological and geophysical data. Lithospheric buckling is the concept of low-amplitude, large-wavelength (150-350 km) lithospheric folding developed in response to an end-load, replicated in scaled physical models. A buckling instability focuses initial deformation, with faults developed in layered media/crustal section as shortening progresses. The strength/age of the mantle controls the fold wavelength, based on examples from multiple orogens (e.g. Urals, central Asia). Rarely does the geometry of the upward Moho deflection identically mirror the surface uplift in scaled models, nor does it in the Bighorn uplift, where fold localization is likely controlled by a pre-existing Proterozoic suture and/or mantle asperity. Indicated by shear wave SKS splitting data, distinct mantle fabrics on either side of the uplift extend into the lithospheric mantle, indicated the presence of a deep-rooted structure of a type that has not been incorporated in physical models.

On the necessity of dissecting sequence similarity scores into segment-specific contributions for inferring protein homology, function prediction and annotation

PubMed Central

2014-01-01

Background Protein sequence similarities to any types of non-globular segments (coiled coils, low complexity regions, transmembrane regions, long loops, etc. where either positional sequence conservation is the result of a very simple, physically induced pattern or rather integral sequence properties are critical) are pertinent sources for mistaken homologies. Regretfully, these considerations regularly escape attention in large-scale annotation studies since, often, there is no substitute to manual handling of these cases. Quantitative criteria are required to suppress events of function annotation transfer as a result of false homology assignments. Results The sequence homology concept is based on the similarity comparison between the structural elements, the basic building blocks for conferring the overall fold of a protein. We propose to dissect the total similarity score into fold-critical and other, remaining contributions and suggest that, for a valid homology statement, the fold-relevant score contribution should at least be significant on its own. As part of the article, we provide the DissectHMMER software program for dissecting HMMER2/3 scores into segment-specific contributions. We show that DissectHMMER reproduces HMMER2/3 scores with sufficient accuracy and that it is useful in automated decisions about homology for instructive sequence examples. To generalize the dissection concept for cases without 3D structural information, we find that a dissection based on alignment quality is an appropriate surrogate. The approach was applied to a large-scale study of SMART and PFAM domains in the space of seed sequences and in the space of UniProt/SwissProt. Conclusions Sequence similarity core dissection with regard to fold-critical and other contributions systematically suppresses false hits and, additionally, recovers previously obscured homology relationships such as the one between aquaporins and formate/nitrite transporters that, so far, was only supported by structure comparison. PMID:24890864

Smart Kirigami open honeycombs in shape changing actuation and dynamics

NASA Astrophysics Data System (ADS)

Neville, R. M.; Scarpa, F.; Leng, J.

2017-04-01

Kirigami is the ancient Japanese art of cutting and folding paper, widespread in Asia since the 17th century. Kirigami offers a broader set of geometries and topologies than classical fold/valleys Origami, because of the presence of cuts. Moreover, Kirigami can be readily applied to a large set of composite and smart 2D materials, and can be used to up-scaled productions with modular molding. We describe the manufacturing and testing of a topology of Kirigami cellular structures defined as Open Honeycombs. Open Honeycombs (OHs) can assume fully closed shape and be alike classical hexagonal centresymmetric honeycombs, or can vary their morphology by tuning the opening angle and rotational stiffness of the folds. We show the performance of experimental PEEK OHs with cable actuation and morphing shape characteristics, and the analogous morphing behavior of styrene SMPs under combined mechanical and thermal loading. We also show the dynamic (modal analysis) behavior of OHs configurations parameterized against their geometry characteristics, and the controllable modal density characteristics that one could obtain by tuning the topology and folding properties.

Influence of scale-dependent fracture intensity on block size distribution and rock slope failure mechanisms in a DFN framework

NASA Astrophysics Data System (ADS)

Agliardi, Federico; Galletti, Laura; Riva, Federico; Zanchi, Andrea; Crosta, Giovanni B.

2017-04-01

An accurate characterization of the geometry and intensity of discontinuities in a rock mass is key to assess block size distribution and degree of freedom. These are the main controls on the magnitude and mechanisms of rock slope instabilities (structurally-controlled, step-path or mass failures) and rock mass strength and deformability. Nevertheless, the use of over-simplified discontinuity characterization approaches, unable to capture the stochastic nature of discontinuity features, often hampers a correct identification of dominant rock mass behaviour. Discrete Fracture Network (DFN) modelling tools have provided new opportunities to overcome these caveats. Nevertheless, their ability to provide a representative picture of reality strongly depends on the quality and scale of field data collection. Here we used DFN modelling with FracmanTM to investigate the influence of fracture intensity, characterized on different scales and with different techniques, on the geometry and size distribution of generated blocks, in a rock slope stability perspective. We focused on a test site near Lecco (Southern Alps, Italy), where 600 m high cliffs in thickly-bedded limestones folded at the slope scale impend on the Lake Como. We characterized the 3D slope geometry by Structure-from-Motion photogrammetry (range: 150-1500m; point cloud density > 50 pts/m2). Since the nature and attributes of discontinuities are controlled by brittle failure processes associated to large-scale folding, we performed a field characterization of meso-structural features (faults and related kinematics, vein and joint associations) in different fold domains. We characterized the discontinuity populations identified by structural geology on different spatial scales ranging from outcrops (field surveys and photo-mapping) to large slope sectors (point cloud and photo-mapping). For each sampling domain, we characterized discontinuity orientation statistics and performed fracture mapping and circular window analyses in order to measure fracture intensity (P21) and persistence (trace length distributions). Then, we calibrated DFN models for different combinations of P21/P32 and trace length distributions, characteristic of data collected on different scale. Comparing fracture patterns and block size distributions obtained from different models, we outline the strong influence of field data quality and scale on the rock mass behaviours predicted by DFN. We show that accounting for small scale features (close but short fractures) results in smaller but more interconnected blocks, eventually characterized by low removability and partly supported by intact rock strength. On the other hand, DFN based on data surveyed on slope scale enhance the structural control of persistent fracture on the kinematic degree-of freedom of medium-sized blocks, with significant impacts on the selection and parametrization of rock slope stability modelling approaches.

Multiple scales and phases in discrete chains with application to folded proteins

NASA Astrophysics Data System (ADS)

Sinelnikova, A.; Niemi, A. J.; Nilsson, Johan; Ulybyshev, M.

2018-05-01

Chiral heteropolymers such as large globular proteins can simultaneously support multiple length scales. The interplay between the different scales brings about conformational diversity, determines the phase properties of the polymer chain, and governs the structure of the energy landscape. Most importantly, multiple scales produce complex dynamics that enable proteins to sustain live matter. However, at the moment there is incomplete understanding of how to identify and distinguish the various scales that determine the structure and dynamics of a complex protein. Here we address this impending problem. We develop a methodology with the potential to systematically identify different length scales, in the general case of a linear polymer chain. For this we introduce and analyze the properties of an order parameter that can both reveal the presence of different length scales and can also probe the phase structure. We first develop our concepts in the case of chiral homopolymers. We introduce a variant of Kadanoff's block-spin transformation to coarse grain piecewise linear chains, such as the C α backbone of a protein. We derive analytically, and then verify numerically, a number of properties that the order parameter can display, in the case of a chiral polymer chain. In particular, we propose that in the case of a chiral heteropolymer the order parameter can reveal traits of several different phases, contingent on the length scale at which it is scrutinized. We confirm that this is the case with crystallographic protein structures in the Protein Data Bank. Thus our results suggest relations between the scales, the phases, and the complexity of folding pathways.

Large-scale two-photon imaging revealed super-sparse population codes in the V1 superficial layer of awake monkeys.

PubMed

Tang, Shiming; Zhang, Yimeng; Li, Zhihao; Li, Ming; Liu, Fang; Jiang, Hongfei; Lee, Tai Sing

2018-04-26

One general principle of sensory information processing is that the brain must optimize efficiency by reducing the number of neurons that process the same information. The sparseness of the sensory representations in a population of neurons reflects the efficiency of the neural code. Here, we employ large-scale two-photon calcium imaging to examine the responses of a large population of neurons within the superficial layers of area V1 with single-cell resolution, while simultaneously presenting a large set of natural visual stimuli, to provide the first direct measure of the population sparseness in awake primates. The results show that only 0.5% of neurons respond strongly to any given natural image - indicating a ten-fold increase in the inferred sparseness over previous measurements. These population activities are nevertheless necessary and sufficient to discriminate visual stimuli with high accuracy, suggesting that the neural code in the primary visual cortex is both super-sparse and highly efficient. © 2018, Tang et al.

The effect of UV light on the inactivation of Giardia lamblia and Giardia muris cysts as determined by animal infectivity assay (P-2951-01).

PubMed

Mofidi, Alexander A; Meyer, Ernest A; Wallis, Peter M; Chou, Connie I; Meyer, Barbara P; Ramalingam, Shivaji; Coffey, Bradley M

2002-04-01

This study measured the effect of germicidal ultraviolet (UV) light on Giardia lamblia and Giardia muris cysts, as determined by their infectivity in Mongolian gerbils and CD-1 mice, respectively. Reduction of cyst infectivity due to UV exposure was quantified by applying most probable number techniques. Controlled bench-scale, collimated-beam tests exposed cysts suspended in filtered natural water to light from a low-pressure UV lamp. Both G. lamblia and G. muris cysts showed similar sensitivity to UV light. At 3 mJ/cm2, a dose 10-fold lower than what large-scale UV reactors may be designed to provide, > 2-log10 (99 percent) inactivation was observed. These results, combined with previously published data showing other protozoa and bacteria have similar, high sensitivity to UV light, establish that UV disinfection of drinking water is controlled by viruses which may require over 10-fold more UV dose for the same level of control.

Photosynthetic production of hydrogen. [Blue-green alga, Anabaena cylindrica

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

Neil, G.; Nicholas, D.J.D.; Bockris, J.O.

A systematic investigation of photosynthetic hydrogen production using a blue-green alga, Anabaena cylindrica, was carried out. The results indicate that there are two important problems which must be overcome for large-scale hydrogen production using photosynthetic processes. These are (a) the development of a stable system, and (b) attainment of at least a fifty-fold increase in the rate of hydrogen evolution per unit area illuminated.

Integrated process development-a robust, rapid method for inclusion body harvesting and processing at the microscale level.

PubMed

Walther, Cornelia; Kellner, Martin; Berkemeyer, Matthias; Brocard, Cécile; Dürauer, Astrid

2017-10-21

Escherichia coli stores large amounts of highly pure product within inclusion bodies (IBs). To take advantage of this beneficial feature, after cell disintegration, the first step to optimal product recovery is efficient IB preparation. This step is also important in evaluating upstream optimization and process development, due to the potential impact of bioprocessing conditions on product quality and on the nanoscale properties of IBs. Proper IB preparation is often neglected, due to laboratory-scale methods requiring large amounts of materials and labor. Miniaturization and parallelization can accelerate analyses of individual processing steps and provide a deeper understanding of up- and downstream processing interdependencies. Consequently, reproducible, predictive microscale methods are in demand. In the present study, we complemented a recently established high-throughput cell disruption method with a microscale method for preparing purified IBs. This preparation provided results comparable to laboratory-scale IB processing, regarding impurity depletion, and product loss. Furthermore, with this method, we performed a "design of experiments" study to demonstrate the influence of fermentation conditions on the performance of subsequent downstream steps and product quality. We showed that this approach provided a 300-fold reduction in material consumption for each fermentation condition and a 24-fold reduction in processing time for 24 samples.

Earthquakes and aseismic creep associated with growing fault-related folds

NASA Astrophysics Data System (ADS)

Burke, C. C.; Johnson, K. M.

2017-12-01

Blind thrust faults overlain by growing anticlinal folds pose a seismic risk to many urban centers in the world. A large body of research has focused on using fold and growth strata geometry to infer the rate of slip on the causative fault and the distribution of off-fault deformation. However, because we have had few recorded large earthquakes on blind faults underlying folds, it remains unclear how much of the folding occurs during large earthquakes or during the interseismic period accommodated by aseismic creep. Numerous kinematic and mechanical models as well as field observations demonstrate that flexural slip between sedimentary layering is an important mechanism of fault-related folding. In this study, we run boundary element models of flexural-slip fault-related folding to examine the extent to which energy is released seismically or aseismically throughout the evolution of the fold and fault. We assume a fault imbedded in viscoelastic mechanical layering under frictional contact. We assign depth-dependent frictional properties and adopt a rate-state friction formulation to simulate slip over time. We find that in many cases, a large percentage (greater than 50%) of fold growth is accomplished by aseismic creep at bedding and fault contacts. The largest earthquakes tend to occur on the fault, but a significant portion of the seismicity is distributed across bedding contacts through the fold. We are currently working to quantify these results using a large number of simulations with various fold and fault geometries. Result outputs include location, duration, and magnitude of events. As more simulations are completed, these results from different fold and fault geometries will provide insight into how much folding occurs from these slip events. Generalizations from these simulations can be compared with observations of active fault-related folds and used in the future to inform seismic hazard studies.

On the Signaling of Electrochemical Aptamer-Based Sensors: Collision- and Folding-Based Mechanisms

PubMed Central

Xiao, Yi; Uzawa, Takanori; White, Ryan J.; DeMartini, Daniel; Plaxco, Kevin W.

2010-01-01

Recent years have seen the emergence of a new class of electrochemical sensors predicated on target binding-induced folding of electrode-bound redox-modified aptamers and directed against targets ranging from small molecules to proteins. Previous studies of the relationship between gain and probe-density for these electrochemical, aptamer-based (E-AB) sensors suggest that signal transduction is linked to binding-induced changes in the efficiency with which the attached redox tag strikes the electrode. This, in turn, suggests that even well folded aptamers may support E-AB signaling if target binding sufficiently alters their flexibility. Here we investigate this using a thrombin-binding aptamer that undergoes binding-induced folding at low ionic strength but can be forced to adopt a folded conformation at higher ionic strength even in the absence of its protein target. We find that, under conditions in which the thrombin aptamer is fully folded prior to target binding, we still obtain a ca. 30% change in E-AB signal upon saturated target levels. In contrast, however, under conditions in which the aptamer is unfolded in the absence of target and thus undergoes binding-induced folding the observed signal change is twice as great. The ability of folded aptamers to support E-AB signaling, however, is not universal: a fully folded anti-IgE aptamer, for example, produces only an extremely small, ca. 2.5% signal change in the presence of target despite the larger steric bulk of this protein. Thus, while it appears that binding-induced changes in the dynamics in fully folded aptamers can support E-AB signaling, this signaling mechanism may not be general, and in order to ensure the design of high-gain sensors binding must be linked to a large-scale conformational change. PMID:20436787

Self-folding with shape memory composites at the millimeter scale

NASA Astrophysics Data System (ADS)

Felton, S. M.; Becker, K. P.; Aukes, D. M.; Wood, R. J.

2015-08-01

Self-folding is an effective method for creating 3D shapes from flat sheets. In particular, shape memory composites—laminates containing shape memory polymers—have been used to self-fold complex structures and machines. To date, however, these composites have been limited to feature sizes larger than one centimeter. We present a new shape memory composite capable of folding millimeter-scale features. This technique can be activated by a global heat source for simultaneous folding, or by resistive heaters for sequential folding. It is capable of feature sizes ranging from 0.5 to 40 mm, and is compatible with multiple laminate compositions. We demonstrate the ability to produce complex structures and mechanisms by building two self-folding pieces: a model ship and a model bumblebee.

The Generalized Born solvation model: What is it?

NASA Astrophysics Data System (ADS)

Onufriev, Alexey

2004-03-01

Implicit solvation models provide, for many applications, an effective way of describing the electrostatic effects of aqueous solvation. Here we outline the main approximations behind the popular Generalized Born solvation model. We show how its accuracy, relative to the Poisson-Boltzmann treatment, can be significantly improved in a computationally inexpensive manner to make the model useful in the studies of large-scale conformational transitions at the atomic level. The improved model is tested in a molecular dynamics simulation of folding of a 46-residue (three helix bundle) protein. Starting from an extended structure at 450K, the protein folds to the lowest energy conformation within 6 ns of simulation time, and the predicted structure differs from the native one by 2.4 A (backbone RMSD).

Folding kinematics expressed in fracture patterns: An example from the Anti-Atlas fold belt, Morocco

NASA Astrophysics Data System (ADS)

Ismat, Zeshan

2008-11-01

The Anti-Atlas fold belt, Morocco, formed during the same Variscan collisional event that produced the Valley-and-Ridge fold-thrust belt of the Appalachian mountains. Both are external belts of the Appalachian-Ouachita-Mauritanides chain and at the map scale have very similar topographic expressions. The Anti-Atlas, however, consists of map-scale folds that are buckle-related, detachment folds, whereas the Valley-and-Ridge folds developed in response to imbricate thrusting. For this reason, the Anti-Atlas is referred to as a fold belt rather than a fold-thrust belt. This paper examines Variscan folding processes in the Anti-Atlas Mountains. Folding in some layers occurred by sliding along a penetrative network of mesoscale fractures, i.e. cataclastic flow, during buckling. Layer-parallel shortening fractures were reactivated in the later stages of folding to accommodate limb rotation. Although 'boutonnieres', i.e. basement uplifts, punctuate the fold belt, the fracture patterns indicate that the uplifts failed to provide any 'bending' component. Folding is also interpreted to occur under low to moderate confining pressures because the fracture network includes conjugate shear fractures with very small (˜20°) dihedral angles.

Mechanical restoration of large-scale folded multilayers using the finite element method: Application to the Zagros Simply Folded Belt, N-Iraq

NASA Astrophysics Data System (ADS)

Frehner, Marcel; Reif, Daniel; Grasemann, Bernhard

2010-05-01

There are a large number of numerical finite element studies concerned with modeling the evolution of folded geological layers through time. This body of research includes many aspects of folding and many different approaches, such as two- and three-dimensional studies, single-layer folding, detachment folding, development of chevron folds, Newtonian, power-law viscous and more complex rheologies, influence of anisotropy, pure-shear, simple-shear and other boundary conditions and so forth. In recent years, studies of multilayer folding emerged, thanks to more advanced mesh generator software and increased computational power. Common to all of these studies is the fact that they consider a forward directed time evolution, as in nature. Very few studies use the finite element method for reverse-time simulations. In such studies, folded geological layers are taken as initial conditions for the numerical simulation. The folding process is reversed by changing the signs of the boundary conditions that supposedly drove the folding process. In such studies, the geometry of the geological layers before the folding process is searched and the amount of shortening necessary for the final folded geometry can be calculated. In contrast to a kinematic or geometric fold restoration procedure, the described approach takes the mechanical behavior of the geological layers into account, such as rheology and the relative strength of the individual layers. This approach is therefore called mechanical restoration of folds. In this study, the concept of mechanical restoration is applied to a two-dimensional 50km long NE-SW-cross-section through the Zagros Simply Folded Belt in Iraqi Kurdistan, NE from the city of Erbil. The Simply Folded Belt is dominated by gentle to open folding and faults are either absent or record only minor offset. Therefore, this region is ideal for testing the concept of mechanical restoration. The profile used is constructed from structural field measurements and digital elevation models using the dip-domain method for balancing the cross-section. The lithology consists of Cretaceous to Cenozoic sediments. Massive carbonate rock units act as the competent layers compared to the incompetent behavior of siltstone, claystone and marl layers. We show the first results of the mechanical restoration of the Zagros cross-section and we discuss advantages and disadvantages, as well as some technical aspects of the applied method. First results indicate that a shortening of at least 50% was necessary to create the present-day folded cross-section. This value is higher than estimates of the amount of shortening solely based on kinematic or geometric restoration. One particular problem that is discussed is the presence of (unnaturally) sharp edges in a balanced cross-section produced using the dip-domain method, which need to be eliminated for mechanical restoration calculations to get reasonable results.

Computational design of RNA parts, devices, and transcripts with kinetic folding algorithms implemented on multiprocessor clusters.

PubMed

Thimmaiah, Tim; Voje, William E; Carothers, James M

2015-01-01

With progress toward inexpensive, large-scale DNA assembly, the demand for simulation tools that allow the rapid construction of synthetic biological devices with predictable behaviors continues to increase. By combining engineered transcript components, such as ribosome binding sites, transcriptional terminators, ligand-binding aptamers, catalytic ribozymes, and aptamer-controlled ribozymes (aptazymes), gene expression in bacteria can be fine-tuned, with many corollaries and applications in yeast and mammalian cells. The successful design of genetic constructs that implement these kinds of RNA-based control mechanisms requires modeling and analyzing kinetically determined co-transcriptional folding pathways. Transcript design methods using stochastic kinetic folding simulations to search spacer sequence libraries for motifs enabling the assembly of RNA component parts into static ribozyme- and dynamic aptazyme-regulated expression devices with quantitatively predictable functions (rREDs and aREDs, respectively) have been described (Carothers et al., Science 334:1716-1719, 2011). Here, we provide a detailed practical procedure for computational transcript design by illustrating a high throughput, multiprocessor approach for evaluating spacer sequences and generating functional rREDs. This chapter is written as a tutorial, complete with pseudo-code and step-by-step instructions for setting up a computational cluster with an Amazon, Inc. web server and performing the large numbers of kinefold-based stochastic kinetic co-transcriptional folding simulations needed to design functional rREDs and aREDs. The method described here should be broadly applicable for designing and analyzing a variety of synthetic RNA parts, devices and transcripts.

Cellular scaling rules for the brain of Artiodactyla include a highly folded cortex with few neurons

PubMed Central

Kazu, Rodrigo S.; Maldonado, José; Mota, Bruno; Manger, Paul R.; Herculano-Houzel, Suzana

2014-01-01

Quantitative analysis of the cellular composition of rodent, primate, insectivore, and afrotherian brains has shown that non-neuronal scaling rules are similar across these mammalian orders that diverged about 95 million years ago, and therefore appear to be conserved in evolution, while neuronal scaling rules appear to be free to vary in a clade-specific manner. Here we analyze the cellular scaling rules that apply to the brain of artiodactyls, a group within the order Cetartiodactyla, believed to be a relatively recent radiation from the common Eutherian ancestor. We find that artiodactyls share non-neuronal scaling rules with all groups analyzed previously. Artiodactyls share with afrotherians and rodents, but not with primates, the neuronal scaling rules that apply to the cerebral cortex and cerebellum. The neuronal scaling rules that apply to the remaining brain areas are, however, distinct in artiodactyls. Importantly, we show that the folding index of the cerebral cortex scales with the number of neurons in the cerebral cortex in distinct fashions across artiodactyls, afrotherians, rodents, and primates, such that the artiodactyl cerebral cortex is more convoluted than primate cortices of similar numbers of neurons. Our findings suggest that the scaling rules found to be shared across modern afrotherians, glires, and artiodactyls applied to the common Eutherian ancestor, such as the relationship between the mass of the cerebral cortex as a whole and its number of neurons. In turn, the distribution of neurons along the surface of the cerebral cortex, which is related to its degree of gyrification, appears to be a clade-specific characteristic. If the neuronal scaling rules for artiodactyls extend to all cetartiodactyls, we predict that the large cerebral cortex of cetaceans will still have fewer neurons than the human cerebral cortex. PMID:25429261

Unconstrained Structure Formation in Coarse-Grained Protein Simulations

NASA Astrophysics Data System (ADS)

Bereau, Tristan

The ability of proteins to fold into well-defined structures forms the basis of a wide variety of biochemical functions in and out of the cell membrane. Many of these processes, however, operate at time- and length-scales that are currently unattainable by all-atom computer simulations. To cope with this difficulty, increasingly more accurate and sophisticated coarse-grained models are currently being developed. In the present thesis, we introduce a solvent-free coarse-grained model for proteins. Proteins are modeled by four beads per amino acid, providing enough backbone resolution to allow for accurate sampling of local conformations. It relies on simple interactions that emphasize structure, such as hydrogen bonds and hydrophobicity. Realistic alpha/beta content is achieved by including an effective nearest-neighbor dipolar interaction. Parameters are tuned to reproduce both local conformations and tertiary structures. By studying both helical and extended conformations we make sure the force field is not biased towards any particular secondary structure. Without any further adjustments or bias a realistic oligopeptide aggregation scenario is observed. The model is subsequently applied to various biophysical problems: (i) kinetics of folding of two model peptides, (ii) large-scale amyloid-beta oligomerization, and (iii) protein folding cooperativity. The last topic---defined by the nature of the finite-size thermodynamic transition exhibited upon folding---was investigated from a microcanonical perspective: the accurate evaluation of the density of states can unambiguously characterize the nature of the transition, unlike its corresponding canonical analysis. Extending the results of lattice simulations and theoretical models, we find that it is the interplay between secondary structure and the loss of non-native tertiary contacts which determines the nature of the transition. Finally, we combine the peptide model with a high-resolution, solvent-free, lipid model. The lipid force field was systematically tuned to reproduce the structural and mechanical properties of phosphatidylcholine bilayers. The two models were cross-parametrized against atomistic potential of mean force curves for the insertion of single amino acid side chains into a bilayer. Coarse-grained transmembrane protein simulations were then compared with experiments and atomistic simulations to validate the force field. The transferability of the two models across amino acid sequences and lipid species permits the investigation of a wide variety of scenarios, while the absence of explicit solvent allows for studies of large-scale phenomena.

Dynamics of coherent flow structures of a pulsating unsteady glottal jet in human phonation.

NASA Astrophysics Data System (ADS)

Neubauer, Juergen; Miraghaie, Reza; Berry, David

2004-11-01

The primary sound source for human voice is oscillation of the vocal folds in the larynx. Phonation is the self-sustained oscillation of the viscoelastic vocal fold tissue driven by the air flow from the lung. It is due to the flow-induced Hopf instability of the biomechanical-aerodynamic system of vocal folds coupled to the aeroacoustic driving air flow. The aim of this study is to provide insight to the aero-acoustic part of the primary sound source of human voice. A physical rubber model of vocal folds with air flow conditions typical for human phonation was used. This model exhibits self-sustained oscillations similar to those in human phonation. The oscillating physical model can be regarded as a dynamic slit-like orifice that discharges a pulsating unsteady jet. A left-right flapping of the glottal jet axis was detected using hotwire anemometer measurements of the unsteady glottal jet. Flow visualization experiments revealed the detachment of the glottal jet from the physical model folds during the accelerating and decelerating phase of the jet pulsation. Roll-up of large-scale vortex rings as well as secondary vortex shedding in the form of Von Karman street due to shear layer instability were found downstream of the physical model.

Free Energy Landscape - Settlements of Key Residues.

NASA Astrophysics Data System (ADS)

Aroutiounian, Svetlana

2007-03-01

FEL perspective in studies of protein folding transitions reflects notion that since there are ˜10^N conformations to scan in search of lowest free energy state, random search is beyond biological timescale. Protein folding must follow certain fel pathways and folding kinetics of evolutionary selected proteins dominates kinetic traps. Good model for functional robustness of natural proteins - coarse-grained model protein is not very accurate but affords bringing simulations closer to biological realm; Go-like potential secures the fel funnel shape; biochemical contacts signify the funnel bottleneck. Boltzmann-weighted ensemble of protein conformations and histogram method are used to obtain from MC sampling of protein conformational space the approximate probability distribution. The fel is F(rmsd) = -1/βLn[Hist(rmsd)], β=kBT and rmsd is root-mean-square-deviation from native conformation. The sperm whale myoglobin has rich dynamic behavior, is small and large - on computational scale, has a symmetry in architecture and unusual sextet of residue pairs. Main idea: there is a mathematical relation between protein fel and a key residues set providing stability to folding transition. Is the set evolutionary conserved also for functional reasons? Hypothesis: primary sequence determines the key residues positions conserved as stabilizers and the fel is the battlefield for the folding stability. Preliminary results: primary sequence - not the architecture, is the rule settler, indeed.

Molecular Dynamics based on a Generalized Born solvation model: application to protein folding

NASA Astrophysics Data System (ADS)

Onufriev, Alexey

2004-03-01

An accurate description of the aqueous environment is essential for realistic biomolecular simulations, but may become very expensive computationally. We have developed a version of the Generalized Born model suitable for describing large conformational changes in macromolecules. The model represents the solvent implicitly as continuum with the dielectric properties of water, and include charge screening effects of salt. The computational cost associated with the use of this model in Molecular Dynamics simulations is generally considerably smaller than the cost of representing water explicitly. Also, compared to traditional Molecular Dynamics simulations based on explicit water representation, conformational changes occur much faster in implicit solvation environment due to the absence of viscosity. The combined speed-up allow one to probe conformational changes that occur on much longer effective time-scales. We apply the model to folding of a 46-residue three helix bundle protein (residues 10-55 of protein A, PDB ID 1BDD). Starting from an unfolded structure at 450 K, the protein folds to the lowest energy state in 6 ns of simulation time, which takes about a day on a 16 processor SGI machine. The predicted structure differs from the native one by 2.4 A (backbone RMSD). Analysis of the structures seen on the folding pathway reveals details of the folding process unavailable form experiment.

Structural Analyses of the Kahiltna Terrane: A Kinematic Record of the Collision of the Talkeetna Superterrane

NASA Astrophysics Data System (ADS)

Bier, S. E.; Fisher, D.

2002-12-01

Macro-, meso-, and microscale structural analyses from several localities across the ~1000 km Kahiltna Terrane provide valuable kinematic insights into the late Cretaceous collision between the Talkeetna superterrane and North America. The Kahiltna Terrane, a Jurassic-Cretaceous flysch basin inboard of the Talkeetna superterrane (Wrangellia, Peninsular, and Alexander terranes), contains incremental strain indicators that record a history of oblique collision and subsequent deformation in a strike-slip regime. A comparison of structural data from localities across the Kahiltna terrane suggests a unique history not yet described in previous work on south-central Alaskan tectonics. Data was collected from the Reindeer Hills area, the northwestern Talkeetna Mountains, Denali National Park, the Peters Hills, and the Tordrillo Mountains. In the Reindeer Hills, a melange zone occurs as a series of exposures dismembered by ongoing strike slip faulting between the flysch of the Kahiltna terrane and the precollisional edge of the North American continent. This melange is characterized by fault-bounded blocks of Paleozoic limestone and sandstone within an argillite matrix with a conspicuous scaly fabric. The blocks range in size from 10 cm to tens of meters; and melange fish indicate a south-directed shear sense. The melange is overlain by a red and green (Triassic-Jurassic?) conglomerate along an unconformity that likely marks the base of a perched slope basin near the toe of an accretionary wedge. The strike of bedding and cleavage in this area trends EW. The fold axes trend NW-SE and folds verge to the south. In the northwest corner of the Talkeetna Mountains, the structure is dominated by north vergent folds and faults. The strike of bedding trends ~025°; whereas the strike of the cleavage is ~060°. Both cleavage and bedding dip to the southeast. The fold axes trend roughly NE-SW. North of the Denali Fault System, in Denali National Park, strike of bedding is ~122° and the dip is to the southwest. Folds can be divided into two sets: 1) tight folds with axes trending E-W and 2) open folds with axes that trend N-S. Cleavage is axial planar to the first set of folds. Crenulation cleavage that trends E-W may also be associated with the first set of folds. In the Peters Hills, reversals in facing direction indicate the presence of multiple macroscale folds. The strike of bedding and cleavage trend ~240° and dip to the northwest. Outcrop observations of smaller scale north-vergent folds and larger scale south-vergent folds suggest multiple deformation events. Stretching lineations trend NE-SW, and incremental strain indicators record indicate a dextral shearing event. The Kahiltna terrane exposed in the vicinity of the Tordrillo Mountains consists of alternating volcaniclastic sandstones and turbidite sequences. The strike of bedding and cleavage is ~240°, and they dip steeply to the northwest. Small isoclinal folds and faults indicate northwestward transport and deformation overprinted by large-scale open folds that verge to the east. Observations of the melange indicate precollisional northward-dipping subduction beneath an accretionary assemblage of Triassic(?) material. Structural observations from multiple localities across the Kahiltna terrane indicate northward-directed thrusting related to dextral transpression and oblique collision of the Talkeetna superterrane, with varying amounts of obliquity along the margin.

Aryl-Aryl Interactions in Designed Peptide Folds: Spectroscopic Characteristics and Placement Issues for Optimal Structure Stabilization

PubMed Central

Anderson, Jordan M.; Kier, Brandon; Jurban, Brice; Byrne, Aimee; Shu, Irene; Eidenschink, Lisa A.; Shcherbakov, Alexander A.; Hudson, Mike; Fesinmeyer, R. M.; Andersen, Niels H.

2017-01-01

We have extended our studies of Trp/Trp to other Aryl/Aryl through-space interactions that stabilize hairpins and other small polypeptide folds. Herein we detail the NMR and CD spectroscopic features of these types of interactions. NMR data remains the best diagnostic for characterizing the common T-shape orientation. Designated as an edge-to-face (EtF or FtE) interaction, large ring current shifts are produced at the edge aryl ring hydrogens and, in most cases, large exciton couplets appear in the far UV circular dichroic (CD) spectrum. The preference for the face aryl in FtE clusters is W≫Y≥F (there are some exceptions in the Y/F order); this sequence corresponds to the order of fold stability enhancement and always predicts the amplitude of the lower energy feature of the exciton couplet in the CD spectrum. The CD spectra for FtE W/W, W/Y, Y/W, and Y/Y pairs all include an intense feature at 225–232 nm. An additional couplet feature seen for W/Y, W/F, Y/Y and F/Y clusters, is a negative feature at 197–200 nm. Tyr/Tyr (as well as F/Y and F/F) interactions produce much smaller exciton couplet amplitudes. The Trp-cage fold was employed to search for the CD effects of other Trp/Trp and Trp/Tyr cluster geometries: several were identified. In this account, we provide additional examples of the application of cross-strand aryl/aryl clusters for the design of stable β-sheet models and a scale of fold stability increments associated with all possible FtE Ar/Ar clusters in several structural contexts. PMID:26850220

Effects of Vocal Fold Nodules on Glottal Cycle Measurements Derived from High-Speed Videoendoscopy in Children

PubMed Central

2016-01-01

The goal of this study is to quantify the effects of vocal fold nodules on vibratory motion in children using high-speed videoendoscopy. Differences in vibratory motion were evaluated in 20 children with vocal fold nodules (5–11 years) and 20 age and gender matched typically developing children (5–11 years) during sustained phonation at typical pitch and loudness. Normalized kinematic features of vocal fold displacements from the mid-membranous vocal fold point were extracted from the steady-state high-speed video. A total of 12 kinematic features representing spatial and temporal characteristics of vibratory motion were calculated. Average values and standard deviations (cycle-to-cycle variability) of the following kinematic features were computed: normalized peak displacement, normalized average opening velocity, normalized average closing velocity, normalized peak closing velocity, speed quotient, and open quotient. Group differences between children with and without vocal fold nodules were statistically investigated. While a moderate effect size was observed for the spatial feature of speed quotient, and the temporal feature of normalized average closing velocity in children with nodules compared to vocally normal children, none of the features were statistically significant between the groups after Bonferroni correction. The kinematic analysis of the mid-membranous vocal fold displacement revealed that children with nodules primarily differ from typically developing children in closing phase kinematics of the glottal cycle, whereas the opening phase kinematics are similar. Higher speed quotients and similar opening phase velocities suggest greater relative forces are acting on vocal fold in the closing phase. These findings suggest that future large-scale studies should focus on spatial and temporal features related to the closing phase of the glottal cycle for differentiating the kinematics of children with and without vocal fold nodules. PMID:27124157

Widespread signatures of local mRNA folding structure selection in four Dengue virus serotypes

PubMed Central

2015-01-01

Background It is known that mRNA folding can affect and regulate various gene expression steps both in living organisms and in viruses. Previous studies have recognized functional RNA structures in the genome of the Dengue virus. However, these studies usually focused either on the viral untranslated regions or on very specific and limited regions at the beginning of the coding sequences, in a limited number of strains, and without considering evolutionary selection. Results Here we performed the first large scale comprehensive genomics analysis of selection for local mRNA folding strength in the Dengue virus coding sequences, based on a total of 1,670 genomes and 4 serotypes. Our analysis identified clusters of positions along the coding regions that may undergo a conserved evolutionary selection for strong or weak local folding maintained across different viral variants. Specifically, 53-66 clusters for strong folding and 49-73 clusters for weak folding (depending on serotype) aggregated of positions with a significant conservation of folding energy signals (related to partially overlapping local genomic regions) were recognized. In addition, up to 7% of these positions were found to be conserved in more than 90% of the viral genomes. Although some of the identified positions undergo frequent synonymous / non-synonymous substitutions, the selection for folding strength therein is preserved, and thus cannot be trivially explained based on sequence conservation alone. Conclusions The fact that many of the positions with significant folding related signals are conserved among different Dengue variants suggests that a better understanding of the mRNA structures in the corresponding regions may promote the development of prospective anti- Dengue vaccination strategies. The comparative genomics approach described here can be employed in the future for detecting functional regions in other pathogens with very high mutations rates. PMID:26449467

Going beyond Clustering in MD Trajectory Analysis: An Application to Villin Headpiece Folding

PubMed Central

Rajan, Aruna; Freddolino, Peter L.; Schulten, Klaus

2010-01-01

Recent advances in computing technology have enabled microsecond long all-atom molecular dynamics (MD) simulations of biological systems. Methods that can distill the salient features of such large trajectories are now urgently needed. Conventional clustering methods used to analyze MD trajectories suffer from various setbacks, namely (i) they are not data driven, (ii) they are unstable to noise and changes in cut-off parameters such as cluster radius and cluster number, and (iii) they do not reduce the dimensionality of the trajectories, and hence are unsuitable for finding collective coordinates. We advocate the application of principal component analysis (PCA) and a non-metric multidimensional scaling (nMDS) method to reduce MD trajectories and overcome the drawbacks of clustering. To illustrate the superiority of nMDS over other methods in reducing data and reproducing salient features, we analyze three complete villin headpiece folding trajectories. Our analysis suggests that the folding process of the villin headpiece is structurally heterogeneous. PMID:20419160

Going beyond clustering in MD trajectory analysis: an application to villin headpiece folding.

PubMed

Rajan, Aruna; Freddolino, Peter L; Schulten, Klaus

2010-04-15

Recent advances in computing technology have enabled microsecond long all-atom molecular dynamics (MD) simulations of biological systems. Methods that can distill the salient features of such large trajectories are now urgently needed. Conventional clustering methods used to analyze MD trajectories suffer from various setbacks, namely (i) they are not data driven, (ii) they are unstable to noise and changes in cut-off parameters such as cluster radius and cluster number, and (iii) they do not reduce the dimensionality of the trajectories, and hence are unsuitable for finding collective coordinates. We advocate the application of principal component analysis (PCA) and a non-metric multidimensional scaling (nMDS) method to reduce MD trajectories and overcome the drawbacks of clustering. To illustrate the superiority of nMDS over other methods in reducing data and reproducing salient features, we analyze three complete villin headpiece folding trajectories. Our analysis suggests that the folding process of the villin headpiece is structurally heterogeneous.

Estimation of fine-scale recombination intensity variation in the white-echinus interval of D. melanogaster

PubMed Central

Singh, Nadia D.; Aquadro, Charles F.; Clark, Andrew G.

2009-01-01

Accurate assessment of local recombination rate variation is crucial for understanding the recombination process and for determining the impact of natural selection on linked sites. In Drosophila, local recombination intensity has been estimated primarily by statistical approaches, estimating the local slope of the relationship between the physical and genetic maps. However, these estimates are limited in resolution, and as a result, the physical scale at which recombination intensity varies in Drosophila is largely unknown. While there is some evidence suggesting as much as a 40-fold variation in crossover rate at a local scale in D. pseudoobscura, little is known about the fine-scale structure of recombination rate variation in D. melanogaster. Here, we experimentally examine the fine-scale distribution of crossover events in a 1.2 Mb region on the D. melanogaster X chromosome using a classic genetic mapping approach. Our results show that crossover frequency is significantly heterogeneous within this region, varying ~ 3.5 fold. Simulations suggest that this degree of heterogeneity is sufficient to affect levels of standing nucleotide diversity, although the magnitude of this effect is small. We recover no statistical association between empirical estimates of nucleotide diversity and recombination intensity, which is likely due to the limited number of loci sampled in our population genetic dataset. However, codon bias is significantly negatively correlated with fine-scale recombination intensity estimates, as expected. Our results shed light on the relevant physical scale to consider in evolutionary analyses relating to recombination rate, and highlight the motivations to increase the resolution of the recombination map in Drosophila. PMID:19504037

Efficient preconditioning of the electronic structure problem in large scale ab initio molecular dynamics simulations

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

Schiffmann, Florian; VandeVondele, Joost, E-mail: Joost.VandeVondele@mat.ethz.ch

2015-06-28

We present an improved preconditioning scheme for electronic structure calculations based on the orbital transformation method. First, a preconditioner is developed which includes information from the full Kohn-Sham matrix but avoids computationally demanding diagonalisation steps in its construction. This reduces the computational cost of its construction, eliminating a bottleneck in large scale simulations, while maintaining rapid convergence. In addition, a modified form of Hotelling’s iterative inversion is introduced to replace the exact inversion of the preconditioner matrix. This method is highly effective during molecular dynamics (MD), as the solution obtained in earlier MD steps is a suitable initial guess. Filteringmore » small elements during sparse matrix multiplication leads to linear scaling inversion, while retaining robustness, already for relatively small systems. For system sizes ranging from a few hundred to a few thousand atoms, which are typical for many practical applications, the improvements to the algorithm lead to a 2-5 fold speedup per MD step.« less

Spatio-temporal hierarchy in the dynamics of a minimalist protein model

NASA Astrophysics Data System (ADS)

Matsunaga, Yasuhiro; Baba, Akinori; Li, Chun-Biu; Straub, John E.; Toda, Mikito; Komatsuzaki, Tamiki; Berry, R. Stephen

2013-12-01

A method for time series analysis of molecular dynamics simulation of a protein is presented. In this approach, wavelet analysis and principal component analysis are combined to decompose the spatio-temporal protein dynamics into contributions from a hierarchy of different time and space scales. Unlike the conventional Fourier-based approaches, the time-localized wavelet basis captures the vibrational energy transfers among the collective motions of proteins. As an illustrative vehicle, we have applied our method to a coarse-grained minimalist protein model. During the folding and unfolding transitions of the protein, vibrational energy transfers between the fast and slow time scales were observed among the large-amplitude collective coordinates while the other small-amplitude motions are regarded as thermal noise. Analysis employing a Gaussian-based measure revealed that the time scales of the energy redistribution in the subspace spanned by such large-amplitude collective coordinates are slow compared to the other small-amplitude coordinates. Future prospects of the method are discussed in detail.

Spatial confinement of active microtubule networks induces large-scale rotational cytoplasmic flow

PubMed Central

Suzuki, Kazuya; Miyazaki, Makito; Takagi, Jun; Itabashi, Takeshi; Ishiwata, Shin’ichi

2017-01-01

Collective behaviors of motile units through hydrodynamic interactions induce directed fluid flow on a larger length scale than individual units. In cells, active cytoskeletal systems composed of polar filaments and molecular motors drive fluid flow, a process known as cytoplasmic streaming. The motor-driven elongation of microtubule bundles generates turbulent-like flow in purified systems; however, it remains unclear whether and how microtubule bundles induce large-scale directed flow like the cytoplasmic streaming observed in cells. Here, we adopted Xenopus egg extracts as a model system of the cytoplasm and found that microtubule bundle elongation induces directed flow for which the length scale and timescale depend on the existence of geometrical constraints. At the lower activity of dynein, kinesins bundle and slide microtubules, organizing extensile microtubule bundles. In bulk extracts, the extensile bundles connected with each other and formed a random network, and vortex flows with a length scale comparable to the bundle length continually emerged and persisted for 1 min at multiple places. When the extracts were encapsulated in droplets, the extensile bundles pushed the droplet boundary. This pushing force initiated symmetry breaking of the randomly oriented bundle network, leading to bundles aligning into a rotating vortex structure. This vortex induced rotational cytoplasmic flows on the length scale and timescale that were 10- to 100-fold longer than the vortex flows emerging in bulk extracts. Our results suggest that microtubule systems use not only hydrodynamic interactions but also mechanical interactions to induce large-scale temporally stable cytoplasmic flow. PMID:28265076

Biopsy using a magnetic capsule endoscope carrying, releasing, and retrieving untethered microgrippers.

PubMed

Yim, Sehyuk; Gultepe, Evin; Gracias, David H; Sitti, Metin

2014-02-01

This paper proposes a new wireless biopsy method where a magnetically actuated untethered soft capsule endoscope carries and releases a large number of thermo-sensitive, untethered microgrippers (μ-grippers) at a desired location inside the stomach and retrieves them after they self-fold and grab tissue samples. We describe the working principles and analytical models for the μ-gripper release and retrieval mechanisms, and evaluate the proposed biopsy method in ex vivo experiments. This hierarchical approach combining the advanced navigation skills of centimeter-scaled untethered magnetic capsule endoscopes with highly parallel, autonomous, submillimeter scale tissue sampling μ-grippers offers a multifunctional strategy for gastrointestinal capsule biopsy.

paraGSEA: a scalable approach for large-scale gene expression profiling

PubMed Central

Peng, Shaoliang; Yang, Shunyun

2017-01-01

Abstract More studies have been conducted using gene expression similarity to identify functional connections among genes, diseases and drugs. Gene Set Enrichment Analysis (GSEA) is a powerful analytical method for interpreting gene expression data. However, due to its enormous computational overhead in the estimation of significance level step and multiple hypothesis testing step, the computation scalability and efficiency are poor on large-scale datasets. We proposed paraGSEA for efficient large-scale transcriptome data analysis. By optimization, the overall time complexity of paraGSEA is reduced from O(mn) to O(m+n), where m is the length of the gene sets and n is the length of the gene expression profiles, which contributes more than 100-fold increase in performance compared with other popular GSEA implementations such as GSEA-P, SAM-GS and GSEA2. By further parallelization, a near-linear speed-up is gained on both workstations and clusters in an efficient manner with high scalability and performance on large-scale datasets. The analysis time of whole LINCS phase I dataset (GSE92742) was reduced to nearly half hour on a 1000 node cluster on Tianhe-2, or within 120 hours on a 96-core workstation. The source code of paraGSEA is licensed under the GPLv3 and available at http://github.com/ysycloud/paraGSEA. PMID:28973463

A Simple and Effective Protein Folding Activity Suitable for Large Lectures

ERIC Educational Resources Information Center

White, Brian

2006-01-01

This article describes a simple and inexpensive hands-on simulation of protein folding suitable for use in large lecture classes. This activity uses a minimum of parts, tools, and skill to simulate some of the fundamental principles of protein folding. The major concepts targeted are that proteins begin as linear polypeptides and fold to…

Tectono-sedimentary evolution of salt controlled minibasin in a fold-an-thrust belt setting Example from the Sivas Basin Turkey and physical model.

NASA Astrophysics Data System (ADS)

Kergaravat, Charlie; Ribes, Charlotte; Darnault, Romain; Callot, Jean-Paul; Ringenbach, Jean-Claude

2017-04-01

The aim of this study is to present the influence of regional shortening on the evolution of a minibasin province and the associated foldbelt geometry based on a natural example, the Sivas Basin, then compared to a physical experiment. The Sivas Basin in the Central Anatolian Plateau (Turkey) is a foreland fold-and-thrust belt, displaying in the central part a typical wall and basin province characterized by spectacularly exposed minibasins, separated by continuous steep-flanked walls and diapirs over a large area (45x25 km). The advance of the orogenic wedge is expressed within the second generation of minibasins by a shortening-induced squeezing of diapirs. Network of walls and diapirs evolve form polygonal to linear pattern probably induced by the squeezing of pre-existing evaporite walls and diapirs, separating linear primary minibasins. From base to top of secondary minibasins, halokinetic structures seem to evolve from small-scale objects along diapir flanks, showing hook and wedges halokinetic sequences, to large stratigraphic wedging, megaflap and salt sheets. Minibasins show progressively more linear shape at right angle to the regional shortening and present angular unconformities along salt structures related to the rejuvenation of pre-existing salt diapirs and walls probably encouraged by the shortening tectonic regime. The advance of the fold-and-thrust belts during the minibasins emplacement is mainly expressed during the late stage of minibasins development by a complex polygonal network of small- and intermediate-scale tectonic objects: (1) squeezed evaporite walls and diapirs, sometimes thrusted forming oblique or vertical welds, (2) allochthonous evaporite sheets, (3) thrusts and strike-slip faults recording translation and rotation of minibasins about vertical axis. Some minibasins are also tilted, with up to vertical position, associated with both the salt expulsion during minibasins sinking, recorded by large stratigraphic wedge, and the late thrust faults developments. The influence of the regional shortening deformation seems to be effective when the majority of the evaporite is remobilized toward the foreland. Results of scaled physical experiments, where continuous shortening is applied during minibasins emplacement, closely match with the deformation patterns observed in the Sivas minibasins. Shortening induce deformations such as translation of minibasins basinward, strike-slip fault zones along minibasin margin, rejuvenation of silicon walls and diapirs, emergence of silicon glaciers and rotation of minibasins along vertical and horizontal axis.

Large-scale purification and biochemical characterization of crystallization-grade porin protein P from Pseudomonas aeruginosa.

PubMed

Worobec, E A; Martin, N L; McCubbin, W D; Kay, C M; Brayer, G D; Hancock, R E

1988-04-07

A large-scale purification scheme was developed for lipopolysaccharide-free protein P, the phosphate-starvation-inducible outer-membrane porin from Pseudomonas aeruginosa. This highly purified protein P was used to successfully form hexagonal crystals in the presence of n-octyl-beta-glucopyranoside. Amino-acid analysis indicated that protein P had a similar composition to other bacterial outer membrane proteins, containing a high percentage (50%) of hydrophilic residues. The amino-terminal sequence of this protein, although not homologous to either outer membrane protein, PhoE or OmpF, of Escherichia coli, was found to have an analogous protein-folding pattern. Protein P in the native trimer form was capable of maintaining a stable functional trimer after proteinase cleavage. This suggested the existence of a strongly associated tertiary and quaternary structure. Circular dichroism studies confirmed these results in that a large proportion of the protein structure was determined to be beta-sheet and resistant to acid pH and heating in 0.1% sodium dodecyl sulphate.

Accelerating large-scale simulation of seismic wave propagation by multi-GPUs and three-dimensional domain decomposition

NASA Astrophysics Data System (ADS)

Okamoto, Taro; Takenaka, Hiroshi; Nakamura, Takeshi; Aoki, Takayuki

2010-12-01

We adopted the GPU (graphics processing unit) to accelerate the large-scale finite-difference simulation of seismic wave propagation. The simulation can benefit from the high-memory bandwidth of GPU because it is a "memory intensive" problem. In a single-GPU case we achieved a performance of about 56 GFlops, which was about 45-fold faster than that achieved by a single core of the host central processing unit (CPU). We confirmed that the optimized use of fast shared memory and registers were essential for performance. In the multi-GPU case with three-dimensional domain decomposition, the non-contiguous memory alignment in the ghost zones was found to impose quite long time in data transfer between GPU and the host node. This problem was solved by using contiguous memory buffers for ghost zones. We achieved a performance of about 2.2 TFlops by using 120 GPUs and 330 GB of total memory: nearly (or more than) 2200 cores of host CPUs would be required to achieve the same performance. The weak scaling was nearly proportional to the number of GPUs. We therefore conclude that GPU computing for large-scale simulation of seismic wave propagation is a promising approach as a faster simulation is possible with reduced computational resources compared to CPUs.

3D Visualization of Sheath Folds in Roman Marble from Ephesus, Turkey

NASA Astrophysics Data System (ADS)

Wex, Sebastian; Passchier, Cornelis W.; de Kemp, Eric A.; Ilhan, Sinan

2013-04-01

Excavation of a palatial 2nd century AD house (Terrace House Two) in the ancient city of Ephesus, Turkey in the 1970s produced 10.313 pieces of colored, folded marble which belonged to 54 marble plates of 1.6 cm thickness that originally covered the walls of the banquet hall of the house. The marble plates were completely reassembled and restored by a team of workers over the last 6 years. The plates were recognized as having been sawn from two separate large blocks of "Cipollino verde", a green mylonitized marble from Karystos on the Island of Euboea, Greece. After restoration, it became clear that all slabs had been placed on the wall in approximately the sequence in which they had been cut off by a Roman stone saw. As a result, the marble plates give a full 3D insight in the folded internal structure of 1m3 block of mylonite. The restoration of the slabs was recognized as a first, unique opportunity for detailed reconstruction of the 3D geometry of m-scale folds in mylonitized marble. Photographs were taken of each slab and used to reconstruct their exact arrangement within the originally quarried blocks. Outlines of layers were digitized and a full 3D reconstruction of the internal structure of the block was created using ArcMap and GOCAD. Fold structures in the block include curtain folds and multilayered sheath folds. Several different layers showing these structures were digitized on the photographs of the slab surfaces and virtually mounted back together within the model of the marble block. Due to the serial sectioning into slabs, with cm-scale spacing, the visualization of the 3D geometry of sheath folds was accomplished with a resolution better than 4 cm. Final assembled 3D images reveal how sheath folds emerge from continuous layers and show their overall consistency as well as a constant hinge line orientation of the fold structures. Observations suggest that a single deformation phase was responsible for the evolution of "Cipollino verde" structures. Furthermore the XY plane of all analyzed sheath folds was orientated perpendicular to the layering of the marble, indicating a compressional component during shear deformation. This study sheds light on the general evolution and possible interpretation of sheath folds, currently still subject of debate, and on the structural evolution of "Cipollino verde", which is still used in modern architectural design. Furthermore, the detailed analysis of the slabs helps in the interpretation and reconstruction of Roman stone saws. For future applications this work could serve as an excellent 3D test set for geologic reconstruction methodologies and interpolation algorithms. The results presented could only be obtained by close cooperation of workers in geology and archaeology.

Miocene to present deformation rates in the Yakima Fold Province and implications for earthquake hazards in central Washington State, USA

NASA Astrophysics Data System (ADS)

Staisch, Lydia; Sherrod, Brian; Kelsey, Harvey; Blakely, Richard; Möller, Andreas; Styron, Richard

2017-04-01

The Yakima fold province (YFP), located in the Cascadia backarc of central Washington, is a region of active distributed deformation that accommodates NNE-SSW shortening. Geodetic data show modern strain accumulation of 2 mm/yr across this large-scale fold province. Deformation rates on individual structures, however, are difficult to assess from GPS data given low strain rates and the relatively short time period of geodetic observation. Geomorphic and geologic records, on the other hand, span sufficient time to investigate deformation rates on the folds. Resolving fault geometries and slip rates of the YFP is imperative to seismic hazard assessment for nearby infrastructure, including a large nuclear waste facility and hydroelectric dams along the Columbia and Yakima Rivers. We present new results on the timing and magnitude of deformation across several Yakima folds, including the Manastash Ridge, Umtanum Ridge, and Saddle Mountains anticlines. We constructed several line-balanced cross sections across the folds to calculated the magnitude of total shortening since Miocene time. To further constrain our structural models, we include forward-modeling of magnetic and gravity anomaly data. We estimate total shortening between 1.0 and 2.4 km across individual folds, decreasing eastward, consistent with geodetically and geologically measured clockwise rotation. Importantly, we find that thrust faults reactivate and invert normal faults in the basement, and do not appear to sole into a common décollement at shallow to mid-crustal depth. We constrain spatial and temporal variability in deformation rates along the Saddle Mountains, Manastash Ridge and Umtanum Ridge anticlines using geomorphic and stratigraphic markers of topographic evolution. From stratigraphy and geochronology of growth strata along the Saddle Mountains we find that the rate of deformation has increased up to six-fold since late Miocene time. To constrain deformation rates along other Yakima folds, which lack syntectonic growth strata, we exploit 2-m LiDAR data and invert stream profiles to analytically solve for a linear solution to relative uplift rate. From stream profile inversion, we see an increase in incision rates in Pliocene time and suggest that this increased rate is tectonically controlled. Our analyses indicate that deformation rates along the Manastash and Umtanum Ridge anticlines are significantly higher than along the Saddle Mountains. We use our new estimates of slip rates along individual anticlines to calculate the time required to accumulate enough strain energy for a large magnitude earthquake (M≥7) along faults within the YFP. Our results indicate that it takes between several hundred to several thousand years to accumulate sufficient strain energy for a M≥7 earthquake, with the greatest hazard posed by the Umtanum Ridge anticline.

The Next Frontier in Computing

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

Sarrao, John

2016-11-16

Exascale computing refers to computing systems capable of at least one exaflop or a billion calculations per second (1018). That is 50 times faster than the most powerful supercomputers being used today and represents a thousand-fold increase over the first petascale computer that came into operation in 2008. How we use these large-scale simulation resources is the key to solving some of today’s most pressing problems, including clean energy production, nuclear reactor lifetime extension and nuclear stockpile aging.

An Andean-type retro-arc foreland system beneath northwest South China revealed by SINOPROBE profiling

NASA Astrophysics Data System (ADS)

Li, Jianhua; Dong, Shuwen; Cawood, Peter A.; Zhao, Guochun; Johnston, Stephen T.; Zhang, Yueqiao; Xin, Yujia

2018-05-01

In the Mesozoic, South China was situated along the convergent margin between the Asian and Pacific plates, providing an excellent laboratory to understand the interactions between deformation, sedimentation and magmatism in a retroarc environment. The crustal architecture of northwest South China is displayed along the ∼600-km-long SINOPROBE deep seismic reflection profiles and reveals from east to west: (1) highly folded and truncated reflectors in the upper crust of the Yangtze Fold Zone, which correspond to thin- and thick-skinned thrust systems, and document large-scale intraplate structural imbrication and shortening; (2) a crustal-scale flat-ramp-flat structure, termed the Main Yangtze decollement, which forms a weak, viscous layer to accommodate strain decoupling and material transport in the thin- and thick-skinned systems; and (3) nearly flat-lying reflectors in the Sichuan Basin, which support interpretation of the basin as a weakly deformed depocentre. The Yangtze Fold Zone and the Sichuan Basin represent a retro-arc foreland basin system that is >800 km away from the continental-margin magmatic arc. We suggest that tectonic processes across the arc and retro-arc systems, including arc magma flare-up, basin sedimentation, retroarc thrust propagation, lithosphere underthrusting, root foundering, and extension-related magmatism were interrelated and governed mass transfer. Age data and geological relations link the tectonic processes to evolving geodynamics of the subducting Paleo-Pacific plate.

Methodological uncertainty in quantitative prediction of human hepatic clearance from in vitro experimental systems.

PubMed

Hallifax, D; Houston, J B

2009-03-01

Mechanistic prediction of unbound drug clearance from human hepatic microsomes and hepatocytes correlates with in vivo clearance but is both systematically low (10 - 20 % of in vivo clearance) and highly variable, based on detailed assessments of published studies. Metabolic capacity (Vmax) of commercially available human hepatic microsomes and cryopreserved hepatocytes is log-normally distributed within wide (30 - 150-fold) ranges; Km is also log-normally distributed and effectively independent of Vmax, implying considerable variability in intrinsic clearance. Despite wide overlap, average capacity is 2 - 20-fold (dependent on P450 enzyme) greater in microsomes than hepatocytes, when both are normalised (scaled to whole liver). The in vitro ranges contrast with relatively narrow ranges of clearance among clinical studies. The high in vitro variation probably reflects unresolved phenotypical variability among liver donors and practicalities in processing of human liver into in vitro systems. A significant contribution from the latter is supported by evidence of low reproducibility (several fold) of activity in cryopreserved hepatocytes and microsomes prepared from the same cells, between separate occasions of thawing of cells from the same liver. The large uncertainty which exists in human hepatic in vitro systems appears to dominate the overall uncertainty of in vitro-in vivo extrapolation, including uncertainties within scaling, modelling and drug dependent effects. As such, any notion of quantitative prediction of clearance appears severely challenged.

Eyeglass: A Very Large Aperture Diffractive Space Telescope

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

Hyde, R; Dixit, S; Weisberg, A

2002-07-29

Eyeglass is a very large aperture (25-100 meter) space telescope consisting of two distinct spacecraft, separated in space by several kilometers. A diffractive lens provides the telescope's large aperture, and a separate, much smaller, space telescope serves as its mobile eyepiece. Use of a transmissive diffractive lens solves two basic problems associated with very large aperture space telescopes; it is inherently fieldable (lightweight and flat, hence packagable and deployable) and virtually eliminates the traditional, very tight, surface shape tolerances faced by reflecting apertures. The potential drawback to use of a diffractive primary (very narrow spectral bandwidth) is eliminated by correctivemore » optics in the telescope's eyepiece. The Eyeglass can provide diffraction-limited imaging with either single-band, multiband, or continuous spectral coverage. Broadband diffractive telescopes have been built at LLNL and have demonstrated diffraction-limited performance over a 40% spectral bandwidth (0.48-0.72 {micro}m). As one approach to package a large aperture for launch, a foldable lens has been built and demonstrated. A 75 cm aperture diffractive lens was constructed from 6 panels of 1 m thick silica; it achieved diffraction-limited performance both before and after folding. This multiple panel, folding lens, approach is currently being scaled-up at LLNL. We are building a 5 meter aperture foldable lens, involving 72 panels of 700 {micro}m thick glass sheets, diffractively patterned to operate as coherent f/50 lens.« less

Large-scale glacitectonic deformation in response to active ice sheet retreat across Dogger Bank (southern central North Sea) during the Last Glacial Maximum

NASA Astrophysics Data System (ADS)

Phillips, Emrys; Cotterill, Carol; Johnson, Kirstin; Crombie, Kirstin; James, Leo; Carr, Simon; Ruiter, Astrid

2018-01-01

High resolution seismic data from the Dogger Bank in the central southern North Sea has revealed that the Dogger Bank Formation records a complex history of sedimentation and penecontemporaneous, large-scale, ice-marginal to proglacial glacitectonic deformation. These processes led to the development of a large thrust-block moraine complex which is buried beneath a thin sequence of Holocene sediments. This buried glacitectonic landsystem comprises a series of elongate, arcuate moraine ridges (200 m up to > 15 km across; over 40-50 km long) separated by low-lying ice marginal to proglacial sedimentary basins and/or meltwater channels, preserving the shape of the margin of this former ice sheet. The moraines are composed of highly deformed (folded and thrust) Dogger Bank Formation with the lower boundary of the deformed sequence (up to 40-50 m thick) being marked by a laterally extensive décollement. The ice-distal parts of the thrust moraine complex are interpreted as a "forward" propagating imbricate thrust stack developed in response to S/SE-directed ice-push. The more complex folding and thrusting within the more ice-proximal parts of the thrust-block moraines record the accretion of thrust slices of highly deformed sediment as the ice repeatedly reoccupied this ice marginal position. Consequently, the internal structure of the Dogger Bank thrust-moraine complexes can be directly related to ice sheet dynamics, recording the former positions of a highly dynamic, oscillating Weichselian ice sheet margin as it retreated northwards at the end of the Last Glacial Maximum.

Evidence of Variscan and Alpine tectonics in the structural and thermochronological record of the central Serbo-Macedonian Massif (south-eastern Serbia)

NASA Astrophysics Data System (ADS)

Antić, Milorad D.; Kounov, Alexandre; Trivić, Branislav; Spikings, Richard; Wetzel, Andreas

2017-07-01

The Serbo-Macedonian Massif (SMM) represents a composite crystalline belt within the Eastern European Alpine orogen, outcropping from the Pannonian basin in the north to the Aegean Sea in the south. The central parts of this massif (south-eastern Serbia) consist of the medium- to high-grade Lower Complex and the low-grade Vlasina Unit. Outcrop- and micro-scale ductile structures in this area document three major stages of ductile deformation. The earliest stage D1 is related to isoclinal folding, commonly preserved as up to decimetre-scale quartz-feldspar rootless fold hinges. D2 is associated with general south-eastward tectonic transport and refolding of earlier structures into recumbent metre- to kilometre-scale tight to isoclinal folds. Stages D1 and D2 could not be temporally separated and probably took place in close sequence. The age of these two ductile deformation stages was constrained to the Variscan orogeny based on indirect geological evidence (i.e. ca. 408-ca. 328). During this period, the SMM was involved in a transpressional amalgamation of the western and eastern parts of the Galatian super-terrane and subsequent collision with Laurussia. Outcrop-scale evidence of the final stage D3 is limited to spaced and crenulation cleavage, which are probably related to formation of large-scale open upright folds as reported previously. 40Ar/39Ar thermochronology was applied on hornblende, muscovite, and biotite samples in order to constrain the age of tectonothermal events and activity along major shear zones. These 40Ar/39Ar data reveal three major cooling episodes affecting the central SMM. Cooling below greenschist facies conditions in the western part of the Vlasina Unit took place in a post-orogenic setting (extensional or transtensional) in the early Permian (284 ± 1 Ma). The age of activity along the top-to-the-west shear zone formed within the orthogneiss in the Božica area of the Vlasina Unit was constrained to Middle Triassic (246 ± 1 Ma). This age coincides with widespread extension related to the opening of the Mesozoic Tethys. The greenschist facies retrogression in the Lower Complex probably occurred in the Early Jurassic (195 ± 1 Ma), and it was related to the thermal processes in the overriding plate above the subducting slab of the Mesozoic Tethys Ocean.

Shortening accommodated by extension-parallel folding of detachment faults during oblique rifting in the Gulf of California

NASA Astrophysics Data System (ADS)

Seiler, Christian; Fletcher, John

2013-04-01

Large-scale fault corrugations or megamullions are a common feature of detachment faults and form either as original fault grooves, displacement-gradient folds or constrictional folds parallel to the extension direction. In highly oblique extensional settings such as the Gulf of California, horizontal shortening perpendicular to the extension direction is an inherent part of the regional stress field and likely forms a key factor during the development of extension-parallel fault corrugations. However, the amount of horizontal shortening absorbed by megamullions is difficult to quantify, and constrictional folding is not normally thought to accommodate significant strike-slip deformation. The Las Cuevitas and Santa Rosa detachments are two low-angle normal fault systems exposed on the Gulf of California rifted margin in northeastern Baja California, Mexico. The two detachments accommodate between ~7-9km of SE-directed extension and represent the next significant set of faults in direction of transport from the rift breakaway fault. Fault kinematics are highly complex, but suggest integrated normal, oblique- and strike-slip faulting, with kinematics controlled by the orientation of faults with respect to the regional transtensional stress field. Both fault systems are strongly corrugated, with megamullion amplitudes of ~4-7km and half wavelenghts of between ~15 to 20km. Differential folding of the syntectonic basin-fill of the supradetachment basins strongly suggest that the observed megamullions formed largely, though not exclusively, due to constrictional folding associated with the transtensional stress regime of the plate boundary. This is consistent with basin-scale facies variations that record differential uplift and subsidence in antiformal and synformal megamullion domains, respectively. Compared to the two detachments, the San Pedro Martir fault - the master fault of the rift system at this latitude - shows more subtle fault corrugations with amplitudes of <3km. Unlike the Las Cuevitas and Santa Rosa detachments, though, there is no evidence for constrictional folding on the San Pedro Martir fault. Instead, the observed corrugations likely represent original grooves of the fault plane, formed as adjacent fault nuclei joined along-strike during fault growth. Comparison between the sinuosity of the San Pedro Martir fault (1.08), attributed entirely to original fault asperities, with the sinuosity of the two detachment systems (Las Cuevitas detachment: 1.17, Santa Rosa detachment: 1.22), suggests that about 10% of shortening occurred on each of the two detachments due to synextensional constrictional folding. This corresponds to a combined total of ~8km of N-S shortening, or ~10km of dextral shear resolved in direction of the relative plate motion, and occurs in addition to ~21km of right-lateral strain accommodated by clockwise vertical-axis block rotations. Thus, strain in this part of the rift system was partitioned between discrete extensional faulting on the two detachment systems, and significant right-lateral shear accommodated by distributed volume deformation.

Interference of lithospheric folding in Central Asia by simultaneous Indian and Arabian plate indentation

NASA Astrophysics Data System (ADS)

Smit, J. H. W.; Cloetingh, S. A. P. L.; Burov, E.; Sokoutis, D.; Kaban, M.; Tesauro, M.; Burg, J.-P.

2012-04-01

Although large-scale folding of the crust and the lithosphere in Central Asia as a result of the indentation of India has been extensively documented, the impact of continental collision between Arabia and Eurasia has been largely overlooked. The resulting Neogene shortening and uplift of the Zagros, Albors, Kopet Dagh and Kaukasus mountain belts in Iran and surrounding areas is characterised by a simultaneous onset of major topography growth at ca. 5 Ma. At the same time, the adjacent Caspian, Turan and Amu Darya basins underwent an acceleration in subsidence. It is common knowledge that waves with different orientations will interfere with each other. Folding, by its nature similar to a standing wave, is not likely to be an exception. We demonstrate that collision of the Eurasian plate with the Arabian and Indian plates generates folding of the Eurasian lithosphere in two different directions and that interaction between both generates characteristic interference patterns that can be recognised from the regional gravity signal. We present evidence for interference of lithospheric folding patterns induced by Arabian and Indian collision with Eurasia. Wavelengths (from 50 to 250 km) and spatial patterns are inferred from satellite-derived topography and gravity models and attest for rheologically stratified lithosphere with relatively strong mantle rheology (thickness of strong mechanical core on the order of 40-50 km) and less competent crust (thickness of the mechanical core on the order of 10-15 km). The observations are compared with inferences from numerical and analogue tectonic experiments for a quantitative assessment of factors such as lithosphere rheology and stratification, lateral variations in lithosphere strength, thermo-mechanical age and distance to the plate boundary on the activity of folding as a mechanism of intra-plate deformation in this area. The observed interference of the patterns of folding appears to be primarily the result of spatial orientation of the two indenters, differences in their convergence velocities and the thermo-mechanical structure of the lithosphere west and east of the Kugitang-Tunka line.

Theoretical Insights into the Biophysics of Protein Bi-stability and Evolutionary Switches

PubMed Central

Krobath, Heinrich; Chan, Hue Sun

2016-01-01

Deciphering the effects of nonsynonymous mutations on protein structure is central to many areas of biomedical research and is of fundamental importance to the study of molecular evolution. Much of the investigation of protein evolution has focused on mutations that leave a protein’s folded structure essentially unchanged. However, to evolve novel folds of proteins, mutations that lead to large conformational modifications have to be involved. Unraveling the basic biophysics of such mutations is a challenge to theory, especially when only one or two amino acid substitutions cause a large-scale conformational switch. Among the few such mutational switches identified experimentally, the one between the GA all-α and GB α+β folds is extensively characterized; but all-atom simulations using fully transferrable potentials have not been able to account for this striking switching behavior. Here we introduce an explicit-chain model that combines structure-based native biases for multiple alternative structures with a general physical atomic force field, and apply this construct to twelve mutants spanning the sequence variation between GA and GB. In agreement with experiment, we observe conformational switching from GA to GB upon a single L45Y substitution in the GA98 mutant. In line with the latent evolutionary potential concept, our model shows a gradual sequence-dependent change in fold preference in the mutants before this switch. Our analysis also indicates that a sharp GA/GB switch may arise from the orientation dependence of aromatic π-interactions. These findings provide physical insights toward rationalizing, predicting and designing evolutionary conformational switches. PMID:27253392

Experimental study of air delivery into water-conveyance system of the radial-axial turbine

NASA Astrophysics Data System (ADS)

Maslennikova, Alexandra; Platonov, Dmitry; Minakov, Andrey; Dekterev, Dmitry

2017-10-01

The paper presents an experimental study of oscillatory response in the Francis turbine of hydraulic unit. The experiment was performed on large-scale hydrodynamic test-bench with impeller diameter of 0.3 m. The effect of air injection on the intensity of pressure pulsations was studied at the maximum pressure pulsations in the hydraulic unit. It was revealed that air delivery into the water-conveyance system of the turbine results in almost two-fold reduction of pressure pulsations.

The Next Frontier in Computing

ScienceCinema

Sarrao, John

2018-06-13

Exascale computing refers to computing systems capable of at least one exaflop or a billion calculations per second (1018). That is 50 times faster than the most powerful supercomputers being used today and represents a thousand-fold increase over the first petascale computer that came into operation in 2008. How we use these large-scale simulation resources is the key to solving some of today’s most pressing problems, including clean energy production, nuclear reactor lifetime extension and nuclear stockpile aging.

The review on tessellation origami inspired folded structure

NASA Astrophysics Data System (ADS)

Chu, Chai Chen; Keong, Choong Kok

2017-10-01

Existence of folds enhances the load carrying capacity of a folded structure which makes it suitable to be used for application where large open space is required such as large span roof structures and façade. Folded structure is closely related to origami especially the tessellation origami. Tessellation origami provides a folded configuration with facetted surface as a result from repeated folding pattern. Besides that, tessellation origami has flexible folding mechanism that produced a variety of 3-dimensional folded configurations. Despite the direct relationship between fold in origami and folded structure, the idea of origami inspired folded structure is not properly reviewed in the relevant engineering field. Hence, this paper aims to present the current studies from related discipline which has direct relation with application of tessellation origami in folded structure. First, tessellation origami is properly introduced and defined. Then, the review covers the topic on the origami tessellation design suitable for folded structure, its modeling and simulation method, and existing studies and applications of origami as folded structure is presented. The paper also includes the discussion on the current issues related to each topic.

Analysis of folded pulse forming line operation.

PubMed

Domonkos, M T; Watrous, J; Parker, J V; Cavazos, T; Slenes, K; Heidger, S; Brown, D; Wilson, D

2014-09-01

A compact pulse forming line (CPFL) concept based on a folded transmission line and high-breakdown strength dielectric was explored through an effort combining proof-of-principle experiments with electromagnetic modeling. A small-scale folded CPFL was fabricated using surface-mount ceramic multilayer capacitors. The line consisted of 150 capacitors close-packed in parallel and delivered a 300 ns flat-top pulse. The concept was carried to a 10 kV class device using a polymer-ceramic nanocomposite dielectric with a permittivity of 37.6. The line was designed for a 161 ns FWHM length pulse into a matched load. The line delivered a 110 ns FWHM pulse, and the pulse peak amplitude exceeded the matched load ideal. Transient electromagnetic analysis using the particle-in-cell code ICEPIC was conducted to examine the nature of the unexpected pulse shortening and distortion. Two-dimensional analysis failed to capture the anomalous behavior. Three-dimensional analysis replicated the pulse shape and revealed that the bends were largely responsible for the pulse shortening. The bends not only create the expected reflection of the incident TEM wave but also produce a non-zero component of the Poynting vector perpendicular to the propagation direction of the dominant electromagnetic wave, resulting in power flow largely external to the PFL. This analysis explains both the pulse shortening and the amplitude of the pulse.

Analysis of folded pulse forming line operation

NASA Astrophysics Data System (ADS)

Domonkos, M. T.; Watrous, J.; Parker, J. V.; Cavazos, T.; Slenes, K.; Heidger, S.; Brown, D.; Wilson, D.

2014-09-01

A compact pulse forming line (CPFL) concept based on a folded transmission line and high-breakdown strength dielectric was explored through an effort combining proof-of-principle experiments with electromagnetic modeling. A small-scale folded CPFL was fabricated using surface-mount ceramic multilayer capacitors. The line consisted of 150 capacitors close-packed in parallel and delivered a 300 ns flat-top pulse. The concept was carried to a 10 kV class device using a polymer-ceramic nanocomposite dielectric with a permittivity of 37.6. The line was designed for a 161 ns FWHM length pulse into a matched load. The line delivered a 110 ns FWHM pulse, and the pulse peak amplitude exceeded the matched load ideal. Transient electromagnetic analysis using the particle-in-cell code ICEPIC was conducted to examine the nature of the unexpected pulse shortening and distortion. Two-dimensional analysis failed to capture the anomalous behavior. Three-dimensional analysis replicated the pulse shape and revealed that the bends were largely responsible for the pulse shortening. The bends not only create the expected reflection of the incident TEM wave but also produce a non-zero component of the Poynting vector perpendicular to the propagation direction of the dominant electromagnetic wave, resulting in power flow largely external to the PFL. This analysis explains both the pulse shortening and the amplitude of the pulse.

Biopsy using a Magnetic Capsule Endoscope Carrying, Releasing, and Retrieving Untethered Microgrippers

PubMed Central

Yim, Sehyuk; Gultepe, Evin; Gracias, David H.

2014-01-01

This paper proposes a new wireless biopsy method where a magnetically actuated untethered soft capsule endoscope carries and releases a large number of thermo-sensitive, untethered microgrippers (μ-grippers) at a desired location inside the stomach and retrieves them after they self-fold and grab tissue samples. We describe the working principles and analytical models for the μ-gripper release and retrieval mechanisms, and evaluate the proposed biopsy method in ex vivo experiments. This hierarchical approach combining the advanced navigation skills of centimeter-scaled untethered magnetic capsule endoscopes with highly parallel, autonomous, submillimeter scale tissue sampling μ-grippers offers a multifunctional strategy for gastrointestinal capsule biopsy. PMID:24108454

A Computationally Efficient Hypothesis Testing Method for Epistasis Analysis using Multifactor Dimensionality Reduction

PubMed Central

Pattin, Kristine A.; White, Bill C.; Barney, Nate; Gui, Jiang; Nelson, Heather H.; Kelsey, Karl R.; Andrew, Angeline S.; Karagas, Margaret R.; Moore, Jason H.

2008-01-01

Multifactor dimensionality reduction (MDR) was developed as a nonparametric and model-free data mining method for detecting, characterizing, and interpreting epistasis in the absence of significant main effects in genetic and epidemiologic studies of complex traits such as disease susceptibility. The goal of MDR is to change the representation of the data using a constructive induction algorithm to make nonadditive interactions easier to detect using any classification method such as naïve Bayes or logistic regression. Traditionally, MDR constructed variables have been evaluated with a naïve Bayes classifier that is combined with 10-fold cross validation to obtain an estimate of predictive accuracy or generalizability of epistasis models. Traditionally, we have used permutation testing to statistically evaluate the significance of models obtained through MDR. The advantage of permutation testing is that it controls for false-positives due to multiple testing. The disadvantage is that permutation testing is computationally expensive. This is in an important issue that arises in the context of detecting epistasis on a genome-wide scale. The goal of the present study was to develop and evaluate several alternatives to large-scale permutation testing for assessing the statistical significance of MDR models. Using data simulated from 70 different epistasis models, we compared the power and type I error rate of MDR using a 1000-fold permutation test with hypothesis testing using an extreme value distribution (EVD). We find that this new hypothesis testing method provides a reasonable alternative to the computationally expensive 1000-fold permutation test and is 50 times faster. We then demonstrate this new method by applying it to a genetic epidemiology study of bladder cancer susceptibility that was previously analyzed using MDR and assessed using a 1000-fold permutation test. PMID:18671250

A plea for geometrical order in tectonics

NASA Astrophysics Data System (ADS)

Schmid, Stefan

2017-04-01

Ever since publishing his landmark book "Folding and Fracturing of Rocks" 50 years ago John G. Ramsay (Ramsay 1967) has fascinated many of us with his stringent mathematical-geometrical approach towards analyzing finite strain in rocks, in particular what the geometry and kinematics of folding are concerned. The figures in this early book, as well as John's drawings and photographs published in later books and articles, undoubtedly also impressed many of us by their sheer aesthetic value. This book and his later work conveyed the message that rock deformation behaves in an "orderly" way, a message that is shared by many, but not all, of John's colleagues in structural geology and tectonics. This contribution is a plea for careful structural analysis and extensive fieldwork, providing the indispensable base in any attempt to go further and also understand the physics of rock deformation and geological processes at all scales. Two large-scale examples will be discussed in this respect: (1) The problem of mélanges in an ophiolite-bearing unit of the Swiss Alps (Arosa Zone) showing that careful structural analysis leads to the view that such chaotic mélanges were postulated by some authors in the absence of a carful structural analysis, and that the geometry in fact is a result of polyphase deformation, and (2) the problem of orogen scale transects of across the Alps that reflect an amazing degree of order in the stacking of diverse paleogeographical units enabling geometrical-kinematic attempts of retrodeformation and contrasting with alternative and rather "chaotic" views. Reference: Ramsay, J.G. 1967: Folding and Fracturing of Rocks. McGraw-Hill New York, 568pp.

Protein Folding Using a Vortex Fluidic Device.

PubMed

Britton, Joshua; Smith, Joshua N; Raston, Colin L; Weiss, Gregory A

2017-01-01

Essentially all biochemistry and most molecular biology experiments require recombinant proteins. However, large, hydrophobic proteins typically aggregate into insoluble and misfolded species, and are directed into inclusion bodies. Current techniques to fold proteins recovered from inclusion bodies rely on denaturation followed by dialysis or rapid dilution. Such approaches can be time consuming, wasteful, and inefficient. Here, we describe rapid protein folding using a vortex fluidic device (VFD). This process uses mechanical energy introduced into thin films to rapidly and efficiently fold proteins. With the VFD in continuous flow mode, large volumes of protein solution can be processed per day with 100-fold reductions in both folding times and buffer volumes.

Reproducibility of Fluorescent Expression from Engineered Biological Constructs in E. coli

PubMed Central

Beal, Jacob; Haddock-Angelli, Traci; Gershater, Markus; de Mora, Kim; Lizarazo, Meagan; Hollenhorst, Jim; Rettberg, Randy

2016-01-01

We present results of the first large-scale interlaboratory study carried out in synthetic biology, as part of the 2014 and 2015 International Genetically Engineered Machine (iGEM) competitions. Participants at 88 institutions around the world measured fluorescence from three engineered constitutive constructs in E. coli. Few participants were able to measure absolute fluorescence, so data was analyzed in terms of ratios. Precision was strongly related to fluorescent strength, ranging from 1.54-fold standard deviation for the ratio between strong promoters to 5.75-fold for the ratio between the strongest and weakest promoter, and while host strain did not affect expression ratios, choice of instrument did. This result shows that high quantitative precision and reproducibility of results is possible, while at the same time indicating areas needing improved laboratory practices. PMID:26937966

Library Resources for Bac End Sequencing. Final Technical Report

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

Pieter J. de Jong

2000-10-01

Studies directed towards the specific aims outlined for this research award are summarized. The RPCI II Human Bac Library has been expanded by the addition of 6.9-fold genomic coverage. This segment has been generated from a MBOI partial digest of the same anonymous donor DNA used for the rest of the library. A new cloning vector, pTARBAC1, has been constructed and used in the construction of RPCI-II segment 5. This new cloning vector provides a new strategy in identifying targeted genomic regions and will greatly facilitate a large-scale analysis for positional cloning. A new maleCS7BC/6J mouse BAC library has beenmore » constructed. RPCI-23 contain 576 plates (approx 210,000 clones) and represents approximately 11-fold coverage of the mouse genome.« less

The generation of magnetic fields and electric currents in cometary plasma tails

NASA Technical Reports Server (NTRS)

Ip, W.-H.; Mendis, D. A.

1976-01-01

Due to the folding of the interplanetary magnetic field into the tail as a comet sweeps through the interplanetary medium, the magnetic field in the tail can be built up to the order of 100 gammas at a heliocentric distance of about 1 AU. This folding of magnetic flux tubes also results in a cross-tail electric current passing through a neutral sheet. When streams of enhanced plasma density merge with the main tail, cross-tail currents as large as 1 billion A may result. A condition could arise which causes a significant fraction of this current to be discharged through the inner coma, resulting in rapid ionization. The typical time scale for such outbursts of ionization is estimated to be of the order of 10,000 sec, which is in reasonable agreement with observation.

Role of special cross-links in structure formation of bacterial DNA polymer

NASA Astrophysics Data System (ADS)

Agarwal, Tejal; Manjunath, G. P.; Habib, Farhat; Lakshmi Vaddavalli, Pavana; Chatterji, Apratim

2018-01-01

Using data from contact maps of the DNA-polymer of Escherichia coli (E. Coli) (at kilobase pair resolution) as an input to our model, we introduce cross-links between monomers in a bead-spring model of a ring polymer at very specific points along the chain. Via suitable Monte Carlo simulations, we show that the presence of these cross-links leads to a particular organization of the chain at large (micron) length scales of the DNA. We also investigate the structure of a ring polymer with an equal number of cross-links at random positions along the chain. We find that though the polymer does get organized at the large length scales, the nature of the organization is quite different from the organization observed with cross-links at specific biologically determined positions. We used the contact map of E. Coli bacteria which has around 4.6 million base pairs in a single circular chromosome. In our coarse-grained flexible ring polymer model, we used 4642 monomer beads and observed that around 80 cross-links are enough to induce the large-scale organization of the molecule accounting for statistical fluctuations caused by thermal energy. The length of a DNA chain even of a simple bacterial cell such as E. Coli is much longer than typical proteins, hence we avoided methods used to tackle protein folding problems. We define new suitable quantities to identify the large scale structure of a polymer chain with a few cross-links.

Standard Transistor Array (STAR). Volume 1: Placement technique

NASA Technical Reports Server (NTRS)

Cox, G. W.; Caroll, B. D.

1979-01-01

A large scale integration (LSI) technology, the standard transistor array uses a prefabricated understructure of transistors and a comprehensive library of digital logic cells to allow efficient fabrication of semicustom digital LSI circuits. The cell placement technique for this technology involves formation of a one dimensional cell layout and "folding" of the one dimensional placement onto the chip. It was found that, by use of various folding methods, high quality chip layouts can be achieved. Methods developed to measure of the "goodness" of the generated placements include efficient means for estimating channel usage requirements and for via counting. The placement and rating techniques were incorporated into a placement program (CAPSTAR). By means of repetitive use of the folding methods and simple placement improvement strategies, this program provides near optimum placements in a reasonable amount of time. The program was tested on several typical LSI circuits to provide performance comparisons both with respect to input parameters and with respect to the performance of other placement techniques. The results of this testing indicate that near optimum placements can be achieved by use of the procedures incurring severe time penalties.

Interference of lithospheric folding in western Central Asia by simultaneous Indian and Arabian plate indentation

NASA Astrophysics Data System (ADS)

Smit, J. H. W.; Cloetingh, S. A. P. L.; Burov, E.; Tesauro, M.; Sokoutis, D.; Kaban, M.

2013-08-01

Large-scale intraplate deformation of the crust and the lithosphere in Central Asia as a result of the indentation of India has been extensively documented. In contrast, the impact of continental collision between Arabia and Eurasia on lithosphere tectonics in front of the main suture zone, has received much less attention. The resulting Neogene shortening and uplift of the external Zagros, Alborz, Kopeh Dagh and Caucasus Mountain belts in Iran and surrounding areas is characterised by a simultaneous onset of major topography growth at ca. 5 Ma. At the same time, subsidence accelerated in the adjacent Caspian, Turan and Amu Darya basins. We present evidence for interference of lithospheric folding patterns induced by the Arabian and Indian collision with Eurasia. Wavelengths and spatial patterns are inferred from satellite-derived topography and gravity models. The observed interference of the patterns of folding appears to be primarily the result of spatial orientation of the two indenters, differences in their convergence velocities and the thermo-mechanical structure of the lithosphere west and east of the Kugitang-Tunka Line.

How the folding rates of two- and multistate proteins depend on the amino acid properties.

PubMed

Huang, Jitao T; Huang, Wei; Huang, Shanran R; Li, Xin

2014-10-01

Proteins fold by either two-state or multistate kinetic mechanism. We observe that amino acids play different roles in different mechanism. Many residues that are easy to form regular secondary structures (α helices, β sheets and turns) can promote the two-state folding reactions of small proteins. Most of hydrophilic residues can speed up the multistate folding reactions of large proteins. Folding rates of large proteins are equally responsive to the flexibility of partial amino acids. Other properties of amino acids (including volume, polarity, accessible surface, exposure degree, isoelectric point, and phase transfer energy) have contributed little to folding kinetics of the proteins. Cysteine is a special residue, it triggers two-state folding reaction and but inhibits multistate folding reaction. These findings not only provide a new insight into protein structure prediction, but also could be used to direct the point mutations that can change folding rate. © 2014 Wiley Periodicals, Inc.

Evolution of the Alpine Tethys (Sava) suture zone in Fruška Gora Mountains (N Serbia): from orogenic building to tectonic omissions

NASA Astrophysics Data System (ADS)

Toljić, Marinko; Matenco, Liviu; ĐErić, Nevenka; Milivojević, Jelena; Gerzina, Nataša.; Stojadinović, Uros

2010-05-01

The Fru\\vska Gora Mountains in northern Serbia offers an unique opportunity to study the Cretaceous-Eocene evolution of the NE part of the Dinarides, which is largely covered elsewhere beneath the thick Miocene sediments of the Pannonian basin, deposited during the back-arc collapse associated with the subduction and roll-back recorded in the external Carpathians. The structural grain of the Fru\\vska Gora Mountains is the one of a large scale antiform, exposing a complex puzzle of highly deformed metamorphic rocks in its centre and Triassic-Miocene sequence of non-metamorphosed sediments, ophiolites and volcanics along its flanks. The metamorphic rocks were the target of structural investigations coupled with paleontological dating (conodonts, palynomorphs and radiolarians) in an effort to unravel the geodynamic evolution of an area thought to be located near the suture zone between the Tisza upper plate and the Adriatic lower plate, i.e. the Sava subduction zone of the Dinarides (e.g., Pamic, 2002; Schmid et al., 2008). The existence of this subduction zone was previously inferred here by local observations, such as metamorphosed Mesozoic sediments containing Middle Triassic conodonts (Đurđanović, 1971) or Early Cretaceous blue schists metamorphism (123±5 Ma, Milovanović et al., 1995). The metamorphic sequence is characterized by a Paleozoic age meta-sedimentary basement which contains palynomorphs of Upper Paleozoic - Carboniferous age and a meta-sedimentary and meta-volcanic sequence which contain a succession of contrasting metamorphosed lithologies such sandstones, black limestones, shallow water white limestones, basic volcanic sequences, deep nodular limestiones, radiolarites, meta-ophiolites and turbiditic sequences. The lower part of the sequence is contrastingly similar with the Triassic cover of the Drina-Ivanijca thrust sheet and its metamorphosed equivalent observed in the Kopaonik and Studenica series (Schefer et al., in press). This observation is supported by the newly found micro-fauna of Upper Triassic in age in the meta-sandstones associated with meta-volcanics on the SW slopes of the mountain. The upper part of the sequence display metamorphosed "flysh"-type of sequences and meta-basalts. In these deposits, slightly metamorphosed siliciclastics (lithic sandstones with volcanic-derived clasts) previously interpreted as Upper Jurassic mélange have proved to contain Upper Cretaceous palynomorphs. Among the rocks exposed in the metamorphic core of the mountains, the SW slope of Fru\\vska Gora offers the optimal locality for the study of the kinematic evolution. Here, four phases of folding have been mapped, being associated mainly with large-scale regional contraction. The first phase is characterized by isoclinal folding, with reconstructed SW vergence. The second generation of E-W oriented and coaxial folds is asymmetric and is up to metres in size, displaying a south vergence and has largely refolded the previous generation. The third event was responsible for the formation of upright folds, yet again E-W oriented, re-folding earlier structures. The first two phases of folding are associated with metamorphic conditions, while the third was apparently near the transition with the brittle domain. The relationship with a fourth folding event observed also in the non-metamorphosed clastic-carbonate rocks is rather uncertain, but is apparently associated with the present day antiformal structure of the Fuska Gora Mountains. Interestingly, the metamorphosed Triassic and Upper Cretaceous carbonatic-clastic sequence in the core of the antiform is in structural contact along the antiformal flanks with Lower-Middle Triassic and Upper Cretaceous-Paleogene sediments which display the same facies, but these are not metamorphosed. This demonstrates a large scale tectonic omission along the flanks of the Fru\\vska Gora antiform, 9-10km of rocks being removed by what we speculatively define as an extensional detachment exhuming the metamorphic core. This detachment has been subsequently folded into the present-day antiformal geometry of the Fru\\vska Gora Mountains. These findings demonstrate that the metamorphic and non-metamorphic Upper Cretaceous - Paleogene clastic-carbonate sediments belongs to the main Alpine Tethys (Sava) subduction zone of the Dinarides. The Paleozoic-Triassic metamorphic and non-metamorphic rocks belong to the distal Adriatic lower plate, or more precisely to the Jadar-Kopaonik composite thrust sheet (Schmid et al., 2008), while the layer of serpentinized peridotite found at their contact most probably belongs to the Western Vardar ophiolites obducted over the Adriatic plate during Late Jurassic - Earliest Cretaceous. The distal Jadar-Kopaonik composite unit was partly affected by strong contractional deformation and a Late Eocene greenschist facies metamorphism during the main phase of subduction and collision, similarly to what has been observed elsewhere in the Dinarides (Pamić, 2002; Schefer et al., in press). A Miocene phase of core-complex formation was responsible for the large tectonic omission observed, being probably followed by the formation of a wide open antiformal structure during the Pliocene-Quaternary inversion of the Pannonian basin.

Proterozoic deformation of the East Saharan Craton in Southeast Libya, South Egypt and North Sudan

NASA Astrophysics Data System (ADS)

Schandelmeier, H.; Richter, A.; Harms, U.

1987-09-01

The basement areas in Southeast Libya, South Egypt and North Sudan, west of the Nile, between Gebel Uweinat and the Bayuda Desert, are part of an approximately 1000-km-wide, complexly folded, polymetamorphic zone with a regional N-NNE-NE-ENE trend of foliation and fold axis. Since this belt extends southwestward into the area of Zalingei in the southern Darfur block (West Sudan), it is named the Northern Zalingei fold zone. Sr and Nd isotopic studies suggest that this zone is older than Pan-African and further indicate that, apart from Archean rocks in the Gebel Uweinat area, this belt is of Early-Middle Proterozoic age. An Early-Middle Proterozoic three-stage deformational and anatectic event established the present-day fold and fault geometry in the western parts of this zone in the Gebel Uweinat—Gebel Kamil area. The Pan-African tectono-thermal episode was most effective in the eastern part of the belt, near the boundary with the Nubian Shield volcano-sedimentary-ophiolite-granitoid assemblages. It caused migmatization, granite emplacement, mylonitization and large-scale wrench faulting which was related to Late Proterozoic accretionary and collisional events of the Arabian-Nubian Shield with the margin of the East Saharan Craton.

Two-step crystal growth mechanism during crystallization of an undercooled Ni50Al50 alloy

NASA Astrophysics Data System (ADS)

An, Simin; Li, Jiahao; Li, Yang; Li, Shunning; Wang, Qi; Liu, Baixin

2016-08-01

Crystallization processes are always accompanied by the emergence of multiple intermediate states, of which the structures and transition dynamics are far from clarity, since it is difficult to experimentally observe the microscopic pathway. To insight the structural evolution and the crystallization dynamics, we perform large-scale molecular dynamics simulations to investigate the time-dependent crystallization behavior of the NiAl intermetallic upon rapid solidification. The simulation results reveal that the crystallization process occurs via a two-step growth mechanism, involving the formation of initial non-equilibrium long range order (NLRO) regions and of the subsequent equilibrium long range order (ELRO) regions. The formation of the NLRO regions makes the grains rather inhomogeneous, while the rearrangement of the NLRO regions into the ELRO regions makes the grains more ordered and compact. This two-step growth mechanism is actually controlled by the evolution of the coordination polyhedra, which are characterized predominantly by the transformation from five-fold symmetry to four-fold and six-fold symmetry. From liquids to NLRO and further to ELRO, the five-fold symmetry of these polyhedra gradually fades, and finally vanishes when B2 structure is distributed throughout the grain bulk. The energy decrease along the pathway further implies the reliability of the proposed crystallization processes.

Large-scale structure prediction by improved contact predictions and model quality assessment.

PubMed

Michel, Mirco; Menéndez Hurtado, David; Uziela, Karolis; Elofsson, Arne

2017-07-15

Accurate contact predictions can be used for predicting the structure of proteins. Until recently these methods were limited to very big protein families, decreasing their utility. However, recent progress by combining direct coupling analysis with machine learning methods has made it possible to predict accurate contact maps for smaller families. To what extent these predictions can be used to produce accurate models of the families is not known. We present the PconsFold2 pipeline that uses contact predictions from PconsC3, the CONFOLD folding algorithm and model quality estimations to predict the structure of a protein. We show that the model quality estimation significantly increases the number of models that reliably can be identified. Finally, we apply PconsFold2 to 6379 Pfam families of unknown structure and find that PconsFold2 can, with an estimated 90% specificity, predict the structure of up to 558 Pfam families of unknown structure. Out of these, 415 have not been reported before. Datasets as well as models of all the 558 Pfam families are available at http://c3.pcons.net/ . All programs used here are freely available. arne@bioinfo.se. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Evolutionary Strategies for Protein Folding

NASA Astrophysics Data System (ADS)

Murthy Gopal, Srinivasa; Wenzel, Wolfgang

2006-03-01

The free energy approach for predicting the protein tertiary structure describes the native state of a protein as the global minimum of an appropriate free-energy forcefield. The low-energy region of the free-energy landscape of a protein is extremely rugged. Efficient optimization methods must therefore speed up the search for the global optimum by avoiding high energy transition states, adapt large scale moves or accept unphysical intermediates. Here we investigate an evolutionary strategies(ES) for optimizing a protein conformation in our all-atom free-energy force field([1],[2]). A set of random conformations is evolved using an ES to get a diverse population containing low energy structure. The ES is shown to balance energy improvement and yet maintain diversity in structures. The ES is implemented as a master-client model for distributed computing. Starting from random structures and by using this optimization technique, we were able to fold a 20 amino-acid helical protein and 16 amino-acid beta hairpin[3]. We compare ES to basin hopping method. [1]T. Herges and W. Wenzel,Biophys.J. 87,3100(2004) [2] A. Verma and W. Wenzel Stabilization and folding of beta-sheet and alpha-helical proteins in an all-atom free energy model(submitted)(2005) [3] S. M. Gopal and W. Wenzel Evolutionary Strategies for Protein Folding (in preparation)

Biomolecular Dynamics: Order-Disorder Transitions and Energy Landscapes

PubMed Central

Whitford, Paul C.; Sanbonmatsu, Karissa Y.; Onuchic, José N.

2013-01-01

While the energy landscape theory of protein folding is now a widely accepted view for understanding how relatively-weak molecular interactions lead to rapid and cooperative protein folding, such a framework must be extended to describe the large-scale functional motions observed in molecular machines. In this review, we discuss 1) the development of the energy landscape theory of biomolecular folding, 2) recent advances towards establishing a consistent understanding of folding and function, and 3) emerging themes in the functional motions of enzymes, biomolecular motors, and other biomolecular machines. Recent theoretical, computational, and experimental lines of investigation are providing a very dynamic picture of biomolecular motion. In contrast to earlier ideas, where molecular machines were thought to function similarly to macroscopic machines, with rigid components that move along a few degrees of freedom in a deterministic fashion, biomolecular complexes are only marginally stable. Since the stabilizing contribution of each atomic interaction is on the order of the thermal fluctuations in solution, the rigid body description of molecular function must be revisited. An emerging theme is that functional motions encompass order-disorder transitions and structural flexibility provide significant contributions to the free-energy. In this review, we describe the biological importance of order-disorder transitions and discuss the statistical-mechanical foundation of theoretical approaches that can characterize such transitions. PMID:22790780

26. CURRENT METERS WITH FOLDING SCALE (MEASURED IN INCHES) IN ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

26. CURRENT METERS WITH FOLDING SCALE (MEASURED IN INCHES) IN FOREGROUND: GURLEY MODEL NO. 665 AT CENTER, GURLEY MODEL NO. 625 'PYGMY' CURRENT METER AT LEFT, AND WES MINIATURE PRICE-TYPE CURRENT METER AT RIGHT. - Waterways Experiment Station, Hydraulics Laboratory, Halls Ferry Road, 2 miles south of I-20, Vicksburg, Warren County, MS

Assessment of MRI-Based Automated Fetal Cerebral Cortical Folding Measures in Prediction of Gestational Age in the Third Trimester.

PubMed

Wu, J; Awate, S P; Licht, D J; Clouchoux, C; du Plessis, A J; Avants, B B; Vossough, A; Gee, J C; Limperopoulos, C

2015-07-01

Traditional methods of dating a pregnancy based on history or sonographic assessment have a large variation in the third trimester. We aimed to assess the ability of various quantitative measures of brain cortical folding on MR imaging in determining fetal gestational age in the third trimester. We evaluated 8 different quantitative cortical folding measures to predict gestational age in 33 healthy fetuses by using T2-weighted fetal MR imaging. We compared the accuracy of the prediction of gestational age by these cortical folding measures with the accuracy of prediction by brain volume measurement and by a previously reported semiquantitative visual scale of brain maturity. Regression models were constructed, and measurement biases and variances were determined via a cross-validation procedure. The cortical folding measures are accurate in the estimation and prediction of gestational age (mean of the absolute error, 0.43 ± 0.45 weeks) and perform better than (P = .024) brain volume (mean of the absolute error, 0.72 ± 0.61 weeks) or sonography measures (SDs approximately 1.5 weeks, as reported in literature). Prediction accuracy is comparable with that of the semiquantitative visual assessment score (mean, 0.57 ± 0.41 weeks). Quantitative cortical folding measures such as global average curvedness can be an accurate and reliable estimator of gestational age and brain maturity for healthy fetuses in the third trimester and have the potential to be an indicator of brain-growth delays for at-risk fetuses and preterm neonates. © 2015 by American Journal of Neuroradiology.

Width of surface rupture zone for thrust earthquakes: implications for earthquake fault zoning

NASA Astrophysics Data System (ADS)

Boncio, Paolo; Liberi, Francesca; Caldarella, Martina; Nurminen, Fiia-Charlotta

2018-01-01

The criteria for zoning the surface fault rupture hazard (SFRH) along thrust faults are defined by analysing the characteristics of the areas of coseismic surface faulting in thrust earthquakes. Normal and strike-slip faults have been deeply studied by other authors concerning the SFRH, while thrust faults have not been studied with comparable attention. Surface faulting data were compiled for 11 well-studied historic thrust earthquakes occurred globally (5.4 ≤ M ≤ 7.9). Several different types of coseismic fault scarps characterize the analysed earthquakes, depending on the topography, fault geometry and near-surface materials (simple and hanging wall collapse scarps, pressure ridges, fold scarps and thrust or pressure ridges with bending-moment or flexural-slip fault ruptures due to large-scale folding). For all the earthquakes, the distance of distributed ruptures from the principal fault rupture (r) and the width of the rupture zone (WRZ) were compiled directly from the literature or measured systematically in GIS-georeferenced published maps. Overall, surface ruptures can occur up to large distances from the main fault ( ˜ 2150 m on the footwall and ˜ 3100 m on the hanging wall). Most of the ruptures occur on the hanging wall, preferentially in the vicinity of the principal fault trace ( > ˜ 50 % at distances < ˜ 250 m). The widest WRZ are recorded where sympathetic slip (Sy) on distant faults occurs, and/or where bending-moment (B-M) or flexural-slip (F-S) fault ruptures, associated with large-scale folds (hundreds of metres to kilometres in wavelength), are present. A positive relation between the earthquake magnitude and the total WRZ is evident, while a clear correlation between the vertical displacement on the principal fault and the total WRZ is not found. The distribution of surface ruptures is fitted with probability density functions, in order to define a criterion to remove outliers (e.g. 90 % probability of the cumulative distribution function) and define the zone where the likelihood of having surface ruptures is the highest. This might help in sizing the zones of SFRH during seismic microzonation (SM) mapping. In order to shape zones of SFRH, a very detailed earthquake geologic study of the fault is necessary (the highest level of SM, i.e. Level 3 SM according to Italian guidelines). In the absence of such a very detailed study (basic SM, i.e. Level 1 SM of Italian guidelines) a width of ˜ 840 m (90 % probability from "simple thrust" database of distributed ruptures, excluding B-M, F-S and Sy fault ruptures) is suggested to be sufficiently precautionary. For more detailed SM, where the fault is carefully mapped, one must consider that the highest SFRH is concentrated in a narrow zone, ˜ 60 m in width, that should be considered as a fault avoidance zone (more than one-third of the distributed ruptures are expected to occur within this zone). The fault rupture hazard zones should be asymmetric compared to the trace of the principal fault. The average footwall to hanging wall ratio (FW : HW) is close to 1 : 2 in all analysed cases. These criteria are applicable to "simple thrust" faults, without considering possible B-M or F-S fault ruptures due to large-scale folding, and without considering sympathetic slip on distant faults. Areas potentially susceptible to B-M or F-S fault ruptures should have their own zones of fault rupture hazard that can be defined by detailed knowledge of the structural setting of the area (shape, wavelength, tightness and lithology of the thrust-related large-scale folds) and by geomorphic evidence of past secondary faulting. Distant active faults, potentially susceptible to sympathetic triggering, should be zoned as separate principal faults. The entire database of distributed ruptures (including B-M, F-S and Sy fault ruptures) can be useful in poorly known areas, in order to assess the extent of the area within which potential sources of fault displacement hazard can be present. The results from this study and the database made available in the Supplement can be used for improving the attenuation relationships for distributed faulting, with possible applications in probabilistic studies of fault displacement hazard.

Path Searching Based Crease Detection for Large Scale Scanned Document Images

NASA Astrophysics Data System (ADS)

Zhang, Jifu; Li, Yi; Li, Shutao; Sun, Bin; Sun, Jun

2017-12-01

Since the large size documents are usually folded for preservation, creases will occur in the scanned images. In this paper, a crease detection method is proposed to locate the crease pixels for further processing. According to the imaging process of contactless scanners, the shading on both sides of the crease usually varies a lot. Based on this observation, a convex hull based algorithm is adopted to extract the shading information of the scanned image. Then, the possible crease path can be achieved by applying the vertical filter and morphological operations on the shading image. Finally, the accurate crease is detected via Dijkstra path searching. Experimental results on the dataset of real scanned newspapers demonstrate that the proposed method can obtain accurate locations of the creases in the large size document images.

Good manufacturing practice-compliant cell sorting and large-scale expansion of single KIR-positive alloreactive human natural killer cells for multiple infusions to leukemia patients.

PubMed

Siegler, Uwe; Meyer-Monard, Sandrine; Jörger, Simon; Stern, Martin; Tichelli, André; Gratwohl, Alois; Wodnar-Filipowicz, Aleksandra; Kalberer, Christian P

2010-10-01

Alloreactive natural killer (NK) cells are potent effectors of innate anti-tumor defense. The introduction of NK cell-based immunotherapy to current treatment options in acute myeloid leukemia (AML) requires NK cell products with high anti-leukemic efficacy optimized for clinical use. We describe a good manufacturing practice (GMP)-compliant protocol of large-scale ex vivo expansion of alloreactive NK cells suitable for multiple donor lymphocyte infusions (NK-DLI) in AML. CliniMACS-purified NK cells were cultured in closed air-permeable culture bags with certified culture medium and components approved for human use [human serum, interleukin (IL)-2, IL-15 and anti-CD3 antibody] and with autologous irradiated feeder cells. NK cells (6.0 ± 1.2 x 10(8)) were purified from leukaphereses (8.1 ± 0.8 L) of six healthy donors and cultured under GMP conditions. NK cell numbers increased 117.0 ± 20.0-fold in 19 days. To reduce the culture volume associated with expansion of bulk NK cells and to expand selectively the alloreactive NK cell subsets, GMP-certified cell sorting was introduced to obtain cells with single killer immunoglobulin-like receptor (KIR) specificities. The subsequent GMP-compliant expansion of single KIR+ cells was 268.3 ± 66.8-fold, with a contaminating T-cell content of only 0.006 ± 0.002%. The single KIR-expressing NK cells were cytotoxic against HLA-mismatched primary AML blasts in vitro and effectively reduced tumor cell load in vivo in NOD/SCID mice transplanted with human AML. The approach to generating large numbers of GMP-grade alloreactive NK cells described here provides the basis for clinical efficacy trials of NK-DLI to complement and advance therapeutic strategies against human AML.

Large-scale Clinical-grade Retroviral Vector Production in a Fixed-Bed Bioreactor

PubMed Central

Wang, Xiuyan; Olszewska, Malgorzata; Qu, Jinrong; Wasielewska, Teresa; Bartido, Shirley; Hermetet, Gregory; Sadelain, Michel

2015-01-01

The successful genetic engineering of patient T cells with γ-retroviral vectors expressing chimeric antigen receptors or T-cell receptors for phase II clinical trials and beyond requires the large-scale manufacture of high-titer vector stocks. The production of retroviral vectors from stable packaging cell lines using roller bottles or 10- to 40-layer cell factories is limited by a narrow harvest window, labor intensity, open-system operations, and the requirement for significant incubator space. To circumvent these shortcomings, we optimized the production of vector stocks in a disposable fixed-bed bioreactor using good manufacturing practice–grade packaging cell lines. High-titer vector stocks were harvested over 10 days, representing a much broader harvest window than the 3-day harvest afforded by cell factories. For PG13 and 293Vec packaging cells, the average vector titer and the vector stocks’ yield in the bioreactor were higher by 3.2- to 7.3-fold, and 5.6- to 13.1-fold, respectively, than those obtained in cell factories. The vector production was 10.4 and 18.6 times more efficient than in cell factories for PG13 and 293Vec cells, respectively. Furthermore, the vectors produced from the fixed-bed bioreactors passed the release test assays for clinical applications. Therefore, a single vector lot derived from 293Vec is suitable to transduce up to 500 patients cell doses in the context of large clinical trials using chimeric antigen receptors or T-cell receptors. These findings demonstrate for the first time that a robust fixed-bed bioreactor process can be used to produce γ-retroviral vector stocks scalable up to the commercialization phase. PMID:25751502

Antigen presenting cell-mediated expansion of human umbilical cord blood yields log-scale expansion of natural killer cells with anti-myeloma activity.

PubMed

Shah, Nina; Martin-Antonio, Beatriz; Yang, Hong; Ku, Stephanie; Lee, Dean A; Cooper, Laurence J N; Decker, William K; Li, Sufang; Robinson, Simon N; Sekine, Takuya; Parmar, Simrit; Gribben, John; Wang, Michael; Rezvani, Katy; Yvon, Eric; Najjar, Amer; Burks, Jared; Kaur, Indreshpal; Champlin, Richard E; Bollard, Catherine M; Shpall, Elizabeth J

2013-01-01

Natural killer (NK) cells are important mediators of anti-tumor immunity and are active against several hematologic malignancies, including multiple myeloma (MM). Umbilical cord blood (CB) is a promising source of allogeneic NK cells but large scale ex vivo expansion is required for generation of clinically relevant CB-derived NK (CB-NK) cell doses. Here we describe a novel strategy for expanding NK cells from cryopreserved CB units using artificial antigen presenting feeder cells (aAPC) in a gas permeable culture system. After 14 days, mean fold expansion of CB-NK cells was 1848-fold from fresh and 2389-fold from cryopreserved CB with >95% purity for NK cells (CD56(+)/CD3(-)) and less than 1% CD3(+) cells. Though surface expression of some cytotoxicity receptors was decreased, aAPC-expanded CB-NK cells exhibited a phenotype similar to CB-NK cells expanded with IL-2 alone with respect to various inhibitory receptors, NKG2C and CD94 and maintained strong expression of transcription factors Eomesodermin and T-bet. Furthermore, CB-NK cells formed functional immune synapses with and demonstrated cytotoxicity against various MM targets. Finally, aAPC-expanded CB-NK cells showed significant in vivo activity against MM in a xenogenic mouse model. Our findings introduce a clinically applicable strategy for the generation of highly functional CB-NK cells which can be used to eradicate MM.

In-Situ Roughening of Polymeric Microstructures

PubMed Central

Shadpour, Hamed; Allbritton, Nancy L.

2010-01-01

A method to perform in-situ roughening of arrays of microstructures weakly adherent to an underlying substrate was presented. SU8, 1002F, and polydimethylsiloxane (PDMS) microstructures were roughened by polishing with a particle slurry. The roughness and the percentage of dislodged or damaged microstructures was evaluated as a function of the roughening time for both SU8 and 1002F structures. A maximal RMS roughness of 7-18 nm for the surfaces was obtained within 15 to 30 s of polishing with the slurry. This represented a 4-9 fold increase in surface roughness relative to that of the native surface. Less than 0.8% of the microstructures on the array were removed or damage after 5 min of polishing. Native and roughened arrays were assessed for their ability to support fibronectin adhesion and cell attachment and growth. The quantity of adherent fibronectin was increased on roughened arrays by two-fold over that on native arrays. Cell adhesion to the roughened surfaces was also increased compared to native surfaces. Surface roughening with the particle slurry also improved the ability to stamp molecules onto the substrate during microcontact printing. Roughening both the PDMS stamp and substrate resulted in up to a 20-fold improvement in the transfer of BSA-Alexa Fluor 647 from the stamp to the substrate. Thus roughening of micron-scale surfaces with a particle slurry increased the adhesion of biomolecules as well as cells to microstructures with little to no damage to large scale arrays of the structures. PMID:20423129

The frequency of perceived stress, anxiety, and depression in patients with common pathologies affecting voice.

PubMed

Dietrich, Maria; Verdolini Abbott, Katherine; Gartner-Schmidt, Jackie; Rosen, Clark A

2008-07-01

The study's objectives were to investigate (1) the frequency of perceived stress, anxiety, and depression for patients with common voice disorders, (2) the distribution of these variables by diagnosis, and (3) the distribution of the variables by gender. Retrospective data were derived from self-report questionnaires assessing recent stress (Perceived Stress Scale-10), anxiety, and depression (Hospital Anxiety and Depression Scale) in a cohort of new patients presenting to a voice clinic. Data are presented on 160 patients with muscle tension dysphonia (MTD), benign vocal fold lesions, paradoxical vocal fold movement disorder (PVFMD), or glottal insufficiency. Pooled data indicated that average stress, anxiety, and depression scores were similar to those found for the healthy population. However, 25.0%, 36.9%, and 31.2% of patients showed elevated stress, anxiety, and depression scores, respectively, compared to norms. Patients with PVFMD had the most frequent occurrence-and patients with glottal insufficiency had the least frequent occurrence of elevated stress, anxiety, and depression. Stress and depression were more common with MTD than with lesions, whereas reverse results were obtained for anxiety. More females than males had elevated stress, anxiety, and depression scores. The data are consistent with suggestions that stress, anxiety, and depression may be common among some patients with PVFMD, MTD, and vocal fold lesions and more common for women than men. However, individual variability in the data set was large. Further studies should evaluate the specific role of these conditions for selected categories of voice disorders in susceptible individuals.

Geologic map of Lake Mead and surrounding regions, southern Nevada, southwestern Utah, and northwestern Arizona

USGS Publications Warehouse

Felger, Tracey J.; Beard, Sue

2010-01-01

Regional stratigraphic units and structural features of the Lake Mead region are presented as a 1:250,000 scale map, and as a Geographic Information System database. The map, which was compiled from existing geologic maps of various scales, depicts geologic units, bedding and foliation attitudes, faults and folds. Units and structural features were generalized to highlight the regional stratigraphic and tectonic aspects of the geology of the Lake Mead region. This map was prepared in support of the papers presented in this volume, Special Paper 463, as well as to facilitate future investigations in the region. Stratigraphic units exposed within the area record 1800 million years of geologic history and include Proterozoic crystalline rocks, Paleozoic and Mesozoic sedimentary rocks, Mesozoic plutonic rocks, Cenozoic volcanic and intrusive rocks, sedimentary rocks and surfi cial deposits. Following passive margin sedimentation in the Paleozoic and Mesozoic, late Mesozoic (Sevier) thrusting and Late Cretaceous and early Tertiary compression produced major folding, reverse faulting, and thrust faulting in the Basin and Range, and resulted in regional uplift and monoclinal folding in the Colorado Plateau. Cenozoic extensional deformation, accompanied by sedimentation and volcanism, resulted in large-magnitude high- and low-angle normal faulting and strike-slip faulting in the Basin and Range; on the Colorado Plateau, extension produced north-trending high-angle normal faults. The latest history includes integration of the Colorado River system, dissection, development of alluvial fans, extensive pediment surfaces, and young faulting.

Improved purification of brine-shrimp (Artemia saline) (Na+ + K+)-activated adenosine triphosphatase and amino-acid and carbohydrate analyses of the isolated subunits.

PubMed Central

Peterson, G L; Hokin, L E

1980-01-01

Purification of the (Na+ + K+)-activated ATPase has been improved 2-fold the respect to both purity and yield over the previous method [Peterson, Ewing, Hootman & Conte (1978) J. Biol. Chem. 253, 4762-4770] by using Lubrol WX and non-denaturing concentrations of sodium dodecyl sulphate (SDS). The enzyme was purified 200-fold over the homogenate. The preparation had a specific activity of about 600 mumol of Pi/h per mg of protein, and was about 60% pure according to quantification of Coomassie Blue-stained SDS/polyacrylamide gels. The yield of purified enzyme was about 10 mg of protein per 100g of dry brine-shrimp (Artemia salina) cysts. The method is highly suitable for purification either on a small scale (10-25g of dry cysts) or on a large scale (900g of dry cysts) and methods are described for both. The large (Na+ + K+)-activated ATPase subunit (alpha-subunit) was isolated in pure form by SDS-gel filtration on Bio-Gel A 1.5m. The small subunit (beta-subunit) was eluted with other contaminating proteins on the Bio-Gel column, but was isolated in pure form by extraction from SDS/polyacrylamide gels. The amino acid and carbohydrate compositions of both subunits are reported. The alpha-subunit contained 5.2% carbohydrate by weight, and the beta-subunit 9.2%. Sialic acid was absent from both subunits. Images Fig. 3. Fig. 4. PMID:6272692

Clues to the formation of Enceladus' south-polar terrain from simulations of funiscular plains formation

NASA Astrophysics Data System (ADS)

Bland, M. T.; McKinnon, W. B.

2013-12-01

Cassini imaging and thermal data have demonstrated that Enceladus' four south-polar linear-fractures are the source of both Enceladus' cryovolcanic plume and its extreme thermal emission. These long (130 km), parallel 'tiger stripes' are located within a young, quasi-circular, south-polar depression characterized by extensive tectonic deformation that includes sets of both small-scale fractures (possibly relic tiger stripes) [Patthoff and Kattenhorn 2011], and large-amplitude circumferential ridges. Between the tiger stripes themselves are broad regions of periodic, low amplitude (50-100 m), short-wavelength (1 km) ridges (dubbed 'funiscular' terrain) that generally run parallel to the larger tiger stripe fractures but occasionally intersect them at small angles [Spencer et al. 2009]. The formation of the south polar terrain (SPT) may be related to localized melting of Enceladus' ice layer [e.g., Collins and Goodman, 2007] but the detailed formation kinematics of the SPT and its specific tectonic structures is far from certain. Here we constrain the formation of the SPT by simulating the development of funiscular terrain specifically. This terrain dominates the central portion of the SPT, including regions immediately adjacent to the tiger stripes. The stripes are, in effect, large-scale fractures imbedded within the funiscular terrain; thus, any kinematic or dynamic prescription for SPT formation must account for funiscular morphology. The simplest formation mechanism consistent with the funiscular ridges is that of low-amplitude, short-wavelength folding of a thin surface layer. Barr and Pruess [2010] demonstrated the plausibility of this mechanism using an analytical model developed for folds forming on lava flow tops. We extend their analysis using finite element modeling of the contraction of a thin, brittle lithosphere overlying ductile ice. We find fold morphologies consistent with the funiscular terrain (50-100 m amplitude, 1.5 km wavelengths) for lithospheric thicknesses of 250-500 m assuming weak (~100 kPa) near surface ice and 10% shortening. Creation of short wavelengths and tight fold hinges requires kinematic fold growth that shortens the fold wavelength subsequent to establishment of a longer, initial dominant wavelength. Thicker lithospheres (1 km) also reproduce the deformation if strains exceed 10%, though fold amplitudes are lower and wavelengths longer in this case. The thin lithosphere required to produce funiscular morphologies require exceedingly high heat flow if intact (low porosity) ice is assumed (≥1 W m-2). Significant lithospheric porosity that depresses the ice thermal conductivity (e.g., by a factor of ~3 for 30% porosity [Shoshany et al. 2002]) is likely required, and could decrease the necessary heat flux to ~300 mW m-2. The thin lithosphere necessary for its formation might account for the funiscular terrain's limited spatial extent adjacent to the tiger stripes, the locus of SPT thermal activity. A compressive stress regime between the tensile tiger stripes suggests local accommodation of strain in a dominantly extensional setting that is likely modulated by tidally-induced shear.

Simultaneous temporally resolved DPIV and pressure measurements of symmetric oscillations in a scaled-up vocal fold model

NASA Astrophysics Data System (ADS)

Ringenberg, Hunter; Rogers, Dylan; Wei, Nathaniel; Krane, Michael; Wei, Timothy

2017-11-01

The objective of this study is to apply experimental data to theoretical framework of Krane (2013) in which the principal aeroacoustic source is expressed in terms of vocal fold drag, glottal jet dynamic head, and glottal exit volume flow, reconciling formal theoretical aeroacoustic descriptions of phonation with more traditional lumped-element descriptions. These quantities appear in the integral equations of motion for phonatory flow. In this way time resolved velocity field measurements can be used to compute time-resolved estimates of the relevant terms in the integral equations of motion, including phonation aeroacoustic source strength. A simplified 10x scale vocal fold model from Krane, et al. (2007) was used to examine symmetric, i.e. `healthy', oscillatory motion of the vocal folds. By using water as the working fluid, very high spatial and temporal resolution was achieved. Temporal variation of transglottal pressure was simultaneously measured with flow on the vocal fold model mid-height. Experiments were dynamically scaled to examine a range of frequencies corresponding to male and female voice. The simultaneity of the pressure and flow provides new insights into the aeroacoustics associated with vocal fold oscillations. Supported by NIH Grant No. 2R01 DC005642-11.

LiveBench-1: continuous benchmarking of protein structure prediction servers.

PubMed

Bujnicki, J M; Elofsson, A; Fischer, D; Rychlewski, L

2001-02-01

We present a novel, continuous approach aimed at the large-scale assessment of the performance of available fold-recognition servers. Six popular servers were investigated: PDB-Blast, FFAS, T98-lib, GenTHREADER, 3D-PSSM, and INBGU. The assessment was conducted using as prediction targets a large number of selected protein structures released from October 1999 to April 2000. A target was selected if its sequence showed no significant similarity to any of the proteins previously available in the structural database. Overall, the servers were able to produce structurally similar models for one-half of the targets, but significantly accurate sequence-structure alignments were produced for only one-third of the targets. We further classified the targets into two sets: easy and hard. We found that all servers were able to find the correct answer for the vast majority of the easy targets if a structurally similar fold was present in the server's fold libraries. However, among the hard targets--where standard methods such as PSI-BLAST fail--the most sensitive fold-recognition servers were able to produce similar models for only 40% of the cases, half of which had a significantly accurate sequence-structure alignment. Among the hard targets, the presence of updated libraries appeared to be less critical for the ranking. An "ideally combined consensus" prediction, where the results of all servers are considered, would increase the percentage of correct assignments by 50%. Each server had a number of cases with a correct assignment, where the assignments of all the other servers were wrong. This emphasizes the benefits of considering more than one server in difficult prediction tasks. The LiveBench program (http://BioInfo.PL/LiveBench) is being continued, and all interested developers are cordially invited to join.

How rheological heterogeneities control the internal deformation of salt giants.

NASA Astrophysics Data System (ADS)

Raith, Alexander; Urai, Janos L.

2017-04-01

Salt giants, like the North European Zechstein, consist of several evaporation cycles of different evaporites with highly diverse rheologies. Common Potassium and Magnesium (K-Mg) salt are typically 10 to 100 times less viscous as halite while stringers consisting of anhydrite and carbonates are about 100 times more viscous. In most parts, these mechanically layered bodies experienced complex deformation, resulting in large scale internal folding with ruptured stringers and shear zones, as observed in seismic images. Furthermore, locally varying evaporation history produced different mechanical stratigraphies across the salt basin. Although most of these extraordinary soft or strong layers are rather thin (<100 m) compared to the dominating halite, we propose they have first order control on the deformation and the resulting structures inside salt bodies. Numerical models representing different mechanical stratigraphies of hard and soft layers inside a salt body were performed to analyze their influence on the internal deformation during lateral salt flow. The results show that a continuous or fractured stringer is folded and thrusted during salt contraction while soft K-Mg salt layers act as internal décollement. Depending on the viscosity of the fractured stringers, the shortening is mostly compensated by either folding or thrusting. This folding has large control over the internal structure of the salt body imposing a dominating wavelength to the whole structure during early deformation. Beside strong stringers, K-Mg salt layers also influence the deformation and salt flow inside the salt pillow. Strain is accumulated in the soft layers leading to stronger salt flow near these layers and extensive deformation inside of them. Thus, if a soft layer is present near a stringer, it will experience more deformation. Additionally, the strong strain concentration in the soft layers could decouple parts of the salt body from the main deformation.

Salt structures and vertical axis rotations; a case study in the Barbastro-Balaguer anticline, Southern Pyrenees.

NASA Astrophysics Data System (ADS)

Pueyo, Emilio L.; Oliván, Carlota; Soto, Ruth; Rodríguez-Pintó, Adriana; Santolaria, Pablo; Luzón, Aránzazu; Casas, Antonio M.; Ayala, Conxi

2017-04-01

Vertical axis rotations are common in all deformation settings. At larger scales, for example in fold and thrust belts, they are usually related to differential shortening along strike and this may be caused by a number of reasons (interplay of plate boundaries, sedimentary wedges, detachment level distribution, etc.). At smaller scales, local stress fields, interference of non-coaxial deformation phases, development of non-cylindrical structures, etc. may play an important role to accommodate significant magnitudes of rotation. Apart from their implication in the truly 4D understanding of geological structures, the occurrence of vertical axis rotation usually precludes the application of most 3D restoration techniques and thus, increases the uncertainty in any 3D reconstruction. Salt structures may form in different geological settings, but focusing on compressive regimes, very little is known about the relation between their geometry and kinematics and their ability to accommodate vertical axis rotations (i.e. local or regional lateral gradients of shortening). The Barbastro-Balaguer anticline (BBA) is the southernmost structure of the Central Pyrenees. It is a large detachment fold spreading more than 150 km along the front. In contrast to most frontal Pyrenean structures, the BBA is detached in Priabonian evaporites and was folded during Oligocene times as witnessed by well exposed growth strata. Along strike changes in the fold axis trend may reach 50°, an overall the anticline displays a convex shape towards the foreland (south). A residual Bouguer anomaly map based on a densely sampled gravimetric surveying (10.000 stations) has helped delineating a heterogeneous distribution of the Eocene detachment level in the subsurface. In this contribution we explore the interplay between vertical axis rotations, detachment level distribution and the fold geometry (structural trend and style based on hundreds of data). Seventy paleomagnetic sites evenly and densely distributed along the structure have been analyzed for this purpose. About 600 standard specimens have been thermally demagnetized in the Paleomagnetic Laboratory of the Burgos University (ASC TD48DC thermal demagnetizer and 2G superconducting magnetometer). Data processing has been carried out with the VPD program, applying standard PCA and virtual direction analyses. The ChRM directions passes the fold test and display two polarities, pointing to the primary character of the magnetization (key factor for the 3D restoration). This large dataset allows us to draw a robust network of rotation magnitudes along strike the western sector of the BBA that are key to understand its kinematics together to the aforementioned factors. We also pretend to use this network of vertical axis rotations to restore in 3D this salt structure.

Progress towards mapping the universe of protein folds

PubMed Central

Grant, Alastair; Lee, David; Orengo, Christine

2004-01-01

Although the precise aims differ between the various international structural genomics initiatives currently aiming to illuminate the universe of protein folds, many selectively target protein families for which the fold is unknown. How well can the current set of known protein families and folds be used to estimate the total number of folds in nature, and will structural genomics initiatives yield representatives for all the major protein families within a reasonable time scale? PMID:15128436

Folding of non-Euclidean curved shells

NASA Astrophysics Data System (ADS)

Bende, Nakul; Evans, Arthur; Innes-Gold, Sarah; Marin, Luis; Cohen, Itai; Santangelo, Christian; Hayward, Ryan

2015-03-01

Origami-based folding of 2D sheets has been of recent interest for a variety of applications ranging from deployable structures to self-folding robots. Though folding of planar sheets follows well-established principles, folding of curved shells involves an added level of complexity due to the inherent influence of curvature on mechanics. In this study, we use principles from differential geometry and thin shell mechanics to establish fundamental rules that govern folding of prototypical creased shells. In particular, we show how the normal curvature of a crease line controls whether the deformation is smooth or discontinuous, and investigate the influence of shell thickness and boundary conditions. We show that snap-folding of shells provides a route to rapid actuation on time-scales dictated by the speed of sound. The simple geometric design principles developed can be applied at any length-scale, offering potential for bio-inspired soft actuators for tunable optics, microfluidics, and robotics. This work was funded by the National Science Foundation through EFRI ODISSEI-1240441 with additional support to S.I.-G. through the UMass MRSEC DMR-0820506 REU program.

The Costs of Carnivory

PubMed Central

Carbone, Chris; Teacher, Amber; Rowcliffe, J. Marcus

2007-01-01

Mammalian carnivores fall into two broad dietary groups: smaller carnivores (<20 kg) that feed on very small prey (invertebrates and small vertebrates) and larger carnivores (>20 kg) that specialize in feeding on large vertebrates. We develop a model that predicts the mass-related energy budgets and limits of carnivore size within these groups. We show that the transition from small to large prey can be predicted by the maximization of net energy gain; larger carnivores achieve a higher net gain rate by concentrating on large prey. However, because it requires more energy to pursue and subdue large prey, this leads to a 2-fold step increase in energy expenditure, as well as increased intake. Across all species, energy expenditure and intake both follow a three-fourths scaling with body mass. However, when each dietary group is considered individually they both display a shallower scaling. This suggests that carnivores at the upper limits of each group are constrained by intake and adopt energy conserving strategies to counter this. Given predictions of expenditure and estimates of intake, we predict a maximum carnivore mass of approximately a ton, consistent with the largest extinct species. Our approach provides a framework for understanding carnivore energetics, size, and extinction dynamics. PMID:17227145

Borehole and High-Resolution Seismic Reflection Evidence for Holocene Activity on the Compton Blind-Thrust Fault, Los Angeles Basin, California

NASA Astrophysics Data System (ADS)

Leon, L. A.; Dolan, J. F.; Shaw, J. H.; Pratt, T. L.

2006-12-01

Newly collected borehole and high-resolution seismic reflection data from a site ~6 km south of downtown Los Angeles demonstrate that the Compton blind-thrust fault has generated multiple large-magnitude earthquakes during the Holocene. This large blind thrust fault, which was originally identified by Shaw and Suppe (1996) using industry seismic reflection profiles and well data, extends northwest-southeast for 40 km beneath the western edge of the Los Angeles basin. The industry seismic reflection data define a growth fault-bend fold associated with the thrust ramp, which, combined with well data, reveal compelling evidence for Pliocene and Pleistocene activity. The industry data, however, do not image deformation in the uppermost few hundred meters. In order to bridge this gap, we acquired high-resolution seismic reflection profiles at two scales across the back limb active axial surface of the fault-bend fold above the Compton thrust ramp, using a truck-mounted weight drop and sledgehammer sources. These profiles delineate the axial surfaces of the fold from <20 m depth downward to overlap with the upper part of the industry reflection data within the upper 500 m. The seismic reflection data reveal an upward-narrowing zone of folding that extends to <100 m of the surface. These data, in turn, allowed us to accurately and efficiently site a fault-perpendicular transect of eight continuously cored boreholes across the axial surface of the fold observed in both industry and high-resolution seismic reflection data. The borehole data reveal folding within a discrete kink band that is <~150 m wide in the shallow subsurface. Preliminary analysis of the deformed, shallow growth strata reveals evidence for a number of discrete uplift events, which we interpret as having occurred during several large-magnitude (M >7) earthquakes on the Compton fault. Although we do not as yet have age control for this transect, numerous organic-rich clay and silt layers, as well as abundant detrital charcoal, should yield 14C dates that will allow us to accurately date these uplift events. A stratigraphically abrupt downward transition from an upper section dominated by clays, silts, and sands into a gravel-dominated lower section occurs at ~25 m depth. If this transition is similar in age to well-dated sections elsewhere in the Los Angeles region (e.g. our Carfax site along the Puente Hills Thrust fault), then it marks the Pleistocene-Holocene change in climate and stream power at ~9.5 ¨C 10 ka. The total uplift across the Holocene/Pleistocene boundary is ~8 m, yielding a minimum uplift rate of ~0.8 mm/yr, which in turn suggests a slip rate on the blind thrust of 1.5 to 2 mm/yr. The depth of the shallowest buried fold scarp (1 m) attests to the recency of the youngest large-magnitude earthquake on the Compton blind-thrust fault. These observations clearly indicate that the Compton fault is active and capable of producing damaging, large-magnitude earthquakes directly beneath metropolitan Los Angeles.

Amyloid Polymorphism in the Protein Folding and Aggregation Energy Landscape.

PubMed

Adamcik, Jozef; Mezzenga, Raffaele

2018-02-15

Protein folding involves a large number of steps and conformations in which the folding protein samples different thermodynamic states characterized by local minima. Kinetically trapped on- or off-pathway intermediates are metastable folding intermediates towards the lowest absolute energy minima, which have been postulated to be the natively folded state where intramolecular interactions dominate, and the amyloid state where intermolecular interactions dominate. However, this view largely neglects the rich polymorphism found within amyloid species. We review the protein folding energy landscape in view of recent findings identifying specific transition routes among different amyloid polymorphs. Observed transitions such as twisted ribbon→crystal or helical ribbon→nanotube, and forbidden transitions such helical ribbon↛crystal, are discussed and positioned within the protein folding and aggregation energy landscape. Finally, amyloid crystals are identified as the ground state of the protein folding and aggregation energy landscape. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Polar firn air reveals large-scale impact of anthropogenic mercury emissions during the 1970s.

PubMed

Faïn, Xavier; Ferrari, Christophe P; Dommergue, Aurélien; Albert, Mary R; Battle, Mark; Severinghaus, Jeff; Arnaud, Laurent; Barnola, Jean-Marc; Cairns, Warren; Barbante, Carlo; Boutron, Claude

2009-09-22

Mercury (Hg) is an extremely toxic pollutant, and its biogeochemical cycle has been perturbed by anthropogenic emissions during recent centuries. In the atmosphere, gaseous elemental mercury (GEM; Hg degrees ) is the predominant form of mercury (up to 95%). Here we report the evolution of atmospheric levels of GEM in mid- to high-northern latitudes inferred from the interstitial air of firn (perennial snowpack) at Summit, Greenland. GEM concentrations increased rapidly after World War II from approximately 1.5 ng m(-3) reaching a maximum of approximately 3 ng m(-3) around 1970 and decreased until stabilizing at approximately 1.7 ng m(-3) around 1995. This reconstruction reproduces real-time measurements available from the Arctic since 1995 and exhibits the same general trend observed in Europe since 1990. Anthropogenic emissions caused a two-fold rise in boreal atmospheric GEM concentrations before the 1970s, which likely contributed to higher deposition of mercury in both industrialized and remotes areas. Once deposited, this toxin becomes available for methylation and, subsequently, the contamination of ecosystems. Implementation of air pollution regulations, however, enabled a large-scale decline in atmospheric mercury levels during the 1980s. The results shown here suggest that potential increases in emissions in the coming decades could have a similar large-scale impact on atmospheric Hg levels.

Generating scale-invariant perturbations from rapidly-evolving equation of state

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

Khoury, Justin; Steinhardt, Paul J.

2011-06-15

Recently, we introduced an ekpyrotic model based on a single, canonical scalar field that generates nearly scale-invariant curvature fluctuations through a purely ''adiabatic mechanism'' in which the background evolution is a dynamical attractor. Despite the starkly different physical mechanism for generating fluctuations, the two-point function is identical to inflation. In this paper, we further explore this concept, focusing in particular on issues of non-Gaussianity and quantum corrections. We find that the degeneracy with inflation is broken at three-point level: for the simplest case of an exponential potential, the three-point amplitude is strongly scale dependent, resulting in a breakdown of perturbationmore » theory on small scales. However, we show that the perturbative breakdown can be circumvented--and all issues raised in Linde et al. (arXiv:0912.0944) can be addressed--by altering the potential such that power is suppressed on small scales. The resulting range of nearly scale-invariant, Gaussian modes can be as much as 12 e-folds, enough to span the scales probed by microwave background and large-scale structure observations. On smaller scales, the spectrum is not scale invariant but is observationally acceptable.« less

A morphologic characterisation of the 1963 Vajont Slide, Italy, using long-range terrestrial photogrammetry

NASA Astrophysics Data System (ADS)

Wolter, Andrea; Stead, Doug; Clague, John J.

2014-02-01

The 1963 Vajont Slide in northeast Italy is an important engineering and geological event. Although the landslide has been extensively studied, new insights can be derived by applying modern techniques such as remote sensing and numerical modelling. This paper presents the first digital terrestrial photogrammetric analyses of the failure scar, landslide deposits, and the area surrounding the failure, with a focus on the scar. We processed photogrammetric models to produce discontinuity stereonets, residual maps and profiles, and slope and aspect maps, all of which provide information on the failure scar morphology. Our analyses enabled the creation of a preliminary semi-quantitative morphologic classification of the Vajont failure scar based on the large-scale tectonic folds and step-paths that define it. The analyses and morphologic classification have implications for the kinematics, dynamics, and mechanism of the slide. Metre- and decametre-scale features affected the initiation, direction, and displacement rate of sliding. The most complexly folded and stepped areas occur close to the intersection of orthogonal synclinal features related to the Dinaric and Neoalpine deformation events. Our analyses also highlight, for the first time, the evolution of the Vajont failure scar from 1963 to the present.

Examining diseased states in a scaled-up vocal fold model using simultaneous temporally resolved DPIV and pressure measurements

NASA Astrophysics Data System (ADS)

Rogers, Dylan; Wei, Nathaniel; Ringenber, Hunter; Krane, Michael; Wei, Timothy

2017-11-01

This study builds on the parallel presentation of Ringenberg, et al. (APS-DFD 2017) involving simultaneous, temporally and spatially resolved flow and pressure measurements in a scaled-up vocal fold model. In this talk, data from experiments replicating characteristics of diseased vocal folds are presented. This begins with vocal folds that do not fully close and continues with asymmetric oscillations. Data are compared to symmetric, i.e. `healthy', oscillatory motions presented in the companion talk. Having pressure and flow data for individual as well as phase averaged oscillations for these diseased cases highlights the potential for aeroacoustic analysis in this complex system. Supported by NIH Grant No. 2R01 DC005642-11.

Fast large-scale clustering of protein structures using Gauss integrals.

PubMed

Harder, Tim; Borg, Mikael; Boomsma, Wouter; Røgen, Peter; Hamelryck, Thomas

2012-02-15

Clustering protein structures is an important task in structural bioinformatics. De novo structure prediction, for example, often involves a clustering step for finding the best prediction. Other applications include assigning proteins to fold families and analyzing molecular dynamics trajectories. We present Pleiades, a novel approach to clustering protein structures with a rigorous mathematical underpinning. The method approximates clustering based on the root mean square deviation by first mapping structures to Gauss integral vectors--which were introduced by Røgen and co-workers--and subsequently performing K-means clustering. Compared to current methods, Pleiades dramatically improves on the time needed to perform clustering, and can cluster a significantly larger number of structures, while providing state-of-the-art results. The number of low energy structures generated in a typical folding study, which is in the order of 50,000 structures, can be clustered within seconds to minutes.

Dynamic Load Balancing for Adaptive Computations on Distributed-Memory Machines

NASA Technical Reports Server (NTRS)

1999-01-01

Dynamic load balancing is central to adaptive mesh-based computations on large-scale parallel computers. The principal investigator has investigated various issues on the dynamic load balancing problem under NASA JOVE and JAG rants. The major accomplishments of the project are two graph partitioning algorithms and a load balancing framework. The S-HARP dynamic graph partitioner is known to be the fastest among the known dynamic graph partitioners to date. It can partition a graph of over 100,000 vertices in 0.25 seconds on a 64- processor Cray T3E distributed-memory multiprocessor while maintaining the scalability of over 16-fold speedup. Other known and widely used dynamic graph partitioners take over a second or two while giving low scalability of a few fold speedup on 64 processors. These results have been published in journals and peer-reviewed flagship conferences.

Flexible, FEP-Teflon covered solar cell module development

NASA Technical Reports Server (NTRS)

Rauschenbach, H. S.; Cannady, M. D.

1976-01-01

Techniques and equipment were developed for the large scale, low-cost fabrication of lightweight, roll-up and fold-up, FEP-Teflon encapsulated solar cell modules. Modules were fabricated by interconnecting solderless single-crystal silicon solar cells and heat laminating them at approximately 300 C between layers of optically clear FEP and to a loadbearing Kapton substrate sheet. Modules were fabricated from both conventional and wraparound contact solar cells. A heat seal technique was developed for mechanically interconnecting modules into an array. The electrical interconnections for both roll-up and fold-up arrays were also developed. The use of parallel-gap resistance welding, ultrasonic bonding, and thermocompression bonding processes for attaching interconnects to solar cells were investigated. Parallel-gap welding was found to be best suited for interconnecting the solderless solar cells into modules. Details of the fabrication equipment, fabrication processes, module and interconnect designs, environmental test equipment, and test results are presented.

The bifurcations of nearly flat origami

NASA Astrophysics Data System (ADS)

Santangelo, Christian

Self-folding origami structures provide one means of fabricating complex, three-dimensional structures from a flat, two-dimensional sheet. Self-folding origami structures have been fabricated on scales ranging from macroscopic to microscopic and can have quite complicated structures with hundreds of folds arranged in complex patterns. I will describe our efforts to understand the mechanics and energetics of self-folding origami structures. Though the dimension of the configuration space of an origami structure scales with the size of the boundary and not with the number of vertices in the interior of the structure, a typical origami structure is also floppy in the sense that there are many possible ways to assign fold angles consistently. I will discuss our theoretical progress in understanding the geometry of the configuration space of origami. For random origami, the number of possible bifurcations grows surprisingly quickly even when the dimension of the configuration space is small. EFRI ODISSEI-1240441, DMR-0846582.

One Peptide Reveals the Two Faces of α-Helix Unfolding-Folding Dynamics.

PubMed

Jesus, Catarina S H; Cruz, Pedro F; Arnaut, Luis G; Brito, Rui M M; Serpa, Carlos

2018-04-12

The understanding of fast folding dynamics of single α-helices comes mostly from studies on rationally designed peptides displaying sequences with high helical propensity. The folding/unfolding dynamics and energetics of α-helix conformations in naturally occurring peptides remains largely unexplored. Here we report the study of a protein fragment analogue of the C-peptide from bovine pancreatic ribonuclease-A, RN80, a 13-amino acid residue peptide that adopts a highly populated helical conformation in aqueous solution. 1 H NMR and CD structural studies of RN80 showed that α-helix formation displays a pH-dependent bell-shaped curve, with a maximum near pH 5, and a large decrease in helical content in alkaline pH. The main forces stabilizing this short α-helix were identified as a salt bridge formed between Glu-2 and Arg-10 and the cation-π interaction involving Tyr-8 and His-12. Thus, deprotonation of Glu-2 or protonation of His-12 are essential for the RN80 α-helix stability. In the present study, RN80 folding and unfolding were triggered by laser-induced pH jumps and detected by time-resolved photoacoustic calorimetry (PAC). The photoacid proton release, amino acid residue protonation, and unfolding/folding events occur at different time scales and were clearly distinguished using time-resolved PAC. The partial unfolding of the RN80 α-helix, due to protonation of Glu-2 and consequent breaking of the stabilizing salt bridge between Glu-2 and Arg-10, is characterized by a concentration-independent volume expansion in the sub-microsecond time range (0.8 mL mol -1 , 369 ns). This small volume expansion reports the cost of peptide backbone rehydration upon disruption of a solvent-exposed salt bridge, as well as backbone intrinsic expansion. On the other hand, RN80 α-helix folding triggered by His-12 protonation and subsequent formation of a cation-π interaction leads to a microsecond volume contraction (-6.0 mL mol -1 , ∼1.7 μs). The essential role of two discrete side chain interactions, a salt bridge, and in particular a single cation-π interaction in the folding dynamics of a naturally occurring α-helix peptide is uniquely revealed by these data.

Replica Exchange with Solute Tempering: Efficiency in Large Scale Systems

PubMed Central

Huang, Xuhui; Hagen, Morten; Kim, Byungchan; Friesner, Richard A.; Zhou, Ruhong; Berne, B. J.

2009-01-01

We apply the recently developed replica exchange with solute tempering (REST) to three large solvated peptide systems: an α-helix, a β-hairpin, and a TrpCage, with these peptides defined as the “central group”. We find that our original implementation of REST is not always more efficient than the replica exchange method (REM). Specifically, we find that exchanges between folded (F) and unfolded (U) conformations with vastly different structural energies are greatly reduced by the nonappearance of the water self-interaction energy in the replica exchange acceptance probabilities. REST, however, is expected to remain useful for a large class of systems for which the energy gap between the two states is not large, such as weakly bound protein–ligand complexes. Alternatively, a shell of water molecules can be incorporated into the central group, as discussed in the original paper. PMID:17439169

Observations of Halley's Comet by the Solar Maximum Mission (SMM)

NASA Technical Reports Server (NTRS)

Niedner, M. B.

1986-01-01

Solar Maximum Mission coronagraph/polarimeter observations of large scale phenomena in Halley's Comet are discussed. Observations of the hydrogen coma with the UV spectrometer are considered. It is concluded that coronograph/polarimeter observations of the disconnection event, in which the entire plasma tail uproots itself from the head of the comet, is convected away in the solar wind at speeds in the 50 to 100 km/sec range (relative to the head), and is replaced by a plasma tail constructed from folding ion-tail rays, are the most interesting.

Balancing cross-sections combining field work and remote sensing data using LithoTect software in the Zagros fold-and-thrust belt, N Iraq.

NASA Astrophysics Data System (ADS)

Reif, Daniel; Grasemann, Bernhard; Lockhart, Duncan

2010-05-01

The Zagros fold-and-thrust belt has formed in detached Phanerozoic sedimentary cover rocks above a shortened crystalline Precambrian basement and evolved through the Late Cretaceous to Miocene collision between the Arabian and Eurasian plate, during which the Neotethys oceanic basin was closed. Deformation is partitioned in SW directed folding and thrusting of the sediments and NW-SE to N-S trending dextral strike slip faults. The sub-cylindrical doubly-plunging fold trains with wavelengths of 5 - 10 km host more than half of the world's hydrocarbon reserves in mostly anticlinal traps. Generally the Zagros is divided into three NW-SE striking tectonic units: the Zagros Imbricate Zone, the Zagros Simply Folded Belt and the Zagros Foredeep. This work presents a balanced cross-section through the Simply Folded Belt, NE of the city of Erbil (Kurdistan, Iraq). The regional stratigraphy comprises mainly Cretaceous to Cenozoic folded sediments consisting of massive, carbonate rocks (limestones, dolomites), reacting as competent layers during folding compared to the incompetent behavior of interlayered siltstones, claystones and marls. Although the overall security situation in Kurdistan is much better than in the rest of Iraq, structural field mapping was restricted to asphalt streets, mainly because of the contamination of the area with landmines and unexploded ordnance. In order to extend the structural measurements statistically over the investigated area, we used a newly developed software tool (www.terramath.com) for interactive structural mapping of spatial orientations (i.e. dip direction and dip angles) of the sedimentary beddings from digital elevation models. Structural field data and computed measurements where integrated and projected in NE-SW striking balanced cross-sections perpendicular to the regional trend of the fold axes. We used the software LithoTect (www.geologicsystems.com) for the restoration of the cross-sections. Depending on the interpretation of the shape of the synclines, which are not exposed and covered by Neogene sediments, the shortening is in the order of 10-20%. The restoration confirms that large scale faulting is only of minor importance in the Simply Folded Belt.

Flexural flow folding and the paleomagnetic fold test: An example of strain reorientation of remancence in the Mauch Chunk formation

NASA Astrophysics Data System (ADS)

Stamatakos, J.; Kodama, K. P.

1991-08-01

The relationship between the remanent magnetization and the detailed strain geometry around a first-order fold in the Appalachian Valley and Ridge Province was investigated to examine whether penetrative strains associated with folding can generate a apparent synfolding geometry from a prefolding magnetization. Paleomagnetic results from the Mississippian Mauch Chunk Formation on both limbs of the Frackville Anticline near Lavelle, Pennsylvania, yield two magnetic components, an intermediate unblocking temperature (300°C-600°C) Kiaman remagnetization and a two-polarity high unblocking temperature (650°C-680°C) characteristic magnetization. When the magnetic directions are incrementally corrected for bedding tilt, the intermediate-temperature component is most tightly clustered at 85% unfolding (D=176°, I=3°) and the high-temperature component is most tightly clustered at 75% unfolding (D=184°, I=27°). Mesoscopic and microscopic structural fabric analyses suggest a strain history that includes a significant component of flexural slip/flow folding. In the coarser-grained sandstone units, folding has largely been accommodated by slip on bedding, while in the finer-grained beds, folding has been accommodated by grain-scale deformation mechanisms such as pressure solution and low-temperature plasticity. Finite strain measurements, determined from center-to-center distances between quartz grains, yield strain ellipsoids consistent with this folding model. Inclination of the characteristic component varies as a function of the magnitude of the finite strain. This variation suggests that the characteristic magnetization has been systematically reoriented with respect to bedding during folding. Remanence directions on the south dipping limb have been rotated to shallower inclinations, while those on the north dipping limb have been rotated to steeper directions causing the prefolding magnetization to appear synfolding. These rotations are in agreement with models of rigid particle rotation in deforming viscous media. Unlike the characteristic magnetization, the secondary component appears to be unaffected by the deformation, and its synfolding behavior is interpreted as the acquisition of a secondary magnetization during Alleghenian folding. These results show that it is important to consider penetrative strains when evaluating the significance of apparent synfolding magnetizations.

Enhanced heat transfer is dependent on thickness of graphene films: the heat dissipation during boiling

PubMed Central

Ahn, Ho Seon; Kim, Jin Man; Kim, TaeJoo; Park, Su Cheong; Kim, Ji Min; Park, Youngjae; Yu, Dong In; Hwang, Kyoung Won; Jo, HangJin; Park, Hyun Sun; Kim, Hyungdae; Kim, Moo Hwan

2014-01-01

Boiling heat transfer (BHT) is a particularly efficient heat transport method because of the latent heat associated with the process. However, the efficiency of BHT decreases significantly with increasing wall temperature when the critical heat flux (CHF) is reached. Graphene has received much recent research attention for applications in thermal engineering due to its large thermal conductivity. In this study, graphene films of various thicknesses were deposited on a heated surface, and enhancements of BHT and CHF were investigated via pool-boiling experiments. In contrast to the well-known surface effects, including improved wettability and liquid spreading due to micron- and nanometer-scale structures, nanometer-scale folded edges of graphene films provided a clue of BHT improvement and only the thermal conductivity of the graphene layer could explain the dependence of the CHF on the thickness. The large thermal conductivity of the graphene films inhibited the formation of hot spots, thereby increasing the CHF. Finally, the provided empirical model could be suitable for prediction of CHF. PMID:25182076

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.

Cataract-associated P23T γD-crystallin retains a native-like fold in amorphous-looking aggregates formed at physiological pH

NASA Astrophysics Data System (ADS)

Boatz, Jennifer C.; Whitley, Matthew J.; Li, Mingyue; Gronenborn, Angela M.; van der Wel, Patrick C. A.

2017-05-01

Cataracts cause vision loss through the large-scale aggregation of eye lens proteins as a result of ageing or congenital mutations. The development of new treatments is hindered by uncertainty about the nature of the aggregates and their mechanism of formation. We describe the structure and morphology of aggregates formed by the P23T human γD-crystallin mutant associated with congenital cataracts. At physiological pH, the protein forms aggregates that look amorphous and disordered by electron microscopy, reminiscent of the reported formation of amorphous deposits by other crystallin mutants. Surprisingly, solid-state NMR reveals that these amorphous deposits have a high degree of structural homogeneity at the atomic level and that the aggregated protein retains a native-like conformation, with no evidence for large-scale misfolding. Non-physiological destabilizing conditions used in many in vitro aggregation studies are shown to yield qualitatively different, highly misfolded amyloid-like fibrils.

Solution-Processed Metal Coating to Nonwoven Fabrics for Wearable Rechargeable Batteries.

PubMed

Lee, Kyulin; Choi, Jin Hyeok; Lee, Hye Moon; Kim, Ki Jae; Choi, Jang Wook

2017-12-27

Wearable rechargeable batteries require electrode platforms that can withstand various physical motions, such as bending, folding, and twisting. To this end, conductive textiles and paper have been highlighted, as their porous structures can accommodate the stress built during various physical motions. However, fabrics with plain weaves or knit structures have been mostly adopted without exploration of nonwoven counterparts. Also, the integration of conductive materials, such as carbon or metal nanomaterials, to achieve sufficient conductivity as current collectors is not well-aligned with large-scale processing in terms of cost and quality control. Here, the superiority of nonwoven fabrics is reported in electrochemical performance and bending capability compared to currently dominant woven counterparts, due to smooth morphology near the fiber intersections and the homogeneous distribution of fibers. Moreover, solution-processed electroless deposition of aluminum and nickel-copper composite is adopted for cathodes and anodes, respectively, demonstrating the large-scale feasibility of conductive nonwoven platforms for wearable rechargeable batteries. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Reducing graphene device variability with yttrium sacrificial layers

NASA Astrophysics Data System (ADS)

Wang, Ning C.; Carrion, Enrique A.; Tung, Maryann C.; Pop, Eric

2017-05-01

Graphene technology has made great strides since the material was isolated more than a decade ago. However, despite improvements in growth quality and numerous "hero" devices, challenges of uniformity remain, restricting the large-scale development of graphene-based technologies. Here, we investigate and reduce the variability of graphene transistors by studying the effects of contact metals (with and without a Ti layer), resist, and yttrium (Y) sacrificial layers during the fabrication of hundreds of devices. We find that with optical photolithography, residual resist and process contamination are unavoidable, ultimately limiting the device performance and yield. However, using Y sacrificial layers to isolate the graphene from processing conditions improves the yield (from 73% to 97%), the average device performance (three-fold increase of mobility and 58% lower contact resistance), and the device-to-device variability (standard deviation of Dirac voltage reduced by 20%). In contrast to other sacrificial layer techniques, the removal of the Y sacrificial layer with dilute HCl does not harm surrounding materials, simplifying large-scale graphene fabrication.

Asymmetric vibration in a two-layer vocal fold model with left-right stiffness asymmetry: Experiment and simulation

PubMed Central

Zhang, Zhaoyan; Hieu Luu, Trung

2012-01-01

Vibration characteristics of a self-oscillating two-layer vocal fold model with left-right asymmetry in body-layer stiffness were experimentally and numerically investigated. Two regimes of distinct vibratory pattern were identified as a function of left-right stiffness mismatch. In the first regime with extremely large left-right stiffness mismatch, phonation onset resulted from an eigenmode synchronization process that involved only eigenmodes of the soft fold. Vocal fold vibration in this regime was dominated by a large-amplitude vibration of the soft fold, and phonation frequency was determined by the properties of the soft fold alone. The stiff fold was only enslaved to vibrate at a much reduced amplitude. In the second regime with small left-right stiffness mismatch, eigenmodes of both folds actively participated in the eigenmode synchronization process. The two folds vibrated with comparable amplitude, but the stiff fold consistently led the soft fold in phase for all conditions. A qualitatively good agreement was obtained between experiment and simulation, although the simulations generally underestimated phonation threshold pressure and onset frequency. The clinical implications of the results of this study are also discussed. PMID:22978891

Asymmetric vibration in a two-layer vocal fold model with left-right stiffness asymmetry: experiment and simulation.

PubMed

Zhang, Zhaoyan; Luu, Trung Hieu

2012-09-01

Vibration characteristics of a self-oscillating two-layer vocal fold model with left-right asymmetry in body-layer stiffness were experimentally and numerically investigated. Two regimes of distinct vibratory pattern were identified as a function of left-right stiffness mismatch. In the first regime with extremely large left-right stiffness mismatch, phonation onset resulted from an eigenmode synchronization process that involved only eigenmodes of the soft fold. Vocal fold vibration in this regime was dominated by a large-amplitude vibration of the soft fold, and phonation frequency was determined by the properties of the soft fold alone. The stiff fold was only enslaved to vibrate at a much reduced amplitude. In the second regime with small left-right stiffness mismatch, eigenmodes of both folds actively participated in the eigenmode synchronization process. The two folds vibrated with comparable amplitude, but the stiff fold consistently led the soft fold in phase for all conditions. A qualitatively good agreement was obtained between experiment and simulation, although the simulations generally underestimated phonation threshold pressure and onset frequency. The clinical implications of the results of this study are also discussed.

FOLD-EM: automated fold recognition in medium- and low-resolution (4-15 Å) electron density maps.

PubMed

Saha, Mitul; Morais, Marc C

2012-12-15

Owing to the size and complexity of large multi-component biological assemblies, the most tractable approach to determining their atomic structure is often to fit high-resolution radiographic or nuclear magnetic resonance structures of isolated components into lower resolution electron density maps of the larger assembly obtained using cryo-electron microscopy (cryo-EM). This hybrid approach to structure determination requires that an atomic resolution structure of each component, or a suitable homolog, is available. If neither is available, then the amount of structural information regarding that component is limited by the resolution of the cryo-EM map. However, even if a suitable homolog cannot be identified using sequence analysis, a search for structural homologs should still be performed because structural homology often persists throughout evolution even when sequence homology is undetectable, As macromolecules can often be described as a collection of independently folded domains, one way of searching for structural homologs would be to systematically fit representative domain structures from a protein domain database into the medium/low resolution cryo-EM map and return the best fits. Taken together, the best fitting non-overlapping structures would constitute a 'mosaic' backbone model of the assembly that could aid map interpretation and illuminate biological function. Using the computational principles of the Scale-Invariant Feature Transform (SIFT), we have developed FOLD-EM-a computational tool that can identify folded macromolecular domains in medium to low resolution (4-15 Å) electron density maps and return a model of the constituent polypeptides in a fully automated fashion. As a by-product, FOLD-EM can also do flexible multi-domain fitting that may provide insight into conformational changes that occur in macromolecular assemblies.

Lipid-protein nanodiscs promote in vitro folding of transmembrane domains of multi-helical and multimeric membrane proteins.

PubMed

Shenkarev, Zakhar O; Lyukmanova, Ekaterina N; Butenko, Ivan O; Petrovskaya, Lada E; Paramonov, Alexander S; Shulepko, Mikhail A; Nekrasova, Oksana V; Kirpichnikov, Mikhail P; Arseniev, Alexander S

2013-02-01

Production of helical integral membrane proteins (IMPs) in a folded state is a necessary prerequisite for their functional and structural studies. In many cases large-scale expression of IMPs in cell-based and cell-free systems results in misfolded proteins, which should be refolded in vitro. Here using examples of the bacteriorhodopsin ESR from Exiguobacterium sibiricum and full-length homotetrameric K(+) channel KcsA from Streptomyces lividans we found that the efficient in vitro folding of the transmembrane domains of the polytopic and multimeric IMPs could be achieved during the protein encapsulation into the reconstructed high-density lipoprotein particles, also known as lipid-protein nanodiscs. In this case the self-assembly of the IMP/nanodisc complexes from a mixture containing apolipoprotein, lipids and the partially denatured protein solubilized in a harsh detergent induces the folding of the transmembrane domains. The obtained folding yields showed significant dependence on the properties of lipids used for nanodisc formation. The largest recovery of the spectroscopically active ESR (~60%) from the sodium dodecyl sulfate (SDS) was achieved in the nanodiscs containing anionic saturated lipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPG) and was approximately twice lower in the zwitterionic DMPC lipid. The reassembly of tetrameric KcsA from the acid-dissociated monomer solubilized in SDS was the most efficient (~80%) in the nanodiscs containing zwitterionic unsaturated lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). The charged and saturated lipids provided lower tetramer quantities, and the lowest yield (<20%) was observed in DMPC. The overall yield of the ESR and KcsA folding was mainly restricted by the efficiency of the protein encapsulation into the nanodiscs. Copyright © 2012 Elsevier B.V. All rights reserved.

Recent trends in the frequency and duration of global floods

NASA Astrophysics Data System (ADS)

Najibi, Nasser; Devineni, Naresh

2018-06-01

Frequency and duration of floods are analyzed using the global flood database of the Dartmouth Flood Observatory (DFO) to explore evidence of trends during 1985-2015 at global and latitudinal scales. Three classes of flood duration (i.e., short: 1-7, moderate: 8-20, and long: 21 days and above) are also considered for this analysis. The nonparametric Mann-Kendall trend analysis is used to evaluate three hypotheses addressing potential monotonic trends in the frequency of flood, moments of duration, and frequency of specific flood duration types. We also evaluated if trends could be related to large-scale atmospheric teleconnections using a generalized linear model framework. Results show that flood frequency and the tails of the flood duration (long duration) have increased at both the global and the latitudinal scales. In the tropics, floods have increased 4-fold since the 2000s. This increase is 2.5-fold in the north midlatitudes. However, much of the trend in frequency and duration of the floods can be placed within the long-term climate variability context since the Atlantic Multidecadal Oscillation, North Atlantic Oscillation, and Pacific Decadal Oscillation were the main atmospheric teleconnections explaining this trend. There is no monotonic trend in the frequency of short-duration floods across all the global and latitudinal scales. There is a significant increasing trend in the annual median of flood durations globally and each latitudinal belt, and this trend is not related to these teleconnections. While the DFO data come with a certain level of epistemic uncertainty due to imprecision in the estimation of floods, overall, the analysis provides insights for understanding the frequency and persistence in hydrologic extremes and how they relate to changes in the climate, organization of global and local dynamical systems, and country-scale socioeconomic factors.

Hydrophobic Collapse of Ubiquitin Generates Rapid Protein-Water Motions.

PubMed

Wirtz, Hanna; Schäfer, Sarah; Hoberg, Claudius; Reid, Korey M; Leitner, David M; Havenith, Martina

2018-06-04

We report time-resolved measurements of the coupled protein-water modes of solvated ubiquitin during protein folding. Kinetic terahertz absorption (KITA) spectroscopy serves as a label-free technique for monitoring large scale conformational changes and folding of proteins subsequent to a sudden T-jump. We report here KITA measurements at an unprecedented time resolution of 500 ns, a resolution 2 orders of magnitude better than those of any previous KITA measurements, which reveal the coupled ubiquitin-solvent dynamics even in the initial phase of hydrophobic collapse. Complementary equilibrium experiments and molecular simulations of ubiquitin solutions are performed to clarify non-equilibrium contributions and reveal the molecular picture upon a change in structure, respectively. On the basis of our results, we propose that in the case of ubiquitin a rapid (<500 ns) initial phase of the hydrophobic collapse from the elongated protein to a molten globule structure precedes secondary structure formation. We find that these very first steps, including large-amplitude changes within the unfolded manifold, are accompanied by a rapid (<500 ns) pronounced change of the coupled protein-solvent response. The KITA response upon secondary structure formation exhibits an opposite sign, which indicates a distinct effect on the solvent-exposed surface.

Rubber and gel origami: visco- and poro-elastic behavior of folded structures

NASA Astrophysics Data System (ADS)

Evans, Arthur; Bende, Nakul; Na, Junhee; Hayward, Ryan; Santangelo, Christian

2014-11-01

The Japanese art of origami is rapidly becoming a platform for material design, as researchers develop systematic methods to exploit the purely geometric rules that allow paper to folded without stretching. Since any thin sheet couples mechanics strongly to geometry, origami provides a natural template for generating length-scale independent structures from a variety of different materials. In this talk I discuss some of the implications of using polymeric sheets and shells over many length scales to create folded materials with tunable shapes and properties. These implications include visco-elastic snap-through transitions and poro-elastically driven micro origami. In each case, mechanical response, dynamics, and reversible folding is tuned through a combination of geometry and constitutive properties, demonstrating the efficacy of using origami principles for designing functional materials.

Detection-dependent kinetics as a probe of folding landscape microstructure.

PubMed

Yang, Wei Yuan; Gruebele, Martin

2004-06-30

The folding landscapes of polypeptides and proteins exhibit a hierarchy of local minima. The causes range from proline isomerization all the way down to microstructure in the free energy caused by residual frustration inherent in even the best 20 amino acid design. The corresponding time scales range from hours to submicroseconds. The smallest microstructures are difficult to detect. We have measured the folding/unfolding kinetics of the engineered trpzip2 peptide at different tryptophan fluorescence wavelengths, each yielding a different rate. Wavelength-dependent folding kinetics on 0.1-2 mus time scales show that different microstructures with a range of solvent exposure and local dynamics are populated. We estimate a lower limit for the roughness of the free energy surface based on the range of rates observed.

Magnetorotational Dynamo Action in the Shearing Box

NASA Astrophysics Data System (ADS)

Walker, Justin; Boldyrev, Stanislav

2017-10-01

Magnetic dynamo action caused by the magnetorotational instability is studied in the shearing-box approximation with no imposed net magnetic flux. Consistent with recent studies, the dynamo action is found to be sensitive to the aspect ratio of the box: it is much easier to obtain in tall boxes (stretched in the direction normal to the disk plane) than in long boxes (stretched in the radial direction). Our direct numerical simulations indicate that the dynamo is possible in both cases, given a large enough magnetic Reynolds number. To explain the relatively larger effort required to obtain the dynamo action in a long box, we propose that the turbulent eddies caused by the instability most efficiently fold and mix the magnetic field lines in the radial direction. As a result, in the long box the scale of the generated strong azimuthal (stream-wise directed) magnetic field is always comparable to the scale of the turbulent eddies. In contrast, in the tall box the azimuthal magnetic flux spreads in the vertical direction over a distance exceeding the scale of the turbulent eddies. As a result, different vertical sections of the tall box are permeated by large-scale nonzero azimuthal magnetic fluxes, facilitating the instability. NSF AGS-1261659, Vilas Associates Award, NSF-Teragrid Project TG-PHY110016.

Exploration of Uncharted Regions of the Protein Universe

PubMed Central

Jaroszewski, Lukasz; Li, Zhanwen; Krishna, S. Sri; Bakolitsa, Constantina; Wooley, John; Deacon, Ashley M.; Wilson, Ian A.; Godzik, Adam

2009-01-01

The genome projects have unearthed an enormous diversity of genes of unknown function that are still awaiting biological and biochemical characterization. These genes, as most others, can be grouped into families based on sequence similarity. The PFAM database currently contains over 2,200 such families, referred to as domains of unknown function (DUF). In a coordinated effort, the four large-scale centers of the NIH Protein Structure Initiative have determined the first three-dimensional structures for more than 250 of these DUF families. Analysis of the first 248 reveals that about two thirds of the DUF families likely represent very divergent branches of already known and well-characterized families, which allows hypotheses to be formulated about their biological function. The remainder can be formally categorized as new folds, although about one third of these show significant substructure similarity to previously characterized folds. These results infer that, despite the enormous increase in the number and the diversity of new genes being uncovered, the fold space of the proteins they encode is gradually becoming saturated. The previously unexplored sectors of the protein universe appear to be primarily shaped by extreme diversification of known protein families, which then enables organisms to evolve new functions and adapt to particular niches and habitats. Notwithstanding, these DUF families still constitute the richest source for discovery of the remaining protein folds and topologies. PMID:19787035

Folding of viscous sheets and filaments

NASA Astrophysics Data System (ADS)

Skorobogatiy, M.; Mahadevan, L.

2000-12-01

We consider the nonlinear folding behavior of a viscous filament or a sheet under the influence of an external force such as gravity. Everyday examples of this phenomenon are provided by the periodic folding of a sheet of honey as it impinges on toast, or the folding of a stream of shampoo as it falls on one's hand. To understand the evolution of a fold, we formulate and solve a free-boundary problem for the phenomenon, give scaling laws for the size of the folds and the frequency with which they are laid out, and verify these experimentally.

Accelerating Electrostatic Surface Potential Calculation with Multiscale Approximation on Graphics Processing Units

PubMed Central

Anandakrishnan, Ramu; Scogland, Tom R. W.; Fenley, Andrew T.; Gordon, John C.; Feng, Wu-chun; Onufriev, Alexey V.

2010-01-01

Tools that compute and visualize biomolecular electrostatic surface potential have been used extensively for studying biomolecular function. However, determining the surface potential for large biomolecules on a typical desktop computer can take days or longer using currently available tools and methods. Two commonly used techniques to speed up these types of electrostatic computations are approximations based on multi-scale coarse-graining and parallelization across multiple processors. This paper demonstrates that for the computation of electrostatic surface potential, these two techniques can be combined to deliver significantly greater speed-up than either one separately, something that is in general not always possible. Specifically, the electrostatic potential computation, using an analytical linearized Poisson Boltzmann (ALPB) method, is approximated using the hierarchical charge partitioning (HCP) multiscale method, and parallelized on an ATI Radeon 4870 graphical processing unit (GPU). The implementation delivers a combined 934-fold speed-up for a 476,040 atom viral capsid, compared to an equivalent non-parallel implementation on an Intel E6550 CPU without the approximation. This speed-up is significantly greater than the 42-fold speed-up for the HCP approximation alone or the 182-fold speed-up for the GPU alone. PMID:20452792

Genome-scale gene expression characteristics define the follicular initiation and developmental rules during folliculogenesis.

PubMed

Shi, Kerong; He, Feng; Yuan, Xuefeng; Zhao, Yaofeng; Deng, Xuemei; Hu, Xiaoxiang; Li, Ning

2013-08-01

The ovarian follicle supplies a unique dynamic system for gametes that ensures the propagation of the species. During folliculogenesis, the vast majority of the germ cells are lost or inactivated because of ovarian follicle atresia, resulting in diminished reproductive potency and potential infertility. Understanding the underlying molecular mechanism of folliculogenesis rules is essential. Primordial (P), preantral (M), and large antral (L) porcine follicles were used to reveal their genome-wide gene expression profiles. Results indicate that primordial follicles (P) process a diverse gene expression pattern compared to growing follicles (M and L). The 5,548 differentially expressed genes display a similar expression mode in M and L, with a correlation coefficient of 0.892. The number of regulated (both up and down) genes in M is more than that in L. Also, their regulation folds in M (2-364-fold) are much more acute than in L (2-75-fold). Differentially expressed gene groups with different regulation patterns in certain follicular stages are identified and presumed to be closely related following follicular developmental rules. Interestingly, functional annotation analysis revealed that these gene groups feature distinct biological processes or molecular functions. Moreover, representative candidate genes from these gene groups have had their RNA or protein expressions within follicles confirmed. Our study emphasized genome-scale gene expression characteristics, which provide novel entry points for understanding the folliculogenesis rules on the molecular level, such as follicular initiation, atresia, and dominance. Transcriptional regulatory circuitries in certain follicular stages are expected to be found among the identified differentially expressed gene groups.

Herbivory drives large-scale spatial variation in reef fish trophic interactions

PubMed Central

Longo, Guilherme O; Ferreira, Carlos Eduardo L; Floeter, Sergio R

2014-01-01

Trophic interactions play a critical role in the structure and function of ecosystems. Given the widespread loss of biodiversity due to anthropogenic activities, understanding how trophic interactions respond to natural gradients (e.g., abiotic conditions, species richness) through large-scale comparisons can provide a broader understanding of their importance in changing ecosystems and support informed conservation actions. We explored large-scale variation in reef fish trophic interactions, encompassing tropical and subtropical reefs with different abiotic conditions and trophic structure of reef fish community. Reef fish feeding pressure on the benthos was determined combining bite rates on the substrate and the individual biomass per unit of time and area, using video recordings in three sites between latitudes 17°S and 27°S on the Brazilian Coast. Total feeding pressure decreased 10-fold and the composition of functional groups and species shifted from the northern to the southernmost sites. Both patterns were driven by the decline in the feeding pressure of roving herbivores, particularly scrapers, while the feeding pressure of invertebrate feeders and omnivores remained similar. The differential contribution to the feeding pressure across trophic categories, with roving herbivores being more important in the northernmost and southeastern reefs, determined changes in the intensity and composition of fish feeding pressure on the benthos among sites. It also determined the distribution of trophic interactions across different trophic categories, altering the evenness of interactions. Feeding pressure was more evenly distributed at the southernmost than in the southeastern and northernmost sites, where it was dominated by few herbivores. Species and functional groups that performed higher feeding pressure than predicted by their biomass were identified as critical for their potential to remove benthic biomass. Fishing pressure unlikely drove the large-scale pattern; however, it affected the contribution of some groups on a local scale (e.g., large-bodied parrotfish) highlighting the need to incorporate critical functions into conservation strategies. PMID:25512851

Efficient conformational space exploration in ab initio protein folding simulation.

PubMed

Ullah, Ahammed; Ahmed, Nasif; Pappu, Subrata Dey; Shatabda, Swakkhar; Ullah, A Z M Dayem; Rahman, M Sohel

2015-08-01

Ab initio protein folding simulation largely depends on knowledge-based energy functions that are derived from known protein structures using statistical methods. These knowledge-based energy functions provide us with a good approximation of real protein energetics. However, these energy functions are not very informative for search algorithms and fail to distinguish the types of amino acid interactions that contribute largely to the energy function from those that do not. As a result, search algorithms frequently get trapped into the local minima. On the other hand, the hydrophobic-polar (HP) model considers hydrophobic interactions only. The simplified nature of HP energy function makes it limited only to a low-resolution model. In this paper, we present a strategy to derive a non-uniform scaled version of the real 20×20 pairwise energy function. The non-uniform scaling helps tackle the difficulty faced by a real energy function, whereas the integration of 20×20 pairwise information overcomes the limitations faced by the HP energy function. Here, we have applied a derived energy function with a genetic algorithm on discrete lattices. On a standard set of benchmark protein sequences, our approach significantly outperforms the state-of-the-art methods for similar models. Our approach has been able to explore regions of the conformational space which all the previous methods have failed to explore. Effectiveness of the derived energy function is presented by showing qualitative differences and similarities of the sampled structures to the native structures. Number of objective function evaluation in a single run of the algorithm is used as a comparison metric to demonstrate efficiency.

The parallel universe of RNA folding.

PubMed

Batey, R T; Doudna, J A

1998-05-01

How do large RNA molecules find their active conformations among a universe of possible structures? Two recent studies reveal that RNA folding is a rapid and ordered process, with surprising similarities to protein folding mechanisms.

Atomistic Picture for the Folding Pathway of a Hybrid-1 Type Human Telomeric DNA G-quadruplex

PubMed Central

Bian, Yunqiang; Tan, Cheng; Wang, Jun; Sheng, Yuebiao; Zhang, Jian; Wang, Wei

2014-01-01

In this work we studied the folding process of the hybrid-1 type human telomeric DNA G-quadruplex with solvent and ions explicitly modeled. Enabled by the powerful bias-exchange metadynamics and large-scale conventional molecular dynamic simulations, the free energy landscape of this G-DNA was obtained for the first time and four folding intermediates were identified, including a triplex and a basically formed quadruplex. The simulations also provided atomistic pictures for the structures and cation binding patterns of the intermediates. The results showed that the structure formation and cation binding are cooperative and mutually supporting each other. The syn/anti reorientation dynamics of the intermediates was also investigated. It was found that the nucleotides usually take correct syn/anti configurations when they form native and stable hydrogen bonds with the others, while fluctuating between two configurations when they do not. Misfolded intermediates with wrong syn/anti configurations were observed in the early intermediates but not in the later ones. Based on the simulations, we also discussed the roles of the non-native interactions. Besides, the formation process of the parallel conformation in the first two G-repeats and the associated reversal loop were studied. Based on the above results, we proposed a folding pathway for the hybrid-1 type G-quadruplex with atomistic details, which is new and more complete compared with previous ones. The knowledge gained for this type of G-DNA may provide a general insight for the folding of the other G-quadruplexes. PMID:24722458

High-Throughput Microbore UPLC-MS Metabolic Phenotyping of Urine for Large-Scale Epidemiology Studies.

PubMed

Gray, Nicola; Lewis, Matthew R; Plumb, Robert S; Wilson, Ian D; Nicholson, Jeremy K

2015-06-05

A new generation of metabolic phenotyping centers are being created to meet the increasing demands of personalized healthcare, and this has resulted in a major requirement for economical, high-throughput metabonomic analysis by liquid chromatography-mass spectrometry (LC-MS). Meeting these new demands represents an emerging bioanalytical problem that must be solved if metabolic phenotyping is to be successfully applied to large clinical and epidemiological sample sets. Ultraperformance (UP)LC-MS-based metabolic phenotyping, based on 2.1 mm i.d. LC columns, enables comprehensive metabolic phenotyping but, when employed for the analysis of thousands of samples, results in high solvent usage. The use of UPLC-MS employing 1 mm i.d. columns for metabolic phenotyping rather than the conventional 2.1 mm i.d. methodology shows that the resulting optimized microbore method provided equivalent or superior performance in terms of peak capacity, sensitivity, and robustness. On average, we also observed, when using the microbore scale separation, an increase in response of 2-3 fold over that obtained with the standard 2.1 mm scale method. When applied to the analysis of human urine, the 1 mm scale method showed no decline in performance over the course of 1000 analyses, illustrating that microbore UPLC-MS represents a viable alternative to conventional 2.1 mm i.d. formats for routine large-scale metabolic profiling studies while also resulting in a 75% reduction in solvent usage. The modest increase in sensitivity provided by this methodology also offers the potential to either reduce sample consumption or increase the number of metabolite features detected with confidence due to the increased signal-to-noise ratios obtained. Implementation of this miniaturized UPLC-MS method of metabolic phenotyping results in clear analytical, economic, and environmental benefits for large-scale metabolic profiling studies with similar or improved analytical performance compared to conventional UPLC-MS.

Protein Folding and Self-Organized Criticality

NASA Astrophysics Data System (ADS)

Bajracharya, Arun; Murray, Joelle

Proteins are known to fold into tertiary structures that determine their functionality in living organisms. However, the complex dynamics of protein folding and the way they consistently fold into the same structures is not fully understood. Self-organized criticality (SOC) has provided a framework for understanding complex systems in various systems (earthquakes, forest fires, financial markets, and epidemics) through scale invariance and the associated power law behavior. In this research, we use a simple hydrophobic-polar lattice-bound computational model to investigate self-organized criticality as a possible mechanism for generating complexity in protein folding.

A field-cancellation algorithm for constructing economical planar permanent magnet (PM) multipoles with large high-quality field apertures

NASA Astrophysics Data System (ADS)

Tatchyn, Roman

1997-05-01

In recent years studies have been initiated on a new class of multipole field generators consisting of cuboid planar permanent magnet (PM) pieces arranged in bi-planar arrays of 2-fold rotational symmetry(R. Tatchyn, "Planar Permanent Magnet Multipoles: for Particle Accelerator and Storage Ring Applications ," IEEE Trans. Mag. 30, 5050(1994).)(T. Cremer, R. Tatchyn, "Planar Permanent Magnet Multipoles: Measurements and Configurations," in Proceedings of the 1995 Particle Accelerator Conference, IEEE Catalog No. 95CH35843, paper FAQ-20.). These structures, first introduced for Free Electron Laser (FEL) applications(R. Tatchyn, "Selected applications of planar permanent magnet multipoles in FEL insertion device design," NIM A341, 449(1994).), are based on reducing the rotational symmetry of conventional N-pole field generators from N-fold to 2-fold. One consequence of this reduction is a large higher-multipole content in a planar PM multipole's field at distances relatively close to the structure's axis, making it generally unsuitable for applications requiring a large high-quality field aperture. In this paper we outline an economical field-cancellation algorithm that can substantially decrease the harmonic content of a planar PM's field without breaking its biplanar geometry or 2-fold rotational symmetry. This will enable planar PM multipoles to be employed in a broader range of applications than heretofore possible, in particular as distributed focusing elements installed in insertion device gaps on synchrotron storage rings. This accomplishment is expected to remove the conventional restriction of an insertion device's length to the scale of the local focusing beta, enabling short-period, small-gap undulators to be installed and operated as high-brightness sources on lower-energy storage rings(R. Tatchyn, P. Csonka, A. Toor, "Perspectives on micropole undulators in synchrotron radiation technology," Rev. Sci. Instrum. 60(7), 1796(1989).). Operation as ordinary focusing elements in storage ring magnetic lattices, as well as the performance of other high-quality multipole applications, should also becomes possible with the realization of the proposed structures.

Nanoscale Viscoelasticity of Extracellular Matrix Proteins in Soft Tissues: a Multiscale Approach

PubMed Central

Miri, Amir K.; Heris, Hossein K.; Mongeau, Luc; Javid, Farhad

2013-01-01

We propose that the bulk viscoelasticity of soft tissues results from two length-scale-dependent mechanisms: the time-dependent response of extracellular matrix proteins (ECM) at the nanometer scale and the biophysical interactions between the ECM solid structure and interstitial fluid at the micrometer scale. The latter was modeled using the poroelasticity theory with an assumption of free motion of the interstitial fluid within the porous ECM structure. Following a recent study (Heris, H.K., Miri, A.K., Tripathy, U., Barthelat, F., Mongeau, L., 2013. Journal of the Mechanical Behavior of Biomedical Materials), atomic force microscopy was used to perform creep loading and 50-nm sinusoidal oscillations on porcine vocal folds. The proposed model was calibrated by a finite element model to accurately predict the nanoscale viscoelastic moduli of ECM. A linear correlation was observed between the in-depth distribution of the viscoelastic moduli and that of hyaluronic acids in the vocal fold tissue. We conclude that hyaluronic acids may regulate the vocal fold viscoelasticity at nanoscale. The proposed methodology offers a characterization tool for biomaterials used in vocal fold augmentations. PMID:24317493

Scalable cultivation of human pluripotent stem cells on chemically-defined surfaces

NASA Astrophysics Data System (ADS)

Hsiung, Michael Chi-Wei

Human stem cells (SCs) are classified as self-renewing cells possessing great ability in therapeutic applications due of their ability to differentiate along any major cell lineage in the human body. Despite their restorative potential, widespread use of SCs is hampered by strenuous control issues. Along with the need for strict xeno-free environments to sustain growth in culture, current methods for growing human pluripotent stem cells (hPSCs) rely on platforms which impede large-scale cultivation and therapeutic delivery. Hence, any progress towards development of large-scale culture systems is severely hindered. In a concentrated effort to develop a scheme that can serve as a model precursor for large scale SC propagation in clinical use, we have explored methods for cultivating hPSCs on completely defined surfaces. We discuss novel approaches with the potential to go beyond the limitations presented by current methods. In particular, we studied the cultivation of human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) on surface which underwent synthetic or chemical modification. Current methods for hPSCs rely on animal-based extracellular matrices (ECMs) such as mouse embryonic fibroblasts (MEFs) or feeders and murine sacoma cell-derived substrates to facilitate their growth. While these layers or coatings can be used to maximize the output of hPSC production, they cannot be considered for clinical use because they risk introducing foreign pathogens into culture. We have identified and developed conditions for a completely defined xeno-free substrate used for culturing hPSCs. By utilizing coupling chemistry, we can functionalize ester groups on a given surface and conjugate synthetic peptides containing the arginine-glycine-aspartic acid (RGD) motif, known for their role in cell adhesion. This method offers advantages over traditional hPSC culture by keeping the modified substrata free of xenogenic response and can be scaled up in adherent microcarrier culture. To treat a major organ such as the heart or kidney, producing large quantities of clinical-grade pluripotent cells is a necessity for cell-based therapy. Here we apply our approach to spherical beads or microcarriers for large-scale cultivation of hPSCs in a stirred-suspension bioreactor. Stem cells seeded on microcarriers and cultivated for multiple six day passages in a stirred-suspension bioreactors remained viable (≥90%) and increased by an average of 25.0+/-7.2-fold in concentration. The cells maintained their expression of pluripotency markers POU5F1 and NANOG as assessed by RT-PCR and quantitative PCR. These findings aim at the development of a flexible cost-effect method for the generation of pluripotent cells which can be repurposed and utilized for cell therapies. This work also aims to promote exploration into different methods of surface modification to develop new tactics for culturing hPSCs that can achieve higher fold growth while maintaining overall therapeutic potential.

A numerical study of the laminar necklace vortex system and its effect on the wake for a circular cylinder

NASA Astrophysics Data System (ADS)

Kirkil, Gokhan; Constantinescu, George

2014-11-01

Large Eddy Simulation is used to investigate the structure of the laminar horseshoe vortex (HV) system and the dynamics of the necklace vortices as they fold around the base of a circular cylinder mounted on the flat bed of an open channel for Reynolds numbers defined with the cylinder diameter, D, smaller than 4,460. The study concentrates on the analysis of the structure of the HV system in the periodic breakaway sub-regime which is characterized by the formation of three main necklace vortices. For the relatively shallow flow conditions considered in this study (H/D 1, H is the channel depth), at times, the disturbances induced by the legs of the necklace vortices do not allow the SSLs on the two sides of the cylinder to interact in a way that allows the vorticity redistribution mechanism to lead to the formation of a new wake roller. As a result, the shedding of large scale rollers in the turbulent wake is suppressed for relatively large periods of time. Simulation results show that the wake structure changes randomly between time intervals when large-scale rollers are forming and are convected in the wake (von Karman regime), and time intervals when the rollers do not form.

Dynamic behaviour of ice streams: the North East Greenland Ice Stream

NASA Astrophysics Data System (ADS)

Bons, Paul D.; Jansen, Daniela; Schaufler, Svenja; de Riese, Tamara; Sachau, Till; Weikusat, Ilka

2017-04-01

The flow of ice towards the margins of ice sheets is far from homogeneous. Ice streams show much higher flow velocities than their surroundings and may extend, for example the North East Greenland Ice Stream (NEGIS), towards the centre of the sheet. The elevated flow velocity inside an ice stream causes marginal shearing and convergent flow, which in turn leads to folding of ice layers. Such folding was documented in the Petermann Glacier in northern Greenland (Bons et al., 2016). 3-dimensional structural modelling using radargrams shows that folding is more intense adjacent to NEGIS than inside it, despite the strong flow perturbation at NEGIS. Analysis of fold amplitude as a function of stratigraphic level indicates that folding adjacent to NEGIS ceased in the early Holocene, while it is currently active inside NEGIS. The presence of folds adjacent of NEGIS, but also at other sites far in the interior of the Greenland Ice Sheet with no direct connection to the present-day surface velocity field, indicates that ice flow is not only heterogeneous in space (as the present-day flow velocity field shows), but also in time. The observations suggest that ice streams are dynamic, ephemeral structures that emerge and die out, and may possibly shift during their existence, but leave traces within the stratigraphic layering of the ice. The dynamic nature of ice streams such as NEGIS speaks against deterministic models for their accelerated flow rates, such as bedrock topography or thermal perturbations at their base. Instead, we suggest that ice streams can also result from strain localisation induced inside the ice sheet by the complex coupling of rheology, anisotropy, grain-size changes and possibly shear heating. Bons, P.D., Jansen, D., Mundel, F., Bauer, C.C., Binder, T., Eisen, O., Jessell, M.W., Llorens, M.-G, Steinbach, F., Steinhage, D. & Weikusat, I. 2016. Converging flow and anisotropy cause large-scale folding in Greenland's ice sheet. Nature Communications 7:11427, DOI: 10.1038/ncomms11427.

The influence of material anisotropy on vibration at onset in a three-dimensional vocal fold model

PubMed Central

Zhang, Zhaoyan

2014-01-01

Although vocal folds are known to be anisotropic, the influence of material anisotropy on vocal fold vibration remains largely unknown. Using a linear stability analysis, phonation onset characteristics were investigated in a three-dimensional anisotropic vocal fold model. The results showed that isotropic models had a tendency to vibrate in a swing-like motion, with vibration primarily along the superior-inferior direction. Anterior-posterior (AP) out-of-phase motion was also observed and large vocal fold vibration was confined to the middle third region along the AP length. In contrast, increasing anisotropy or increasing AP-transverse stiffness ratio suppressed this swing-like motion and allowed the vocal fold to vibrate in a more wave-like motion with strong medial-lateral motion over the entire medial surface. Increasing anisotropy also suppressed the AP out-of-phase motion, allowing the vocal fold to vibrate in phase along the entire AP length. Results also showed that such improvement in vibration pattern was the most effective with large anisotropy in the cover layer alone. These numerical predictions were consistent with previous experimental observations using self-oscillating physical models. It was further hypothesized that these differences may facilitate complete glottal closure in finite-amplitude vibration of anisotropic models as observed in recent experiments. PMID:24606284

First-order control of syntectonic sedimentation on crustal-scale structure of mountain belts

NASA Astrophysics Data System (ADS)

Erdős, Zoltán.; Huismans, Ritske S.; van der Beek, Peter

2015-07-01

The first-order characteristics of collisional mountain belts and the potential feedback with surface processes are predicted by critical taper theory. While the feedback between erosion and mountain belt structure has been fairly extensively studied, less attention has been given to the potential role of synorogenic deposition. For thin-skinned fold-and-thrust belts, recent studies indicate a strong control of syntectonic deposition on structure, as sedimentation tends to stabilize the thin-skinned wedge. However, the factors controlling basement deformation below fold-and-thrust belts, as evident, for example, in the Zagros Mountains or in the Swiss Alps, remain largely unknown. Previous work has suggested that such variations in orogenic structure may be explained by the thermotectonic "age" of the deforming lithosphere and hence its rheology. Here we demonstrate that sediment loading of the foreland basin area provides an additional control and may explain the variable basement involvement in orogenic belts. When examining the role of sedimentation, we identify two end-members: (1) sediment-starved orogenic systems with thick-skinned basement deformation in an axial orogenic core and thin-skinned deformation in the bordering forelands and (2) sediment-loaded orogens with thick packages of synorogenic deposits, derived from the axial basement zone, deposited on the surrounding foreland fold-and-thrust belts, and characterized by basement deformation below the foreland. Using high-resolution thermomechanical models, we demonstrate a strong feedback between deposition and crustal-scale thick-skinned deformation. Our results show that the loading effects of syntectonic sediments lead to long crustal-scale thrust sheets beneath the orogenic foreland and explain the contrasting characteristics of sediment-starved and sediment-loaded orogens, showing for the first time how both thin- and thick-skinned crustal deformations are linked to sediment deposition in these orogenic systems. We show that the observed model behavior is consistent with observations from a number of natural orogenic systems.

Influence of Pre-Existing Structure on Sill Geometry in the San Rafael Volcanic Field, Central Utah

NASA Astrophysics Data System (ADS)

Ferwerda, B.; Wetmore, P. H.; Connor, C.; Kruse, S. E.; Kiyosugi, K.; Kiflu, H. G.

2011-12-01

Sills have been hypothesized to be formed at rigidity contrasts between layers or at the level of neutral buoyancy of the intruding magma body. Recent field observations of sills in the San Rafael Volcanic Field (SRVF) in central Utah conflict with both of these hypotheses, suggesting that something else may control the distribution of sills in the crust. This study examines the role pre-existing structure plays in determining the distribution and geometry of sills in the SRVF. Primarily, sills will be thickest in the hinge zone of synclines and thinnest towards the limbs. The SRVF consists of a series of dikes, conduits and sills intruded into the J-Kr strata of the western Colorado Plateau. The structure of the SRVF consists of a series of broad wavelength folds truncated by a major thrust fault as determined by a gravity profile across structure. There are several sill complexes in the area whose geometry and relationships with the host rock are unaccounted for by these hypotheses. At large scale, sills follow structural trends in the host rock. Sills are either oriented with regional dips, or follow the trends of folds in the area. One sill, in particular, intruded into a syncline and thins towards the limb of the fold. However, sills behave differently at smaller spatial scales. The smaller scale behavior is incongruent with sills forming at rigidity contrasts or at the level of neutral buoyancy. First, sills form tiered structures intruding at multiple stratigraphic levels within the field area, and in limited geographic extent. Geophysical surveys confirm tiered sill structures in the subsurface. Individual sills also change stratigraphic levels, sometimes, very abruptly, moving vertically up to 30 meters in short horizontal distances. Sills also form networks in anastomosing structures that cut across stratigraphy at varying angles. These observations suggest that neither the level of neutral buoyancy nor the rigidity contrasts between layers play a role in determining the distribution of sills in the crust. Broadly, sills follow pre-existing structure, but at smaller scales, sills behave drastically different, with little regard to bedding planes.

Polar firn air reveals large-scale impact of anthropogenic mercury emissions during the 1970s

PubMed Central

Faïn, Xavier; Ferrari, Christophe P.; Dommergue, Aurélien; Albert, Mary R.; Battle, Mark; Severinghaus, Jeff; Arnaud, Laurent; Barnola, Jean-Marc; Cairns, Warren; Barbante, Carlo; Boutron, Claude

2009-01-01

Mercury (Hg) is an extremely toxic pollutant, and its biogeochemical cycle has been perturbed by anthropogenic emissions during recent centuries. In the atmosphere, gaseous elemental mercury (GEM; Hg°) is the predominant form of mercury (up to 95%). Here we report the evolution of atmospheric levels of GEM in mid- to high-northern latitudes inferred from the interstitial air of firn (perennial snowpack) at Summit, Greenland. GEM concentrations increased rapidly after World War II from ≈1.5 ng m−3 reaching a maximum of ≈3 ng m−3 around 1970 and decreased until stabilizing at ≈1.7 ng m−3 around 1995. This reconstruction reproduces real-time measurements available from the Arctic since 1995 and exhibits the same general trend observed in Europe since 1990. Anthropogenic emissions caused a two-fold rise in boreal atmospheric GEM concentrations before the 1970s, which likely contributed to higher deposition of mercury in both industrialized and remotes areas. Once deposited, this toxin becomes available for methylation and, subsequently, the contamination of ecosystems. Implementation of air pollution regulations, however, enabled a large-scale decline in atmospheric mercury levels during the 1980s. The results shown here suggest that potential increases in emissions in the coming decades could have a similar large-scale impact on atmospheric Hg levels. PMID:19805267

Significant enhancement of magnetoresistance with the reduction of particle size in nanometer scale

PubMed Central

Das, Kalipada; Dasgupta, P.; Poddar, A.; Das, I.

2016-01-01

The Physics of materials with large magnetoresistance (MR), defined as the percentage change of electrical resistance with the application of external magnetic field, has been an active field of research for quite some times. In addition to the fundamental interest, large MR has widespread application that includes the field of magnetic field sensor technology. New materials with large MR is interesting. However it is more appealing to vast scientific community if a method describe to achieve many fold enhancement of MR of already known materials. Our study on several manganite samples [La1−xCaxMnO3 (x = 0.52, 0.54, 0.55)] illustrates the method of significant enhancement of MR with the reduction of the particle size in nanometer scale. Our experimentally observed results are explained by considering model consisted of a charge ordered antiferromagnetic core and a shell having short range ferromagnetic correlation between the uncompensated surface spins in nanoscale regime. The ferromagnetic fractions obtained theoretically in the nanoparticles has been shown to be in the good agreement with the experimental results. The method of several orders of magnitude improvement of the magnetoresistive property will have enormous potential for magnetic field sensor technology. PMID:26837285

Evaluation of hollow fiber culture for large-scale production of mouse embryonic stem cell-derived hematopoietic stem cells.

PubMed

Nakano, Yu; Iwanaga, Shinya; Mizumoto, Hiroshi; Kajiwara, Toshihisa

2018-03-03

Hematopoietic stem cells (HSCs) have the ability to differentiate into all types of blood cells and can be transplanted to treat blood disorders. However, it is difficult to obtain HSCs in large quantities because of the shortage of donors. Recent efforts have focused on acquiring HSCs by differentiation of pluripotent stem cells. As a conventional differentiation method of pluripotent stem cells, the formation of embryoid bodies (EBs) is often employed. However, the size of EBs is limited by depletion of oxygen and nutrients, which prevents them from being efficient for the production of HSCs. In this study, we developed a large-scale hematopoietic differentiation approach for mouse embryonic stem (ES) cells by applying a hollow fiber (HF)/organoid culture method. Cylindrical organoids, which had the potential for further spontaneous differentiation, were established inside of hollow fibers. Using this method, we improved the proliferation rate of mouse ES cells to produce an increased HSC population and achieved around a 40-fold higher production volume of HSCs in HF culture than in conventional EB culture. Therefore, the HF/organoid culture method may be a new mass culture method to acquire pluripotent stem cell-derived HSCs.

Late Mesozoic tectonics of the Southern-Thai Peninsula: from transpression to basins opening

NASA Astrophysics Data System (ADS)

Sautter, Benjamin; Pubellier, Manuel; Menier, David

2015-04-01

The petroleum basins of the Southern Thailand Peninsula are poorly known and their final geometry is controlled by the Tertiary stress variations applied on pre-existing Paleozoic and Mesozoic basement structures. From the end of Mesozoic times, the arrival of Indian plate was accomodated by transpressionnal deformation along the Western Margin of Sunda Plate. Evidences of this strain are the motions along several regional strike Slip Faults (Sagaing, Three Pagodas, Mae Ping, Red River, Ranong and Klong Marui Faults) as well as compressional features (folds and thrusts) evidenced onshore. Due to changes in the boundary forces, these structures were reactivated during the Tertiary, leading to the opening of basins in this part of Sundaland. We present a structural analysis based on geomorphology, fieldwork and seismic interpretation of the Southern Thai Peninsula with emphasis on the deformation's style onshore from Ranong to Satun and offshore from Eastern Mergui to Songhkla. By analyzing morphostructures and drainage anomalies from Digital Elevation Model (SRTM and ASTER), we highlight a predominance of N-S structures in the Southern Thai Peninsula: both in the granitic belt and in the sedimentary cover. The Triassic-Jurassic (Indosinian) post-collision granitic belt is intensely fractured, with 2 penetrative directions: N140 and N50. On both sides, the sedimentary units appear folded at a large wavelength (~20km). On most of the studied outcrops, Triassic to Early Cretaceous series are gently tilted and weakly fractured whereas the Paleozoic ones shows intense fracturation and steep dipping beds. Moreover, all the Paleozoic stratas display a constant N-S S1 which does not appear in the Mezosoic sediments. Althought most of the post-Mesozoic sediments do not crop out due to thick vegetal cover, several Tertiary basins can be easily seen from seismic data both onshore and offshore. These data suggest that rifting started in the Eocene and was accommodated by large crust-scale Low Angle Normal Faults reactivating basement fabrics including intrusive edges and folds hinges. We propose a tectonic scenario for the southern Thai Peninsula according to which the northward motion of giant morphostructures (the Wharton Ridge followed by the Indian Plate) induced first right-lateral transpressionnal tectonics at the End of the Mesozoics. This system is illustrated by the 2 sets of fractures of the Indosinian Belt, the large-scale folds of Early Cretaceous Strata and the strike slip motions of the Ranong and Klong Marui Faults. Following the path of Indian Plate, a collapse of this hot and thin crust occurred accommodated via LANF's along the granitic belts and the sedimentary basement morpho-structures.

The pharmacokinetics of dexmedetomidine during long-term infusion in critically ill pediatric patients. A Bayesian approach with informative priors.

PubMed

Wiczling, Paweł; Bartkowska-Śniatkowska, Alicja; Szerkus, Oliwia; Siluk, Danuta; Rosada-Kurasińska, Jowita; Warzybok, Justyna; Borsuk, Agnieszka; Kaliszan, Roman; Grześkowiak, Edmund; Bienert, Agnieszka

2016-06-01

The purpose of this study was to assess the pharmacokinetics of dexmedetomidine in the ICU settings during the prolonged infusion and to compare it with the existing literature data using the Bayesian population modeling with literature-based informative priors. Thirty-eight patients were included in the analysis with concentration measurements obtained at two occasions: first from 0 to 24 h after infusion initiation and second from 0 to 8 h after infusion end. Data analysis was conducted using WinBUGS software. The prior information on dexmedetomidine pharmacokinetics was elicited from the literature study pooling results from a relatively large group of 95 children. A two compartment PK model, with allometrically scaled parameters, maturation of clearance and t-student residual distribution on a log-scale was used to describe the data. The incorporation of time-dependent (different between two occasions) PK parameters improved the model. It was observed that volume of distribution is 1.5-fold higher during the second occasion. There was also an evidence of increased (1.3-fold) clearance for the second occasion with posterior probability equal to 62 %. This work demonstrated the usefulness of Bayesian modeling with informative priors in analyzing pharmacokinetic data and comparing it with existing literature knowledge.

Anisotropic power spectrum and bispectrum in the f(Φ)F² mechanism

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

Bartolo, Nicola; Matarrese, Sabino; Peloso, Marco

2013-01-04

A suitable coupling of the inflaton φ to a vector kinetic term F² gives frozen and scale invariant vector perturbations. We compute the cosmological perturbations ζ that result from such coupling by taking into account the classical vector field that unavoidably gets generated at large scales during inflation. This generically results in a too-anisotropic power spectrum of ζ. Specifically, the anisotropy exceeds the 1% level (10% level) if inflation lasts ~5 e-folds (~50 e-folds) more than the minimal amount required to produce the cosmic microwave background modes. This conclusion applies, among others, to the application of this mechanism for magnetogenesis,more » for anisotropic inflation, and for the generation of anisotropic perturbations at the end of inflation through a waterfall field coupled to the vector (in this case, the unavoidable contribution that we obtain is effective all throughout inflation, and it is independent of the waterfall field). For a tuned duration of inflation, a 1% (10%) anisotropy in the power spectrum corresponds to an anisotropic bispectrum which is enhanced like the local one in the squeezed limit, and with an effective local f NL~3(~30). More in general, a significant anisotropy of the perturbations may be a natural outcome of all models that sustain higher than 0 spin fields during inflation.« less

Epitaxial Growth of Aligned and Continuous Carbon Nanofibers from Carbon Nanotubes.

PubMed

Lin, Xiaoyang; Zhao, Wei; Zhou, Wenbin; Liu, Peng; Luo, Shu; Wei, Haoming; Yang, Guangzhi; Yang, Junhe; Cui, Jie; Yu, Richeng; Zhang, Lina; Wang, Jiaping; Li, Qunqing; Zhou, Weiya; Zhao, Weisheng; Fan, Shoushan; Jiang, Kaili

2017-02-28

Exploiting the superior properties of nanomaterials at macroscopic scale is a key issue of nanoscience. Different from the integration strategy, "additive synthesis" of macroscopic structures from nanomaterial templates may be a promising choice. In this paper, we report the epitaxial growth of aligned, continuous, and catalyst-free carbon nanofiber thin films from carbon nanotube films. The fabrication process includes thickening of continuous carbon nanotube films by gas-phase pyrolytic carbon deposition and further graphitization of the carbon layer by high-temperature treatment. As-fabricated nanofibers in the film have an "annual ring" cross-section, with a carbon nanotube core and a graphitic periphery, indicating the templated growth mechanism. The absence of a distinct interface between the carbon nanotube template and the graphitic periphery further implies the epitaxial growth mechanism of the fiber. The mechanically robust thin film with tunable fiber diameters from tens of nanometers to several micrometers possesses low density, high electrical conductivity, and high thermal conductivity. Further extension of this fabrication method to enhance carbon nanotube yarns is also demonstrated, resulting in yarns with ∼4-fold increased tensile strength and ∼10-fold increased Young's modulus. The aligned and continuous features of the films together with their outstanding physical and chemical properties would certainly promote the large-scale applications of carbon nanofibers.

Anisotropic power spectrum and bispectrum in the f(ϕ)F2 mechanism

NASA Astrophysics Data System (ADS)

Bartolo, Nicola; Matarrese, Sabino; Peloso, Marco; Ricciardone, Angelo

2013-01-01

A suitable coupling of the inflaton φ to a vector kinetic term F2 gives frozen and scale invariant vector perturbations. We compute the cosmological perturbations ζ that result from such coupling by taking into account the classical vector field that unavoidably gets generated at large scales during inflation. This generically results in a too-anisotropic power spectrum of ζ. Specifically, the anisotropy exceeds the 1% level (10% level) if inflation lasts ˜5 e-folds (˜50 e-folds) more than the minimal amount required to produce the cosmic microwave background modes. This conclusion applies, among others, to the application of this mechanism for magnetogenesis, for anisotropic inflation, and for the generation of anisotropic perturbations at the end of inflation through a waterfall field coupled to the vector (in this case, the unavoidable contribution that we obtain is effective all throughout inflation, and it is independent of the waterfall field). For a tuned duration of inflation, a 1% (10%) anisotropy in the power spectrum corresponds to an anisotropic bispectrum which is enhanced like the local one in the squeezed limit, and with an effective local fNL˜3(˜30). More in general, a significant anisotropy of the perturbations may be a natural outcome of all models that sustain higher than 0 spin fields during inflation.

Influence of lithological heterogeneity, mechanical anisotropy, and magmatism on the rheology of an arc, North Cascades, Washington

NASA Astrophysics Data System (ADS)

Miller, Robert B.; Paterson, Scott R.

2001-12-01

Many aspects of crustal dynamics are dependent on changes in rheology and strength with depth in the lithosphere. Several of the controlling factors for rheology are difficult to study experimentally, particularly lithological heterogeneity, mechanical anisotropy, and magmatism, and we focus on these in a study of the deformation patterns in a thick crustal section (˜5- to 40-km paleodepth) through the Cretaceous Cascades core of the NW Cordillera. This magmatic arc consists of metamorphosed oceanic and arc terranes intruded by magmatic bodies ranging from <10-cm-thick sheets to large plutons. Heterogeneous brittle deformation marked by serpentinite melange characterizes the shallowest part of the crustal section, and the remainder of the section is characterized by heterogeneous, fold-dominated ductile deformation. Early tight to isoclinal recumbent folds and associated axial-planar fabrics are refolded by one or more cycles of nearly coaxial, open to isoclinal, upright to overturned folds. Layering played a mechanically active role during folding at all levels, as indicated by cleavage refraction, boudinaged layers, and kinematic indicators that record fold-related shear. Ductile deformation intensifies in the narrow structural aureoles of plutons, and SW-directed, reverse shear was partitioned into some of the aureoles. The poor strain memory of these magmatic bodies makes it difficult to determine if deformation was focused in the pluton magma chambers before they reached the solidus, as commonly predicted. All of the plutons have magmatic foliations that at least in part reflect regional strains, and these foliations are strong in the deeper plutons. The thinner sheets acted as competent bodies during folding and boudinage, after they reached the solidus, but generally did not cause marked strain gradients in their hosts. A relative strength profile constructed for the Cascades crustal section shows an overall decrease in strength with depth for the ductile part of the arc that fits idealized strength profiles. However, in more detail relative strengths are markedly variable. Units were able to accumulate large ductile strains, but even small variations in the physical properties of interlayered rock types exerted a strong influence on deformation patterns throughout the mid- to deep-crustal part of the profile. This profile thus emphasizes the complex vertical rheological stratification of arcs at the crustal to thin section scale, and should be applicable to many other magmatic arcs.

Wrinkle ridges on Venusian plains: Indicators of shallow crustal stress orientations at local and regional scales

NASA Technical Reports Server (NTRS)

Mcgill, George E.

1992-01-01

The plains regions of Venus exhibit a complex array of structural features, including deformation belts of various types, wrinkle ridges, grabens, and enigmatic radar-bright linears. Probably the most pervasive of these structures are the wrinkle ridges, which appear to be morphologically identical to their counterparts on the Moon and Mars. Almost all workers agree that wrinkle ridges result from horizontal compressive stresses in the crust; they either are explained as flexural fold structures, or alternatively as scarps or folds related to reverse faults. Wrinkle ridges generally are narrow, have small amplitudes, and commonly are closely spaced as well, characteristics that imply a shallow crustal origin. If wrinkle ridges are due to horizontally directed compressive stresses in the shallow crust, as generally has been inferred, then the trends of these features provide a means to map both local and regional orientations of principal stresses in the uppermost part of the venusian crust: maximum compressive stress is normal to the ridges, minimum compressive stress is normal to the topographic surface, and thus the wrinkle ridge trends trace the orientation of the intermediate principal stress. Because there are few plains areas on Venus totally devoid of wrinkle ridges, it should be possible to establish a number of interesting relationships on a near-global scale by mapping the trends of wrinkle ridges wherever they occur. The present study is addressing three questions: (1) Do the trends of wrinkle ridges define domains that are large relative to the sizes of individual plains regions? If so, can these domains be related to large-scale topographic or geologic features? (2) Are regional trends of wrinkle ridges affected by local features such as coronae? If so, is it possible to determine the relative ages of the far-field and local stresses from detailed study of trend inheritance or superposition relationships? (3) What is the relationship between wrinkle ridges and the larger ridges that make up ridge belts?

Rabbit biocontrol and landscape-scale recovery of threatened desert mammals.

PubMed

Pedler, Reece D; Brandle, Robert; Read, John L; Southgate, Richard; Bird, Peter; Moseby, Katherine E

2016-08-01

Funding for species conservation is insufficient to meet the current challenges facing global biodiversity, yet many programs use expensive single-species recovery actions and neglect broader management that addresses threatening processes. Arid Australia has the world's worst modern mammalian extinction record, largely attributable to competition from introduced herbivores, particularly European rabbits (Oryctolagus cuniculus) and predation by feral cats (Felis catus) and foxes (Vulpes vulpes). The biological control agent rabbit hemorrhagic disease virus (RHDV) was introduced to Australia in 1995 and resulted in dramatic, widespread rabbit suppression. We compared the area of occupancy and extent of occurrence of 4 extant species of small mammals before and after RHDV outbreak, relative to rainfall, sampling effort, and rabbit and predator populations. Despite low rainfall during the first 14 years after RHDV, 2 native rodents listed by the International Union for Conservation of Nature (IUCN), the dusky hopping-mouse (Notomys fuscus) and plains mouse (Pseudomys australis), increased their extent of occurrence by 241-365%. A threatened marsupial micropredator, the crest-tailed mulgara (Dasycercus cristicauda), underwent a 70-fold increase in extent of occurrence and a 20-fold increase in area of occupancy. Both bottom-up and top-down trophic effects were attributed to RHDV, namely decreased competition for food resources and declines in rabbit-dependent predators. Based on these sustained increases, these 3 previously threatened species now qualify for threat-category downgrading on the IUCN Red List. These recoveries are on a scale rarely documented in mammals and give impetus to programs aimed at targeted use of RHDV in Australia, rather than simply employing top-down threat-based management of arid ecosystems. Conservation programs that take big-picture approaches to addressing threatening processes over large spatial scales should be prioritized to maximize return from scarce conservation funding. Further, these should be coupled with long-term ecological monitoring, a critical tool in detecting and understanding complex ecosystem change. © 2016 Society for Conservation Biology.

Kinematic Model for the Sierra Nevada Frontal Fault Zone, California: Paleomagnetism of the Eureka Valley Tuff

NASA Astrophysics Data System (ADS)

Rood, D. H.; Burbank, D. W.; Luyendyk, B. P.

2005-12-01

We document the geometry, timing, rates, and kinematic style of Late Tertiary deformation between Sonora Pass and Mono Basin, central Sierra Nevada, California. Observed mismatches between geodetic and geologic deformation rates in the western Great Basin may be primarily due to underestimates of true geologic deformation. Relatively little attention has been paid to the role of permanent deformation between faults, i.e. folding or crustal block rotation. Current slip discrepancies may be accounted for if a significant component of off-fault transrotational deformation is present. We use geologic and paleomagnetic data to address the kinematic development of the Sierra Nevada frontal fault zone (SNFFZ), and to quantify both the elastic and inelastic strain accumulated across the Sierra Nevada-Basin and Range transition since ~9 Ma. The complex structure of this transition, between the regions of Sonora Pass and Mono Basin, may be a result of three distinct modes of dextral shear accommodation (transtensional, transpressional, and crustal thinning). The study area is characterized by four important structural elements that lie between the SNFFZ and Walker Lane Belt: (1) N- to NNW-striking normal and oblique faults, dominantly E-dipping, and associated W-tilted fault blocks; (2) NW-striking dextral faults; (3) ENE- to NE-striking left-lateral oblique faults that may accommodate overall dextral shear through clockwise vertical axis rotations of fault blocks; (4) E- to NE-trending folds, which may accommodate N-S shortening at large-scale left steps in the dextral transtensional fault system. Between Bridgeport and Mono Basins, a regional E- to NE-trending fold is present that affects both the Tertiary volcanic strata and a Quaternary glacial outwash surface. To the west, normal faulting rates on the SNFFZ are 1-2 mm/yr (Bursik and Sieh, 1989). This slip decreases to the north, into the folded region of the Bodie Hills. This kinematic relationship suggests that the region may be an accommodation zone between two linking faults, possibly an active fold that accommodates N-S shortening at a large-scale left step in the range front fault system. We collected ~200 paleomagnetic samples from the Late Miocene Eureka Valley Tuff of the Stanislaus Group at 21 sites over a 125-km-long, E-W transect (from the Sierra Nevada foothills to east of Mono Basin). Stepwise AF demagnetization reveals a stable characteristic remnant magnetization. Our preliminary data suggest 20-40 degrees of clockwise rotation adjacent to faults of the SNFFZ. An expanded dataset aims to identify specific structural domains, quantify differential vertical axis block rotations, and test geometric models of transrotation (i.e. block-specific versus gradational) during transtensional lithospheric deformation.

Physical and molecular bases of protein thermal stability and cold adaptation.

PubMed

Pucci, Fabrizio; Rooman, Marianne

2017-02-01

The molecular bases of thermal and cold stability and adaptation, which allow proteins to remain folded and functional in the temperature ranges in which their host organisms live and grow, are still only partially elucidated. Indeed, both experimental and computational studies fail to yield a fully precise and global physical picture, essentially because all effects are context-dependent and thus quite intricate to unravel. We present a snapshot of the current state of knowledge of this highly complex and challenging issue, whose resolution would enable large-scale rational protein design. Copyright © 2016 Elsevier Ltd. All rights reserved.

Scaling of data communications for an advanced supercomputer network

NASA Technical Reports Server (NTRS)

Levin, E.; Eaton, C. K.; Young, Bruce

1986-01-01

The goal of NASA's Numerical Aerodynamic Simulation (NAS) Program is to provide a powerful computational environment for advanced research and development in aeronautics and related disciplines. The present NAS system consists of a Cray 2 supercomputer connected by a data network to a large mass storage system, to sophisticated local graphics workstations and by remote communication to researchers throughout the United States. The program plan is to continue acquiring the most powerful supercomputers as they become available. The implications of a projected 20-fold increase in processing power on the data communications requirements are described.

Competing Pathways and Multiple Folding Nuclei in a Large Multidomain Protein, Luciferase.

PubMed

Scholl, Zackary N; Yang, Weitao; Marszalek, Piotr E

2017-05-09

Proteins obtain their final functional configuration through incremental folding with many intermediate steps in the folding pathway. If known, these intermediate steps could be valuable new targets for designing therapeutics and the sequence of events could elucidate the mechanism of refolding. However, determining these intermediate steps is hardly an easy feat, and has been elusive for most proteins, especially large, multidomain proteins. Here, we effectively map part of the folding pathway for the model large multidomain protein, Luciferase, by combining single-molecule force-spectroscopy experiments and coarse-grained simulation. Single-molecule refolding experiments reveal the initial nucleation of folding while simulations corroborate these stable core structures of Luciferase, and indicate the relative propensities for each to propagate to the final folded native state. Both experimental refolding and Monte Carlo simulations of Markov state models generated from simulation reveal that Luciferase most often folds along a pathway originating from the nucleation of the N-terminal domain, and that this pathway is the least likely to form nonnative structures. We then engineer truncated variants of Luciferase whose sequences corresponded to the putative structure from simulation and we use atomic force spectroscopy to determine their unfolding and stability. These experimental results corroborate the structures predicted from the folding simulation and strongly suggest that they are intermediates along the folding pathway. Taken together, our results suggest that initial Luciferase refolding occurs along a vectorial pathway and also suggest a mechanism that chaperones may exploit to prevent misfolding. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Consistent Large-Eddy Simulation of a Temporal Mixing Layer Laden with Evaporating Drops. Part 2; A Posteriori Modelling

NASA Technical Reports Server (NTRS)

Leboissertier, Anthony; Okong'O, Nora; Bellan, Josette

2005-01-01

Large-eddy simulation (LES) is conducted of a three-dimensional temporal mixing layer whose lower stream is initially laden with liquid drops which may evaporate during the simulation. The gas-phase equations are written in an Eulerian frame for two perfect gas species (carrier gas and vapour emanating from the drops), while the liquid-phase equations are written in a Lagrangian frame. The effect of drop evaporation on the gas phase is considered through mass, species, momentum and energy source terms. The drop evolution is modelled using physical drops, or using computational drops to represent the physical drops. Simulations are performed using various LES models previously assessed on a database obtained from direct numerical simulations (DNS). These LES models are for: (i) the subgrid-scale (SGS) fluxes and (ii) the filtered source terms (FSTs) based on computational drops. The LES, which are compared to filtered-and-coarsened (FC) DNS results at the coarser LES grid, are conducted with 64 times fewer grid points than the DNS, and up to 64 times fewer computational than physical drops. It is found that both constant-coefficient and dynamic Smagorinsky SGS-flux models, though numerically stable, are overly dissipative and damp generated small-resolved-scale (SRS) turbulent structures. Although the global growth and mixing predictions of LES using Smagorinsky models are in good agreement with the FC-DNS, the spatial distributions of the drops differ significantly. In contrast, the constant-coefficient scale-similarity model and the dynamic gradient model perform well in predicting most flow features, with the latter model having the advantage of not requiring a priori calibration of the model coefficient. The ability of the dynamic models to determine the model coefficient during LES is found to be essential since the constant-coefficient gradient model, although more accurate than the Smagorinsky model, is not consistently numerically stable despite using DNS-calibrated coefficients. With accurate SGS-flux models, namely scale-similarity and dynamic gradient, the FST model allows up to a 32-fold reduction in computational drops compared to the number of physical drops, without degradation of accuracy; a 64-fold reduction leads to a slight decrease in accuracy.

Development of laryngeal video stroboscope with laser marking module for dynamic glottis measurement.

PubMed

Kuo, Chung-Feng Jeffrey; Wang, Hsing-Won; Hsiao, Shang-Wun; Peng, Kai-Ching; Chou, Ying-Liang; Lai, Chun-Yu; Hsu, Chien-Tung Max

2014-01-01

Physicians clinically use laryngeal video stroboscope as an auxiliary instrument to test glottal diseases, and read vocal fold images and voice quality for diagnosis. As the position of vocal fold varies in each person, the proportion of the vocal fold size as presented in the vocal fold image is different, making it impossible to directly estimate relevant glottis physiological parameters, such as the length, area, perimeter, and opening angle of the glottis. Hence, this study designs an innovative laser projection marking module for the laryngeal video stroboscope to provide reference parameters for image scaling conversion. This innovative laser projection marking module to be installed on the laryngeal video stroboscope using laser beams to project onto the glottis plane, in order to provide reference parameters for scaling conversion of images of laryngeal video stroboscope. Copyright © 2013 Elsevier Ltd. All rights reserved.

Evolutionary conservation of codon optimality reveals hidden signatures of cotranslational folding.

PubMed

Pechmann, Sebastian; Frydman, Judith

2013-02-01

The choice of codons can influence local translation kinetics during protein synthesis. Whether codon preference is linked to cotranslational regulation of polypeptide folding remains unclear. Here, we derive a revised translational efficiency scale that incorporates the competition between tRNA supply and demand. Applying this scale to ten closely related yeast species, we uncover the evolutionary conservation of codon optimality in eukaryotes. This analysis reveals universal patterns of conserved optimal and nonoptimal codons, often in clusters, which associate with the secondary structure of the translated polypeptides independent of the levels of expression. Our analysis suggests an evolved function for codon optimality in regulating the rhythm of elongation to facilitate cotranslational polypeptide folding, beyond its previously proposed role of adapting to the cost of expression. These findings establish how mRNA sequences are generally under selection to optimize the cotranslational folding of corresponding polypeptides.

Terahertz circular dichroism spectroscopy of biomolecules

NASA Astrophysics Data System (ADS)

Xu, Jing; Galan, Jhenny; Ramian, Gerald; Savvidis, Pavlos; Scopatz, Anthony; Birge, Robert R.; Allen, S. James; Plaxco, Kevin

2004-02-01

Biopolymers such as proteins, DNA and RNA fold into large, macromolecular chiral structures. As charged macromolecules, they absorb strongly in the terahertz due to large-scale collective vibrational modes; as chiral objects, this absorption should be coupled with significant circular dichroism. Terahertz circular dichroism (TCD) is potentially important as a biospecific sensor, unobscured by spectral features related to abiological material. We have constructed atomistic simulations and elastic continuum models of TCD. These models estimate the magnitude of the TCD and the relation between TCD spectroscopic signatures (zero crossings) and the structure, charge distribution and mechanical properties of biomaterials. A broad band TCD spectrometer based on a polarizing interferometer is developed to explore TCD in biomolecules in aqueous solution. Preliminary results on TCD in lysozyme in water at several terahertz frequencies is presented.

Field and Laboratory Data From an Earthquake History Study of Scarps in the Hanging Wall of the Tacoma Fault, Mason and Pierce Counties, Washington

USGS Publications Warehouse

Nelson, Alan R.; Personius, Stephen F.; Sherrod, Brian L.; Buck, Jason; Bradley, Lee-Ann; Henley, Gary; Liberty, Lee M.; Kelsey, Harvey M.; Witter, Robert C.; Koehler, R.D.; Schermer, Elizabeth R.; Nemser, Eliza S.; Cladouhos, Trenton T.

2008-01-01

As part of the effort to assess seismic hazard in the Puget Sound region, we map fault scarps on Airborne Laser Swath Mapping (ALSM, an application of LiDAR) imagery (with 2.5-m elevation contours on 1:4,000-scale maps) and show field and laboratory data from backhoe trenches across the scarps that are being used to develop a latest Pleistocene and Holocene history of large earthquakes on the Tacoma fault. We supplement previous Tacoma fault paleoseismic studies with data from five trenches on the hanging wall of the fault. In a new trench across the Catfish Lake scarp, broad folding of more tightly folded glacial sediment does not predate 4.3 ka because detrital charcoal of this age was found in stream-channel sand in the trench beneath the crest of the scarp. A post-4.3-ka age for scarp folding is consistent with previously identified uplift across the fault during AD 770-1160. In the trench across the younger of the two Stansberry Lake scarps, six maximum 14C ages on detrital charcoal in pre-faulting B and C soil horizons and three minimum ages on a tree root in post-faulting colluvium, limit a single oblique-slip (right-lateral) surface faulting event to AD 410-990. Stratigraphy and sedimentary structures in the trench across the older scarp at the same site show eroded glacial sediments, probably cut by a meltwater channel, with no evidence of post-glacial deformation. At the northeast end of the Sunset Beach scarps, charcoal ages in two trenches across graben-forming scarps give a close maximum age of 1.3 ka for graben formation. The ages that best limit the time of faulting and folding in each of the trenches are consistent with the time of the large regional earthquake in southern Puget Sound about AD 900-930.

Bio-stimuli-responsive multi-scale hyaluronic acid nanoparticles for deepened tumor penetration and enhanced therapy.

PubMed

Huo, Mengmeng; Li, Wenyan; Chaudhuri, Arka Sen; Fan, Yuchao; Han, Xiu; Yang, Chen; Wu, Zhenghong; Qi, Xiaole

2017-09-01

In this study, we developed bio-stimuli-responsive multi-scale hyaluronic acid (HA) nanoparticles encapsulated with polyamidoamine (PAMAM) dendrimers as the subunits. These HA/PAMAM nanoparticles of large scale (197.10±3.00nm) were stable during systematic circulation then enriched at the tumor sites; however, they were prone to be degraded by the high expressed hyaluronidase (HAase) to release inner PAMAM dendrimers and regained a small scale (5.77±0.25nm) with positive charge. After employing tumor spheroids penetration assay on A549 3D tumor spheroids for 8h, the fluorescein isothiocyanate (FITC) labeled multi-scale HA/PAMAM-FITC nanoparticles could penetrate deeply into these tumor spheroids with the degradation of HAase. Moreover, small animal imaging technology in male nude mice bearing H22 tumor showed HA/PAMAM-FITC nanoparticles possess higher prolonged systematic circulation compared with both PAMAM-FITC nanoparticles and free FITC. In addition, after intravenous administration in mice bearing H22 tumors, methotrexate (MTX) loaded multi-scale HA/PAMAM-MTX nanoparticles exhibited a 2.68-fold greater antitumor activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Active transpression in the northern Calabria Apennines, southern Italy

NASA Astrophysics Data System (ADS)

Ferranti, L.; Santoro, E.; Mazzella, M. E.; Monaco, C.; Morelli, D.

2009-10-01

An integrated analysis of geomorphologic and structural data, offshore seismic profiles and local network seismicity, is used to shed light on the hitherto poorly known active deformation field that affects the Southern Apennines orogen in northern Calabria region. In the Southern Apennines, Middle Pleistocene waning of Miocene-Early Pleistocene thin-skinned frontal thrust belt motion toward the Apulian foreland to the NE was coeval to onset of regional uplift, which is documented by flights of raised marine terraces. Short-wavelength (˜ 5-10 km) and amplitude (˜ 20-50 m) undulations are superposed to the regional uplift (˜ 100 km length and ˜ 500 m amplitude scale) profile of Middle-Upper Pleistocene marine terraces on the Ionian Sea coast of northern Calabria stretching along the borders of the Sila and Pollino mountain ranges and across the intervening Sibari coastal plain. The secondary undulations spatially coincide with the last generation of ˜ W- to ˜ WNW-striking folds traced in bedrock and locally within Early to Middle Pleistocene continental to transitional deposits. The very recent activity of these structures is highlighted by a range of fluvial geomorphic anomalies and by involvement in folding and locally transpressional faulting of the Middle Pleistocene and younger depositional sequences submerged beneath the continental shelf. We argue that the local-scale, but pervasive undulations in the deformation profile of marine terraces represent shallow-crustal folds grown within a recent and still active transpressional field. A major structural culmination bound by fore- and retro-verging transpressional shear zones is represented by the Pollino mountain range and its offshore extension in the Amendolara ridge, and a further SW-directed transpressional belt is found in northern Sila and adjacent sea bottom. Epicenter distribution and focal solutions of low- to moderate crustal earthquakes illuminate the two NW-SE trending structural belts beneath the Amendolara ridge and northern Sila, where partitioning between thrust and left strike-slip motion occurs in response to ˜ E to ˜ NE directed shortening. A local ˜ NW-SE extension is recorded by fault-kinematic analysis on NE-SW striking fault segments parallel to the coast on the eastern flank of Pollino. These small-length normal faults do not form a through-going lineament, rather they accommodate the seaward collapse of the uppermost crust above the deeper shortening compartment. Conversely, the active transpression testified by geomorphic, structural and seismicity data is accommodated along deep-seated oblique back-thrusts that involve the Apulian foreland plate underlying the now inactive thin-skinned accretionary wedge down to near-Moho depths. In light of the tight interlacing between regional and local components of deformation affecting the marine terraces, we suggest that the large-scale uplift in this sector of Calabria may reflect whole crustal-scale folding. The novel seismotectonic frame reconstructed for this region is consistent with GPS velocities suggesting that large part of geodetic shortening detected between the Apennines and the Apulian block on the eastern side of southern Italy might be accommodated in northern Calabria.

Golf-course and funnel energy landscapes: Protein folding concepts in martensites

NASA Astrophysics Data System (ADS)

Shankaraiah, N.

2017-06-01

We use protein folding energy landscape concepts such as golf course and funnel to study re-equilibration in athermal martensites under systematic temperature quench Monte Carlo simulations. On quenching below a transition temperature, the seeded high-symmetry parent-phase austenite that converts to the low-symmetry product-phase martensite, through autocatalytic twinning or elastic photocopying, has both rapid conversions and incubation delays in the temperature-time-transformation phase diagram. We find the rapid (incubation delays) conversions at low (high) temperatures arises from the presence of large (small) size of golf-course edge that has the funnel inside for negative energy states. In the incubating state, the strain structure factor enters into the Brillouin-zone golf course through searches for finite transitional pathways which close off at the transition temperature with Vogel-Fulcher divergences that are insensitive to Hamiltonian energy scales and log-normal distributions, as signatures of dominant entropy barriers. The crossing of the entropy barrier is identified through energy occupancy distributions, Monte Carlo acceptance fractions, heat emission, and internal work.

Mutual Information between Discrete Variables with Many Categories using Recursive Adaptive Partitioning

PubMed Central

Seok, Junhee; Seon Kang, Yeong

2015-01-01

Mutual information, a general measure of the relatedness between two random variables, has been actively used in the analysis of biomedical data. The mutual information between two discrete variables is conventionally calculated by their joint probabilities estimated from the frequency of observed samples in each combination of variable categories. However, this conventional approach is no longer efficient for discrete variables with many categories, which can be easily found in large-scale biomedical data such as diagnosis codes, drug compounds, and genotypes. Here, we propose a method to provide stable estimations for the mutual information between discrete variables with many categories. Simulation studies showed that the proposed method reduced the estimation errors by 45 folds and improved the correlation coefficients with true values by 99 folds, compared with the conventional calculation of mutual information. The proposed method was also demonstrated through a case study for diagnostic data in electronic health records. This method is expected to be useful in the analysis of various biomedical data with discrete variables. PMID:26046461

Improvements in pollutant monitoring: optimizing silicone for co-deployment with polyethylene passive sampling devices.

PubMed

O'Connell, Steven G; McCartney, Melissa A; Paulik, L Blair; Allan, Sarah E; Tidwell, Lane G; Wilson, Glenn; Anderson, Kim A

2014-10-01

Sequestering semi-polar compounds can be difficult with low-density polyethylene (LDPE), but those pollutants may be more efficiently absorbed using silicone. In this work, optimized methods for cleaning, infusing reference standards, and polymer extraction are reported along with field comparisons of several silicone materials for polycyclic aromatic hydrocarbons (PAHs) and pesticides. In a final field demonstration, the most optimal silicone material is coupled with LDPE in a large-scale study to examine PAHs in addition to oxygenated-PAHs (OPAHs) at a Superfund site. OPAHs exemplify a sensitive range of chemical properties to compare polymers (log Kow 0.2-5.3), and transformation products of commonly studied parent PAHs. On average, while polymer concentrations differed nearly 7-fold, water-calculated values were more similar (about 3.5-fold or less) for both PAHs (17) and OPAHs (7). Individual water concentrations of OPAHs differed dramatically between silicone and LDPE, highlighting the advantages of choosing appropriate polymers and optimized methods for pollutant monitoring. Copyright © 2014 Elsevier Ltd. All rights reserved.

IMPROVEMENTS IN POLLUTANT MONITORING: OPTIMIZING SILICONE FOR CO-DEPLOYMENT WITH POLYETHYLENE PASSIVE SAMPLING DEVICES

PubMed Central

O’Connell, Steven G.; McCartney, Melissa A.; Paulik, L. Blair; Allan, Sarah E.; Tidwell, Lane G.; Wilson, Glenn; Anderson, Kim A.

2014-01-01

Sequestering semi-polar compounds can be difficult with low-density polyethylene (LDPE), but those pollutants may be more efficiently absorbed using silicone. In this work, optimized methods for cleaning, infusing reference standards, and polymer extraction are reported along with field comparisons of several silicone materials for polycyclic aromatic hydrocarbons (PAHs) and pesticides. In a final field demonstration, the most optimal silicone material is coupled with LDPE in a large-scale study to examine PAHs in addition to oxygenated-PAHs (OPAHs) at a Superfund site. OPAHs exemplify a sensitive range of chemical properties to compare polymers (log Kow 0.2–5.3), and transformation products of commonly studied parent PAHs. On average, while polymer concentrations differed nearly 7-fold, water-calculated values were more similar (about 3.5-fold or less) for both PAHs (17) and OPAHs (7). Individual water concentrations of OPAHs differed dramatically between silicone and LDPE, highlighting the advantages of choosing appropriate polymers and optimized methods for pollutant monitoring. PMID:25009960

Straight Talk: The Challenge Before Modern Day Hinduism

PubMed Central

Singh, Ajai R.

2009-01-01

Hinduism, as an institution, offers very little to the poor and underprivileged within its fold. This is one of the prime reasons for voluntary conversion of Hindus from among its members. B.R. Ambedkar and A.R. Rahman provide poignant examples of how lack of education and health facilities for the underprivileged within its fold, respectively, led to their conversion. This can be countered by a movement to provide large-scale quality health [hospitals/PHCs] and educational [schools/colleges] facilities run by Hindu mission organisations spread over the cities and districts of India. A four point-four phase programmme is presented here to outline how this can be achieved. Those who have the genuine interests of Hinduism at heart will have to set such an agenda before them rather than strident and violent affirmations of its glories. One can understand the reasons for such stridency, but it is time it got converted into constructive affirmative action to keep the flock. PMID:21836787

High-resolution seismic reflection profiling for mapping shallow aquifers in Lee County, Florida

USGS Publications Warehouse

Missimer, T.M.; Gardner, Richard Alfred

1976-01-01

High-resolution continuous seismic reflection profiling equipment was utilized to define the configuration of sedimentary layers underlying part of Lee County, Florida. About 45 miles (72 kilometers) of profile were made on the Caloosahatchee River Estuary and San Carlos Bay. Two different acoustic energy sources, a high resolution boomer and a 45-electrode high resolution sparker, both having a power input of 300 joules, were used to obtain both adequate penetration and good resolution. The seismic profiles show that much of the strata of middle Miocene to Holocene age apparently are extensively folded but not faulted. Initial interpretations indicate that: (1) the top of the Hawthorn Formation (which contains the upper Hawthorn aquifer) has much relief due chiefly to apparent folding; (2) the limestone, sandstone, and unconsolidated sand and phosphorite, which together compose the sandstone aquifer, appear to be discontinuous; (3) the green clay unit of the Tamiami Formation contains large scale angular beds dipping eastward; and (4) numerous deeply cut alluvium-filled paleochannels underlie the Caloosahatchee River. (Woodard-USGS)

Straight talk: the challenge before modern day hinduism.

PubMed

Singh, Ajai R

2009-01-01

Hinduism, as an institution, offers very little to the poor and underprivileged within its fold. This is one of the prime reasons for voluntary conversion of Hindus from among its members. B.R. Ambedkar and A.R. Rahman provide poignant examples of how lack of education and health facilities for the underprivileged within its fold, respectively, led to their conversion. This can be countered by a movement to provide large-scale quality health [hospitals/PHCs] and educational [schools/colleges] facilities run by Hindu mission organisations spread over the cities and districts of India. A four point-four phase programmme is presented here to outline how this can be achieved. Those who have the genuine interests of Hinduism at heart will have to set such an agenda before them rather than strident and violent affirmations of its glories. One can understand the reasons for such stridency, but it is time it got converted into constructive affirmative action to keep the flock.

The three-dimensional architecture of a bacterial genome and its alteration by genetic perturbation.

PubMed

Umbarger, Mark A; Toro, Esteban; Wright, Matthew A; Porreca, Gregory J; Baù, Davide; Hong, Sun-Hae; Fero, Michael J; Zhu, Lihua J; Marti-Renom, Marc A; McAdams, Harley H; Shapiro, Lucy; Dekker, Job; Church, George M

2011-10-21

We have determined the three-dimensional (3D) architecture of the Caulobacter crescentus genome by combining genome-wide chromatin interaction detection, live-cell imaging, and computational modeling. Using chromosome conformation capture carbon copy (5C), we derive ~13 kb resolution 3D models of the Caulobacter genome. The resulting models illustrate that the genome is ellipsoidal with periodically arranged arms. The parS sites, a pair of short contiguous sequence elements known to be involved in chromosome segregation, are positioned at one pole, where they anchor the chromosome to the cell and contribute to the formation of a compact chromatin conformation. Repositioning these elements resulted in rotations of the chromosome that changed the subcellular positions of most genes. Such rotations did not lead to large-scale changes in gene expression, indicating that genome folding does not strongly affect gene regulation. Collectively, our data suggest that genome folding is globally dictated by the parS sites and chromosome segregation. Copyright © 2011 Elsevier Inc. All rights reserved.

High dimensional biological data retrieval optimization with NoSQL technology.

PubMed

Wang, Shicai; Pandis, Ioannis; Wu, Chao; He, Sijin; Johnson, David; Emam, Ibrahim; Guitton, Florian; Guo, Yike

2014-01-01

High-throughput transcriptomic data generated by microarray experiments is the most abundant and frequently stored kind of data currently used in translational medicine studies. Although microarray data is supported in data warehouses such as tranSMART, when querying relational databases for hundreds of different patient gene expression records queries are slow due to poor performance. Non-relational data models, such as the key-value model implemented in NoSQL databases, hold promise to be more performant solutions. Our motivation is to improve the performance of the tranSMART data warehouse with a view to supporting Next Generation Sequencing data. In this paper we introduce a new data model better suited for high-dimensional data storage and querying, optimized for database scalability and performance. We have designed a key-value pair data model to support faster queries over large-scale microarray data and implemented the model using HBase, an implementation of Google's BigTable storage system. An experimental performance comparison was carried out against the traditional relational data model implemented in both MySQL Cluster and MongoDB, using a large publicly available transcriptomic data set taken from NCBI GEO concerning Multiple Myeloma. Our new key-value data model implemented on HBase exhibits an average 5.24-fold increase in high-dimensional biological data query performance compared to the relational model implemented on MySQL Cluster, and an average 6.47-fold increase on query performance on MongoDB. The performance evaluation found that the new key-value data model, in particular its implementation in HBase, outperforms the relational model currently implemented in tranSMART. We propose that NoSQL technology holds great promise for large-scale data management, in particular for high-dimensional biological data such as that demonstrated in the performance evaluation described in this paper. We aim to use this new data model as a basis for migrating tranSMART's implementation to a more scalable solution for Big Data.

High dimensional biological data retrieval optimization with NoSQL technology

PubMed Central

2014-01-01

Background High-throughput transcriptomic data generated by microarray experiments is the most abundant and frequently stored kind of data currently used in translational medicine studies. Although microarray data is supported in data warehouses such as tranSMART, when querying relational databases for hundreds of different patient gene expression records queries are slow due to poor performance. Non-relational data models, such as the key-value model implemented in NoSQL databases, hold promise to be more performant solutions. Our motivation is to improve the performance of the tranSMART data warehouse with a view to supporting Next Generation Sequencing data. Results In this paper we introduce a new data model better suited for high-dimensional data storage and querying, optimized for database scalability and performance. We have designed a key-value pair data model to support faster queries over large-scale microarray data and implemented the model using HBase, an implementation of Google's BigTable storage system. An experimental performance comparison was carried out against the traditional relational data model implemented in both MySQL Cluster and MongoDB, using a large publicly available transcriptomic data set taken from NCBI GEO concerning Multiple Myeloma. Our new key-value data model implemented on HBase exhibits an average 5.24-fold increase in high-dimensional biological data query performance compared to the relational model implemented on MySQL Cluster, and an average 6.47-fold increase on query performance on MongoDB. Conclusions The performance evaluation found that the new key-value data model, in particular its implementation in HBase, outperforms the relational model currently implemented in tranSMART. We propose that NoSQL technology holds great promise for large-scale data management, in particular for high-dimensional biological data such as that demonstrated in the performance evaluation described in this paper. We aim to use this new data model as a basis for migrating tranSMART's implementation to a more scalable solution for Big Data. PMID:25435347

Structure contour map of the greater Green River basin, Wyoming, Colorado, and Utah

USGS Publications Warehouse

Lickus, M.R.; Law, B.E.

1988-01-01

The Greater Green River basin of Wyoming, Colorado, and Utah contains five basins and associated major uplifts (fig. 1). Published structure maps of the region have commonly used the top of the Lower Cretaceous Dakota Sandstone as a structural datum (Petroleum Ownership Map Company (POMCO), 1984; Rocky Mountain Association of Geologists, 1972). However, because relatively few wells in this area penetrate the Dakota, the Dakota structural datum has to be constructed by projecting down from shallower wells. Extrapolating in this manner may produce errors in the map. The primary purpose of this report is to present a more reliable structure contour map of the Greater Green River basin based on datums that are penetrated by many wells. The final map shows the large- to small-scale structures present in the Greater Green River basin. The availability of subsurface control and the map scale determined whether or not a structural feature was included on the map. In general, large structures such as the Moxa arch, Pinedale anticline, and other large folds were placed on the map based solely on the structure contours. In comparison, smaller folds and some faults were placed on the map based on structure contours and other reports (Bader 1987; Bradley 1961; Love and Christiansen, 1985; McDonald, 1975; Roehler, 1979; Wyoming Geological Association Oil and Gas Symposium Committee, 1979). State geologic maps and other reports were used to position basin margin faults (Bryant, 1985; Gries, 1983a, b; Hansen 1986; Hintze, 1980; Love and Christiansen, 1985; Tweto, 1979, 1983). In addition, an interpreted east-west-trending regional seismic line by Garing and Tainter (1985), which shows the basin configuration in cross-section, was helpful in locating buried faults, such as the high-angle reverse or thrust fault along the west flank of the Rock Springs uplift.

Fluvial-Deltaic Strata as a High-Resolution Recorder of Fold Growth and Fault Slip

NASA Astrophysics Data System (ADS)

Anastasio, D. J.; Kodama, K. P.; Pazzaglia, F. P.

2008-12-01

Fluvial-deltaic systems characterize the depositional record of most wedge-top and foreland basins, where the synorogenic stratigraphy responds to interactions between sediment supply driven by tectonic uplift, climate modulated sea level change and erosion rate variability, and fold growth patterns driven by unsteady fault slip. We integrate kinematic models of fault-related folds with growth strata and fluvial terrace records to determine incremental rates of shortening, rock uplift, limb tilting, and fault slip with 104-105 year temporal resolution in the Pyrenees and Apennines. At Pico del Aguila anticline, a transverse dècollement fold along the south Pyrenean mountain front, formation-scale synorogenic deposition and clastic facies patterns in prodeltaic and slope facies reflect tectonic forcing of sediment supply, sea level variability controlling delta front position, and climate modulated changes in terrestrial runoff. Growth geometries record a pinned anticline and migrating syncline hinges during folding above the emerging Guarga thrust sheet. Lithologic and anhysteretic remanent magnetization (ARM) data series from the Eocene Arguis Fm. show cyclicity at Milankovitch frequencies allowing detailed reconstruction of unsteady fold growth. Multiple variations in limb tilting rates from <8° to 28°/my over 7my are attributed to unsteady fault slip along the roof ramp and basal dècollement. Along the northern Apennine mountain front, the age and geometry of strath terraces preserved across the Salsomaggiore anticline records the Pleistocene-Recent kinematics of the underlying fault-propagation fold as occurring with a fixed anticline hinge, a rolling syncline hinge, and along-strike variations in uplift and forelimb tilting. The uplifted intersection of terrace deposits documents syncline axial surface migration and underlying fault-tip propagation at a rate of ~1.4 cm/yr since the Middle Pleistocene. Because this record of fault slip coincides with the well-known large amplitude oscillations in global climate that contribute to the filling and deformation of the Po foreland, we hypothesize that climatically-modulated surface processes are reflected in the observed rates of fault slip and fold growth.

Structural geology of the Rub' Al-Khali Basin, Saudi Arabia

NASA Astrophysics Data System (ADS)

Stewart, S. A.

2016-10-01

The Rub' Al-Khali basin lies below a Quaternary sand sea, and the structural evolution from the Late Precambrian to Neogene is known only from reflection seismic, gravity, and magnetic data, and wells. Gravity and magnetic data show north-south and northwest-southeast trends, matching mapped Precambrian faults. The deepest structures imaged on reflection seismic data are undrilled Precambrian rifts filled with layered strata at depths up to 13 km. The distribution of Ediacaran-Cambrian Ara/Hormuz mobile salt is restricted to an embayment in the eastern Rub' Al-Khali. The Precambrian rifts show local inversion and were peneplained at base Phanerozoic. A broad crustal-scale fold (Qatar Arch) developed in the Carboniferous and amplified in the Late Triassic, separating subbasins in the west and east Rub' Al-Khali. A phase of kilometer-scale folding occurred in the Late Cretaceous, coeval with thrusting and ophiolite obduction in eastern Oman. These folds trend predominantly north-south, oblique to the northwesterly shortening direction, and occasionally have steep fault zones close to their axial surfaces. The trend and location of these folds closely matches the Precambrian lineaments identified in this study, demonstrating preferential reactivation of basement structures. Compression along the Zagros suture reactivated these folds in the Neogene, this time the result of highly oblique, north-northeast to south-southwest shortening. Cretaceous-Tertiary fold style is interpreted as transpression with minor strain partitioning. Permian, Jurassic, and Eocene evaporite horizons played no role in the structural evolution of the basin, but the Eocene evaporites caused widespread kilometer-scale dissolution collapse structures in the basin center.

Complex deformation associated with anhydrite layers in the Tromsø Basin, SW Barents Sea.

NASA Astrophysics Data System (ADS)

Marfo, George; Olakunle Omosanya, Kamaldeen; Johansen, Ståle Emil; Zervas, Ioannis

2017-04-01

Internal and external deformation associated with salt structures is of prime interest due to their economic importance as hydrocarbon seals, reservoirs, repositories for chemical waste and their implication on drilling. Salt structures are often associated with anhydrites, which may 'cap' or are enclosed within the allochthonous salt structures. Despite their economic importance, the internal and external structures of evaporites remain poorly studied from field and seismic data due to the sparse outcrops of evaporites and poor seismic imaging. The zero-phased, normal polarity, high resolution multiple 2D seismic data, in combination with detailed interpretation of wireline logs provide an excellent study into the salt structures, and offers a good opportunity to investigate the dynamics, geometries and mechanisms driving deformation of internal and external salt layers associated with the Late Carboniferous to Early Permian Salt structures in the Tromsø Basin. The methods include seismic interpretation and the application of multiple seismic attributes to map stratigraphic units and discontinuities. Our results show that the anhydrite layers are marked by high amplitude reflections at the crests and flanks or fully enclosed within the salt diapirs. Crestal and lateral anhydrite caprocks represent external salt structures whilst the entrained anhydrites or stringers are intrasalt structures. Anhydrite caprocks generally show structural styles such as faults and large-scale folds which are harmonic to the top salt structure. In contrast, anhydrite stringers show folds of varying scale, which are harmonic to disharmonic to the top salt structure. Boudins and steeply dipping stringer fragments are also interpreted within the stringers. Caprock deformation is attributed to salt upwelling. Folding and boudinaging of originally horizontal and continuous stringer layers formed from a multiphase superimposed sequence of ductile and brittle deformation in response to complex multi-dimensional salt flow. Internal salt flow involves radial and tangential compression, which leads to dominant fold structures near the margins. Boudins on the lower flanks of the diapir formed due radial extension. Our study further demonstrates that differential geometries exhibited by the different anhydrite groups imply that the mechanisms deforming internal and external salt structures are different. The results from this study are comparable to observations from salt mines, field exposures, scaled physical and numerical models.

Self-folding origami at any energy scale

NASA Astrophysics Data System (ADS)

Pinson, Matthew B.; Stern, Menachem; Carruthers Ferrero, Alexandra; Witten, Thomas A.; Chen, Elizabeth; Murugan, Arvind

2017-05-01

Programmable stiff sheets with a single low-energy folding motion have been sought in fields ranging from the ancient art of origami to modern meta-materials research. Despite such attention, only two extreme classes of crease patterns are usually studied; special Miura-Ori-based zero-energy patterns, in which crease folding requires no sheet bending, and random patterns with high-energy folding, in which the sheet bends as much as creases fold. We present a physical approach that allows systematic exploration of the entire space of crease patterns as a function of the folding energy. Consequently, we uncover statistical results in origami, finding the entropy of crease patterns of given folding energy. Notably, we identify three classes of Mountain-Valley choices that have widely varying `typical' folding energies. Our work opens up a wealth of experimentally relevant self-folding origami designs not reliant on Miura-Ori, the Kawasaki condition or any special symmetry in space.

Overlooked Short Toxin-Like Proteins: A Shortcut to Drug Design

PubMed Central

Linial, Michal

2017-01-01

Short stable peptides have huge potential for novel therapies and biosimilars. Cysteine-rich short proteins are characterized by multiple disulfide bridges in a compact structure. Many of these metazoan proteins are processed, folded, and secreted as soluble stable folds. These properties are shared by both marine and terrestrial animal toxins. These stable short proteins are promising sources for new drug development. We developed ClanTox (classifier of animal toxins) to identify toxin-like proteins (TOLIPs) using machine learning models trained on a large-scale proteomic database. Insects proteomes provide a rich source for protein innovations. Therefore, we seek overlooked toxin-like proteins from insects (coined iTOLIPs). Out of 4180 short (<75 amino acids) secreted proteins, 379 were predicted as iTOLIPs with high confidence, with as many as 30% of the genes marked as uncharacterized. Based on bioinformatics, structure modeling, and data-mining methods, we found that the most significant group of predicted iTOLIPs carry antimicrobial activity. Among the top predicted sequences were 120 termicin genes from termites with antifungal properties. Structural variations of insect antimicrobial peptides illustrate the similarity to a short version of the defensin fold with antifungal specificity. We also identified 9 proteins that strongly resemble ion channel inhibitors from scorpion and conus toxins. Furthermore, we assigned functional fold to numerous uncharacterized iTOLIPs. We conclude that a systematic approach for finding iTOLIPs provides a rich source of peptides for drug design and innovative therapeutic discoveries. PMID:29109389

Prairie strips improve biodiversity and the delivery of multiple ecosystem services from corn–soybean croplands

PubMed Central

Helmers, Matthew J.; Liebman, Matt; James, David E.; Kolka, Randall K.; O’Neal, Matthew E.; Tomer, Mark D.; Tyndall, John C.; Asbjornsen, Heidi; Drobney, Pauline; Neal, Jeri; Van Ryswyk, Gary; Witte, Chris

2017-01-01

Loss of biodiversity and degradation of ecosystem services from agricultural lands remain important challenges in the United States despite decades of spending on natural resource management. To date, conservation investment has emphasized engineering practices or vegetative strategies centered on monocultural plantings of nonnative plants, largely excluding native species from cropland. In a catchment-scale experiment, we quantified the multiple effects of integrating strips of native prairie species amid corn and soybean crops, with prairie strips arranged to arrest run-off on slopes. Replacing 10% of cropland with prairie strips increased biodiversity and ecosystem services with minimal impacts on crop production. Compared with catchments containing only crops, integrating prairie strips into cropland led to greater catchment-level insect taxa richness (2.6-fold), pollinator abundance (3.5-fold), native bird species richness (2.1-fold), and abundance of bird species of greatest conservation need (2.1-fold). Use of prairie strips also reduced total water runoff from catchments by 37%, resulting in retention of 20 times more soil and 4.3 times more phosphorus. Corn and soybean yields for catchments with prairie strips decreased only by the amount of the area taken out of crop production. Social survey results indicated demand among both farming and nonfarming populations for the environmental outcomes produced by prairie strips. If federal and state policies were aligned to promote prairie strips, the practice would be applicable to 3.9 million ha of cropland in Iowa alone. PMID:28973922

Captopril and the intestinal response to hemorrhagic shock.

PubMed

Rosenfeld, L M; Cooper, H S

1982-09-01

In order to help clarify the role of the renin-angiotensin system in the evolution of the post-hemorrhagic circulatory shock syndrome, captopril, a potent inhibitor of the conversion of angiotensin I to angiotensin II, was infused into a hemorrhagic shock model in the cat. The hemorrhage protocol had arterial blood withdrawn until a mean arterial blood pressure (MABP) of 40 mm Hg developed. Oligemia was maintained for a period of 2.5 hr, after which time, all remaining shed blood was reinfused and the cats observed for an additional 2 hr. Coincident with the large reduction in MABP, superior mesenteric artery flow (SMAF) was similarly reduced as recorded by a noncannulating electromagnetic flow probe fitted around the artery. Post-oligemic plasma activities of cathepsin D (CD) and alkaline phosphatase (AP) were elevated 11-fold and 3-fold respectively; intestinal morphological damage was graded at 2.8 +/- 0.6 on a 0-4 scale of increasing severity (control: 0.03 +/- 0.02). Captopril was administered at an initial priming dose of 0.5 mg/kg followed by a continuous infusion of 0.5 mg/kg/hr. Improved post-reinfusion maintenance of MABP and SMAF was noted. Plasma elevations in enzyme activity were more moderate: 8-fold for CD, 1.5-fold for AP. Intestinal morphologic damage was graded at 2.5 +/- 0.3. Blockade of angiotensin II formation by captopril thus demonstrated beneficial effects on post-oligemic hemodynamic status and on the degree of cellular enzyme release without significant improvement in intestinal morphology.

Insights on fluid-rock interaction evolution during deformation from fracture network geochemistry at reservoir-scale

NASA Astrophysics Data System (ADS)

Beaudoin, Nicolas; Koehn, Daniel; Lacombe, Olivier; Bellahsen, Nicolas; Emmanuel, Laurent

2015-04-01

Fluid migration and fluid-rock interactions during deformation is a challenging problematic to picture. Numerous interplays, as between porosity-permeability creation and clogging, or evolution of the mechanical properties of rock, are key features when it comes to monitor reservoir evolution, or to better understand seismic cycle n the shallow crust. These phenomenoms are especially important in foreland basins, where various fluids can invade strata and efficiently react with limestones, altering their physical properties. Stable isotopes (O, C, Sr) measurements and fluid inclusion microthermometry of faults cement and veins cement lead to efficient reconstruction of the origin, temperature and migration pathways for fluids (i.e. fluid system) that precipitated during joints opening or faults activation. Such a toolbox can be used on a diffuse fracture network that testifies the local and/or regional deformation history experienced by the rock at reservoir-scale. This contribution underlines the advantages and limits of geochemical studies of diffuse fracture network at reservoir-scale by presenting results of fluid system reconstruction during deformation in folded structures from various thrust-belts, tectonic context and deformation history. We compare reconstructions of fluid-rock interaction evolution during post-deposition, post-burial growth of basement-involved folds in the Sevier-Laramide American Rocky Mountains foreland, a reconstruction of fluid-rock interaction evolution during syn-depostion shallow detachment folding in the Southern Pyrenean foreland, and a preliminary reconstruction of fluid-rock interactions in a post-deposition, post-burial development of a detachment fold in the Appenines. Beyond regional specification for the nature of fluids, a common behavior appears during deformation as in every fold, curvature-related joints (related either to folding or to foreland flexure) connected vertically the pre-existing stratified fluid system. The lengthscale of the migration and the nature of invading fluids during these connections is different in every studied example, and can be related to the tectonic nature of the fold, along with the burial depth at the time of deformation. Thus, to decipher fluid-fracture relationships provides insights to better reconstruct the mechanisms of deformation at reservoir-scale.

Magnetorotational dynamo action in the shearing box

NASA Astrophysics Data System (ADS)

Walker, Justin; Boldyrev, Stanislav

2017-09-01

Magnetic dynamo action caused by the magnetorotational instability is studied in the shearing-box approximation with no imposed net magnetic flux. Consistent with recent studies, the dynamo action is found to be sensitive to the aspect ratio of the box: it is much easier to obtain in tall boxes (stretched in the direction normal to the disc plane) than in long boxes (stretched in the radial direction). Our direct numerical simulations indicate that the dynamo is possible in both cases, given a large enough magnetic Reynolds number. To explain the relatively larger effort required to obtain the dynamo action in a long box, we propose that the turbulent eddies caused by the instability most efficiently fold and mix the magnetic field lines in the radial direction. As a result, in the long box the scale of the generated strong azimuthal (stream-wise directed) magnetic field is always comparable to the scale of the turbulent eddies. In contrast, in the tall box the azimuthal magnetic flux spreads in the vertical direction over a distance exceeding the scale of the turbulent eddies. As a result, different vertical sections of the tall box are permeated by large-scale non-zero azimuthal magnetic fluxes, facilitating the instability. In agreement with this picture, the cases when the dynamo is efficient are characterized by a strong intermittency of the local azimuthal magnetic fluxes.

Satellite measurements reveal strong anisotropy in spatial coherence of climate variations over the Tibet Plateau.

PubMed

Chen, Deliang; Tian, Yudong; Yao, Tandong; Ou, Tinghai

2016-08-24

This study uses high-resolution, long-term satellite observations to evaluate the spatial scales of the climate variations across the Tibet Plateau (TP). Both land surface temperature and precipitation observations of more than 10 years were analysed with a special attention to eight existing ice-core sites in the TP. The temporal correlation for the monthly or annual anomalies between any two points decreases exponentially with their spatial distance, and we used the e-folding decay constant to quantify the spatial scales. We found that the spatial scales are strongly direction-dependent, with distinctive patterns in the west-east and south-north orientations, for example. Meanwhile, in the same directions the scales are largely symmetric backward and forward. Focusing on the west-east and south-north directions, we found the spatial coherence in the first is generally stronger than in the second. The annual surface temperature had typical spatial scales of 302-480 km, while the annual precipitation showed smaller scales of 111-182 km. The majority of the eight ice-core sites exhibit scales much smaller than the typical scales over the TP as a whole. These results provide important observational basis for the selection of appropriate downscaling strategies, deployment of climate-data collection networks, and interpreting paleoclimate reconstructions.

Satellite measurements reveal strong anisotropy in spatial coherence of climate variations over the Tibet Plateau

NASA Astrophysics Data System (ADS)

Chen, Deliang; Tian, Yudong; Yao, Tandong; Ou, Tinghai

2016-08-01

This study uses high-resolution, long-term satellite observations to evaluate the spatial scales of the climate variations across the Tibet Plateau (TP). Both land surface temperature and precipitation observations of more than 10 years were analysed with a special attention to eight existing ice-core sites in the TP. The temporal correlation for the monthly or annual anomalies between any two points decreases exponentially with their spatial distance, and we used the e-folding decay constant to quantify the spatial scales. We found that the spatial scales are strongly direction-dependent, with distinctive patterns in the west-east and south-north orientations, for example. Meanwhile, in the same directions the scales are largely symmetric backward and forward. Focusing on the west-east and south-north directions, we found the spatial coherence in the first is generally stronger than in the second. The annual surface temperature had typical spatial scales of 302-480 km, while the annual precipitation showed smaller scales of 111-182 km. The majority of the eight ice-core sites exhibit scales much smaller than the typical scales over the TP as a whole. These results provide important observational basis for the selection of appropriate downscaling strategies, deployment of climate-data collection networks, and interpreting paleoclimate reconstructions.

Satellite measurements reveal strong anisotropy in spatial coherence of climate variations over the Tibet Plateau

PubMed Central

Chen, Deliang; Tian, Yudong; Yao, Tandong; Ou, Tinghai

2016-01-01

This study uses high-resolution, long-term satellite observations to evaluate the spatial scales of the climate variations across the Tibet Plateau (TP). Both land surface temperature and precipitation observations of more than 10 years were analysed with a special attention to eight existing ice-core sites in the TP. The temporal correlation for the monthly or annual anomalies between any two points decreases exponentially with their spatial distance, and we used the e-folding decay constant to quantify the spatial scales. We found that the spatial scales are strongly direction-dependent, with distinctive patterns in the west-east and south-north orientations, for example. Meanwhile, in the same directions the scales are largely symmetric backward and forward. Focusing on the west-east and south-north directions, we found the spatial coherence in the first is generally stronger than in the second. The annual surface temperature had typical spatial scales of 302–480 km, while the annual precipitation showed smaller scales of 111–182 km. The majority of the eight ice-core sites exhibit scales much smaller than the typical scales over the TP as a whole. These results provide important observational basis for the selection of appropriate downscaling strategies, deployment of climate-data collection networks, and interpreting paleoclimate reconstructions. PMID:27553388

Stress and strain patterns, kinematics and deformation mechanisms in a basement-cored anticline: Sheep Mountain Anticline, Wyoming

NASA Astrophysics Data System (ADS)

Amrouch, Khalid; Lacombe, Olivier; Bellahsen, Nicolas; Daniel, Jean-Marc; Callot, Jean-Paul

2010-02-01

In order to characterize and compare the stress-strain record prior to, during, and just after folding at the macroscopic and the microscopic scales and to provide insights into stress levels sustained by folded rocks, we investigate the relationship between the stress-strain distribution in folded strata derived from fractures, striated microfaults, and calcite twins and the development of the Laramide, basement-cored Sheep Mountain Anticline, Wyoming. Tectonic data were mainly collected in Lower Carboniferous to Permian carbonates and sandstones. In both rock matrix and veins, calcite twins recorded three different tectonic stages: the first stage is a pre-Laramide (Sevier) layer-parallel shortening (LPS) parallel to fold axis, the second one is a Laramide LPS perpendicular to the fold axis, and the third stage corresponds to Laramide late fold tightening with compression also perpendicular to the fold axis. Stress and strain orientations and regimes at the microscale agree with the polyphase stress evolution revealed by populations of fractures and striated microfaults, testifying for the homogeneity of stress record at different scales through time. Calcite twin analysis additionally reveals significant variations of differential stress magnitudes between fold limbs. Our results especially point to an increase of differential stress magnitudes related to Laramide LPS from the backlimb to the forelimb of the fold possibly in relation with motion of an underlying basement thrust fault that likely induced stress concentrations at its upper tip. This result is confirmed by a simple numerical model. Beyond regional implications, this study highlights the potential of calcite twin analyses to yield a representative quantitative picture of stress and strain patterns related to folding.

Nanoscale viscoelasticity of extracellular matrix proteins in soft tissues: A multiscale approach.

PubMed

Miri, Amir K; Heris, Hossein K; Mongeau, Luc; Javid, Farhad

2014-02-01

It is hypothesized that the bulk viscoelasticity of soft tissues is determined by two length-scale-dependent mechanisms: the time-dependent response of the extracellular matrix (ECM) proteins at the nanometer scale and the biophysical interactions between the ECM solid structure and interstitial fluid at the micrometer scale. The latter is governed by poroelasticity theory assuming free motion of the interstitial fluid within the porous ECM structure. In a recent study (Heris, H.K., Miri, A.K., Tripathy, U., Barthelat, F., Mongeau, L., 2013. J. Mech. Behav. Biomed. Mater.), atomic force microscopy was used to measure the response of porcine vocal folds to a creep loading and a 50-nm sinusoidal oscillation. A constitutive model was calibrated and verified using a finite element model to accurately predict the nanoscale viscoelastic moduli of ECM. A generally good correlation was obtained between the predicted variation of the viscoelastic moduli with depth and that of hyaluronic acids in vocal fold tissue. We conclude that hyaluronic acids may regulate vocal fold viscoelasticity. The proposed methodology offers a characterization tool for biomaterials used in vocal fold augmentations. © 2013 Elsevier Ltd. All rights reserved.

Quartz c-axis fabrics in constrictionally strained orthogneisses: implications for the evolution of the Orlica-Śnieżnik Dome, the Sudetes, Poland

NASA Astrophysics Data System (ADS)

Żelaźniewicz, Andrzej; Kromuszczyńska, Olga; Biegała, Natalia

2013-12-01

Żelaźniewicz, A., Kromuszczyńska, O. and Biegała, N. 2013. Quartz c-axis fabrics in constrictionally strained orthogneisses: implications for the evolution of the Orlica-Śnieżnik Dome, the Sudetes, Poland. Acta Geologica Polonica, 63(4), 697-722, Warszawa. The Orlica-Śnieżnik Dome (OSD), NE Bohemian Massif, contains in its core several gneiss variants with protoliths dated at ~500 Ma. In the western limb of the OSD, rodding augen gneisses (Spalona gneiss unit) are mainly L>S tectonites with a prominent stretching lineation. The few quartz LPO studies have produced somewhat discrepant results. Reexamination of these rocks revealed that texture formation was a protracted, multistage process that involved strain partitioning with changing strain rate and kinematics in a general shear regime at temperatures of the amphibolite facies (450-600°C). Quartz c-axis microfabrics show complex yet reproducible patterns that developed under the joint control of strain geometry and temperature; thus the LPOs are mixed features represented by pseudogirdle patterns. Domainal differences in quartz microfabrics (ribbons, tails, quartzo-feldspathic aggregate) are common in the Spalona orthogneisses but uncommon in the sheared migmatitic gneisses. In the latter rocks, the constrictional strain was imposed on the originally planar fabric defined by high-temperature migmatitic layering. The constrictional fabric of the Spalona gneisses may have developed in the hinge zones of kilometer-scale folds, where the elongation occurred parallel to the fold axes. Other occurrences of rodding gneisses throughout the Orlica-Śnieżnik Dome are thought to occupy similar structural positions, which would point to the significance of large-scale folds in the tectonic structure of the dome.

Petrotectonic framework of granulites from northern part of Chilka Lake area, Eastern Ghats Belt, India: Compressional vis-à-vis transpressional tectonics

NASA Astrophysics Data System (ADS)

Das, Kaushik; Bose, Sankar; Karmakar, Subrata; Chakraborty, Supriya

2012-02-01

Granulite-facies rocks occurring north-east of the Chilka Lake anothosite (Balugan Massif) show a complex metamorphic and deformation history. The M1-D1 stage is identified only through microscopic study by the presence of S1 internal foliation shown by the M1 assemblage sillimanite-quartz-plagioclase-biotite within garnet porphyroblasts of the aluminous granulites and this fabric is obliterated in outcrop to map-scale by subsequent deformations. S2 fabric was developed at peak metamorphic condition (M2-D2) and is shown by gneissic banding present in all lithological units. S3 fabric was developed due to D3 deformation and it is tectonically transposed parallel to S2 regionally except at the hinge zone of the F3 folds. The transposed S2/S3 fabric is the regional characteristic structure of the area. The D4 event produced open upright F4 folds, but was weak enough to develop any penetrative foliation in the rocks except few spaced cleavages that developed in the quartzite/garnet-sillimanite gneiss. Petrological data suggest that the M4-D4 stage actually witnessed reactivation of the lower crust by late distinct tectonothermal event. Presence of transposed S2/S3 fabric within the anorthosite arguably suggests that the pluton was emplaced before or during the M3-D3 event. Field-based large-scale structural analyses and microfabric analyses of the granulites reveal that this terrain has been evolved through superposed folding events with two broadly perpendicular compression directions without any conclusive evidence for transpressional tectonics as argued by earlier workers. Tectonothermal history of these granulites spanning in Neoproterozoic time period is dominated by compressional tectonics with associated metamorphism at deep crust.

The Farther the Better: Effects of Multiple Environmental Variables on Reef Fish Assemblages along a Distance Gradient from River Influences.

PubMed

Neves, Leonardo M; Teixeira-Neves, Tatiana P; Pereira-Filho, Guilherme H; Araújo, Francisco G

2016-01-01

The conservation and management of site-attached assemblages of coastal reefs are particularly challenging because of the tremendous environmental variation that exists at small spatial scales. In this sense, understanding the primary sources of variation in spatial patterns of the biota is fundamental for designing effective conservation policies. We investigated spatial variation in fish assemblages around the windward and leeward sides of coastal islands situated across a gradient of riverine influence (13 km in length). Specifically, relationships between rocky reef fish assemblages and benthic, topographic and physical predictors were assessed. We hypothesized that river induced disturbances may overcome local habitat features in modeling spatial patterns of fish distribution. Fish assemblages varied primarily due to the strong directional gradient of riverine influence (22.6% of the estimated components of variation), followed by topographic complexity (15%), wave exposure (9.9%), and benthic cover (8%). The trophic structure of fish assemblages changed from having a high abundance of invertebrate feeders in macroalgae-dominated reefs close to river mouths to a high proportion of herbivores, planktivores and invertebrate feeder species in reefs with large boulders covered by epilithic algal matrices, as the distance from rivers increased. This gradient led to an increase of 4.5-fold in fish richness and fish trophic group diversity, 11-fold in fish biomass and 10-fold in fish abundance. Our results have implications for the conservation and monitoring of assemblages patchily distributed at small spatial scales. The major role of distance from river influences on fish assemblages rather than benthic cover and topographic complexity suggest that managing land-based activities should be a conservation priority toward reef restoration.

The Farther the Better: Effects of Multiple Environmental Variables on Reef Fish Assemblages along a Distance Gradient from River Influences

PubMed Central

Neves, Leonardo M.; Teixeira-Neves, Tatiana P.; Pereira-Filho, Guilherme H.; Araújo, Francisco G.

2016-01-01

The conservation and management of site-attached assemblages of coastal reefs are particularly challenging because of the tremendous environmental variation that exists at small spatial scales. In this sense, understanding the primary sources of variation in spatial patterns of the biota is fundamental for designing effective conservation policies. We investigated spatial variation in fish assemblages around the windward and leeward sides of coastal islands situated across a gradient of riverine influence (13 km in length). Specifically, relationships between rocky reef fish assemblages and benthic, topographic and physical predictors were assessed. We hypothesized that river induced disturbances may overcome local habitat features in modeling spatial patterns of fish distribution. Fish assemblages varied primarily due to the strong directional gradient of riverine influence (22.6% of the estimated components of variation), followed by topographic complexity (15%), wave exposure (9.9%), and benthic cover (8%). The trophic structure of fish assemblages changed from having a high abundance of invertebrate feeders in macroalgae-dominated reefs close to river mouths to a high proportion of herbivores, planktivores and invertebrate feeder species in reefs with large boulders covered by epilithic algal matrices, as the distance from rivers increased. This gradient led to an increase of 4.5-fold in fish richness and fish trophic group diversity, 11-fold in fish biomass and 10-fold in fish abundance. Our results have implications for the conservation and monitoring of assemblages patchily distributed at small spatial scales. The major role of distance from river influences on fish assemblages rather than benthic cover and topographic complexity suggest that managing land-based activities should be a conservation priority toward reef restoration. PMID:27907017

Self-folding mechanics of graphene tearing and peeling from a substrate

NASA Astrophysics Data System (ADS)

He, Ze-Zhou; Zhu, Yin-Bo; Wu, Heng-An

2018-06-01

Understanding the underlying mechanism in the tearing and peeling processes of graphene is crucial for the further hierarchical design of origami-like folding and kirigami-like cutting of graphene. However, the complex effects among bending moduli, adhesion, interlayer interaction, and local crystal structure during origami-like folding and kirigami-like cutting remain unclear, resulting in challenges to the practical applications of existing theoretical and experimental findings as well as to potential manipulations of graphene in metamaterials and nanodevices. Toward this end, classical molecular dynamics (MD) simulations are performed with synergetic theoretical analysis to explore the tearing and peeling of self-folded graphene from a substrate driven by external force and by thermal activation. It is found that the elastic energy localized at the small folding ridge plays a significant role in the crack trajectory. Due to the extremely small bending modulus of monolayer graphene, its taper angle when pulled by an external force follows a scaling law distinct from that in case of bilayer graphene. With the increase in the initial width of the folding ridge, the self-folded graphene, motivated by thermal fluctuations, can be self-assembled by spontaneous self-tearing and peeling from a substrate. Simultaneously, the scaling law between the taper angle and adhesive energy is independent of the motivations for thermal activation-induced self-assembly and external force tearing, providing effective insights into the underlying physics for graphene-based origami-like folding and kirigami-like cutting.

Deformation and kinematics of the central Kirthar Fold Belt, Pakistan

NASA Astrophysics Data System (ADS)

Hinsch, Ralph; Hagedorn, Peter; Asmar, Chloé; Nasim, Muhammad; Aamir Rasheed, Muhammad; Kiely, James M.

2017-04-01

The Kirthar Fold Belt is part of the lateral mountain belts in Pakistan linking the Himalaya orogeny with the Makran accretionary wedge. This region is deforming very oblique/nearly parallel to the regional plate motion vector. The study area is situated between the prominent Chaman strike-slip fault in the West and the un-deformed foreland (Kirthar Foredeep/Middle Indus Basin) in the East. The Kirthar Fold Belt is subdivided into several crustal blocks/units based on structural orientation and deformation style (e.g. Kallat, Khuzdar, frontal Kirthar). This study uses newly acquired and depth-migrated 2D seismic lines, surface geology observations and Google Earth assessments to construct three balanced cross sections for the frontal part of the fold belt. Further work was done in order to insure the coherency of the built cross-sections by taking a closer look at the regional context inferred from published data, simple analogue modelling, and constructed regional sketch sections. The Khuzdar area and the frontal Kirthar Fold Belt are dominated by folding. Large thrusts with major stratigraphic repetitions are not observed. Furthermore, strike-slip faults in the Khuzdar area are scarce and not observed in the frontal Kirthar Fold Belt. The regional structural elevation rises from the foreland across the Kirthar Fold Belt towards the hinterland (Khuzdar area). These observations indicate that basement-involved deformation is present at depth. The domination of folding indicates a weak decollement below the folds (soft-linked deformation). The fold pattern in the Khuzdar area is complex, whereas the large folds of the central Kirthar Fold Belt trend SSW-NNE to N-S and are best described as large detachment folds that have been slightly uplifted by basement involved transpressive deformation underneath. Towards the foreland, the deformation is apparently more hard-linked and involves fault-propagation folding and a small triangle zone in Cretaceous sediments. Shortening is in the order of 21-24% for the frontal structures. The deformation above the weak Eocene Ghazij shales is partly decoupled from the layers underneath, especially where the Ghazij shales are thick. Thus, not all structures visible at surface level in the Kirthar Fold Belt are also present in the deeper section, and vice versa (disharmonic folding). The structural architecture in the frontal central Kirthar Fold Belt shows only convergent structures nearly parallel to the regional plate motion vector of the Indian plate and thus represents an example of extreme strain partitioning.

Communication interval selection in distributed heterogeneous simulation of large-scale dynamical systems

NASA Astrophysics Data System (ADS)

Lucas, Charles E.; Walters, Eric A.; Jatskevich, Juri; Wasynczuk, Oleg; Lamm, Peter T.

2003-09-01

In this paper, a new technique useful for the numerical simulation of large-scale systems is presented. This approach enables the overall system simulation to be formed by the dynamic interconnection of the various interdependent simulations, each representing a specific component or subsystem such as control, electrical, mechanical, hydraulic, or thermal. Each simulation may be developed separately using possibly different commercial-off-the-shelf simulation programs thereby allowing the most suitable language or tool to be used based on the design/analysis needs. These subsystems communicate the required interface variables at specific time intervals. A discussion concerning the selection of appropriate communication intervals is presented herein. For the purpose of demonstration, this technique is applied to a detailed simulation of a representative aircraft power system, such as that found on the Joint Strike Fighter (JSF). This system is comprised of ten component models each developed using MATLAB/Simulink, EASY5, or ACSL. When the ten component simulations were distributed across just four personal computers (PCs), a greater than 15-fold improvement in simulation speed (compared to the single-computer implementation) was achieved.

GeNN: a code generation framework for accelerated brain simulations

NASA Astrophysics Data System (ADS)

Yavuz, Esin; Turner, James; Nowotny, Thomas

2016-01-01

Large-scale numerical simulations of detailed brain circuit models are important for identifying hypotheses on brain functions and testing their consistency and plausibility. An ongoing challenge for simulating realistic models is, however, computational speed. In this paper, we present the GeNN (GPU-enhanced Neuronal Networks) framework, which aims to facilitate the use of graphics accelerators for computational models of large-scale neuronal networks to address this challenge. GeNN is an open source library that generates code to accelerate the execution of network simulations on NVIDIA GPUs, through a flexible and extensible interface, which does not require in-depth technical knowledge from the users. We present performance benchmarks showing that 200-fold speedup compared to a single core of a CPU can be achieved for a network of one million conductance based Hodgkin-Huxley neurons but that for other models the speedup can differ. GeNN is available for Linux, Mac OS X and Windows platforms. The source code, user manual, tutorials, Wiki, in-depth example projects and all other related information can be found on the project website http://genn-team.github.io/genn/.

GeNN: a code generation framework for accelerated brain simulations.

PubMed

Yavuz, Esin; Turner, James; Nowotny, Thomas

2016-01-07

Large-scale numerical simulations of detailed brain circuit models are important for identifying hypotheses on brain functions and testing their consistency and plausibility. An ongoing challenge for simulating realistic models is, however, computational speed. In this paper, we present the GeNN (GPU-enhanced Neuronal Networks) framework, which aims to facilitate the use of graphics accelerators for computational models of large-scale neuronal networks to address this challenge. GeNN is an open source library that generates code to accelerate the execution of network simulations on NVIDIA GPUs, through a flexible and extensible interface, which does not require in-depth technical knowledge from the users. We present performance benchmarks showing that 200-fold speedup compared to a single core of a CPU can be achieved for a network of one million conductance based Hodgkin-Huxley neurons but that for other models the speedup can differ. GeNN is available for Linux, Mac OS X and Windows platforms. The source code, user manual, tutorials, Wiki, in-depth example projects and all other related information can be found on the project website http://genn-team.github.io/genn/.

GeNN: a code generation framework for accelerated brain simulations

PubMed Central

Yavuz, Esin; Turner, James; Nowotny, Thomas

2016-01-01

Large-scale numerical simulations of detailed brain circuit models are important for identifying hypotheses on brain functions and testing their consistency and plausibility. An ongoing challenge for simulating realistic models is, however, computational speed. In this paper, we present the GeNN (GPU-enhanced Neuronal Networks) framework, which aims to facilitate the use of graphics accelerators for computational models of large-scale neuronal networks to address this challenge. GeNN is an open source library that generates code to accelerate the execution of network simulations on NVIDIA GPUs, through a flexible and extensible interface, which does not require in-depth technical knowledge from the users. We present performance benchmarks showing that 200-fold speedup compared to a single core of a CPU can be achieved for a network of one million conductance based Hodgkin-Huxley neurons but that for other models the speedup can differ. GeNN is available for Linux, Mac OS X and Windows platforms. The source code, user manual, tutorials, Wiki, in-depth example projects and all other related information can be found on the project website http://genn-team.github.io/genn/. PMID:26740369

Large-Scale NASA Science Applications on the Columbia Supercluster

NASA Technical Reports Server (NTRS)

Brooks, Walter

2005-01-01

Columbia, NASA's newest 61 teraflops supercomputer that became operational late last year, is a highly integrated Altix cluster of 10,240 processors, and was named to honor the crew of the Space Shuttle lost in early 2003. Constructed in just four months, Columbia increased NASA's computing capability ten-fold, and revitalized the Agency's high-end computing efforts. Significant cutting-edge science and engineering simulations in the areas of space and Earth sciences, as well as aeronautics and space operations, are already occurring on this largest operational Linux supercomputer, demonstrating its capacity and capability to accelerate NASA's space exploration vision. The presentation will describe how an integrated environment consisting not only of next-generation systems, but also modeling and simulation, high-speed networking, parallel performance optimization, and advanced data analysis and visualization, is being used to reduce design cycle time, accelerate scientific discovery, conduct parametric analysis of multiple scenarios, and enhance safety during the life cycle of NASA missions. The talk will conclude by discussing how NAS partnered with various NASA centers, other government agencies, computer industry, and academia, to create a national resource in large-scale modeling and simulation.

Subglottal pressure and fundamental frequency control in contact calls of juvenile Alligator mississippiensis

PubMed Central

Riede, Tobias; Tokuda, Isao T.; Farmer, C. G.

2011-01-01

SUMMARY Vocalization is rare among non-avian reptiles, with the exception of the crocodilians, the sister taxon of birds. Crocodilians have a complex vocal repertoire. Their vocal and respiratory system is not well understood but appears to consist of a combination of features that are also found in the extremely vocal avian and mammalian taxa. Anatomical studies suggest that the alligator larynx is able to abduct and adduct the vocal folds, but not to elongate or shorten them, and is therefore lacking a key regulator of frequency, yet alligators can modulate fundamental frequency remarkably well. We investigated the morphological and physiological features of sound production in alligators. Vocal fold length scales isometrically across a wide range of alligator body sizes. The relationship between fundamental frequency and subglottal pressure is significant in some individuals at some isolated points, such as call onset and position of maximum fundamental frequency. The relationship is not consistent over large segments of the call. Fundamental frequency can change faster than expected by pressure changes alone, suggesting an active motor pattern controls frequency and is intrinsic to the larynx. We utilized a two-mass vocal fold model to test whether abduction and adduction could generate this motor pattern. The fine-tuned interplay between subglottal pressure and glottal adduction can achieve frequency modulations much larger than those resulting from subglottal pressure variations alone and of similar magnitude, as observed in alligator calls. We conclude that the alligator larynx represents a sound source with only two control parameters (subglottal pressure and vocal fold adduction) in contrast to the mammalian larynx in which three parameters can be altered to modulate frequency (subglottal pressure, vocal fold adduction and length/tension). PMID:21865521

The Cenozoic fold-and-thrust belt of Eastern Sardinia: Evidences from the integration of field data with numerically balanced geological cross section

NASA Astrophysics Data System (ADS)

Arragoni, S.; Maggi, M.; Cianfarra, P.; Salvini, F.

2016-06-01

Newly collected structural data in Eastern Sardinia (Italy) integrated with numerical techniques led to the reconstruction of a 2-D admissible and balanced model revealing the presence of a widespread Cenozoic fold-and-thrust belt. The model was achieved with the FORC software, obtaining a 3-D (2-D + time) numerical reconstruction of the continuous evolution of the structure through time. The Mesozoic carbonate units of Eastern Sardinia and their basement present a fold-and-thrust tectonic setting, with a westward direction of tectonic transport (referred to the present-day coordinates). The tectonic style of the upper levels is thin skinned, with flat sectors prevailing over ramps and younger-on-older thrusts. Three regional tectonic units are present, bounded by two regional thrusts. Strike-slip faults overprint the fold-and-thrust belt and developed during the Sardinia-Corsica Block rotation along the strike of the preexisting fault ramps, not affecting the numerical section balancing. This fold-and-thrust belt represents the southward prosecution of the Alpine Corsica collisional chain and the missing link between the Alpine Chain and the Calabria-Peloritani Block. Relative ages relate its evolution to the meso-Alpine event (Eocene-Oligocene times), prior to the opening of the Tyrrhenian Sea (Tortonian). Results fill a gap of information about the geodynamic evolution of the European margin in Central Mediterranean, between Corsica and the Calabria-Peloritani Block, and imply the presence of remnants of this double-verging belt, missing in the Southern Tyrrhenian basin, within the Southern Apennine chain. The used methodology proved effective for constraining balanced cross sections also for areas lacking exposures of the large-scale structures, as the case of Eastern Sardinia.

Effects of environmental covariates and density on the catchability of fish populations and interpretation of catch per unit effort trends

USGS Publications Warehouse

Korman, Josh; Yard, Mike

2017-01-01

Article for outlet: Fisheries Research. Abstract: Quantifying temporal and spatial trends in abundance or relative abundance is required to evaluate effects of harvest and changes in habitat for exploited and endangered fish populations. In many cases, the proportion of the population or stock that is captured (catchability or capture probability) is unknown but is often assumed to be constant over space and time. We used data from a large-scale mark-recapture study to evaluate the extent of spatial and temporal variation, and the effects of fish density, fish size, and environmental covariates, on the capture probability of rainbow trout (Oncorhynchus mykiss) in the Colorado River, AZ. Estimates of capture probability for boat electrofishing varied 5-fold across five reaches, 2.8-fold across the range of fish densities that were encountered, 2.1-fold over 19 trips, and 1.6-fold over five fish size classes. Shoreline angle and turbidity were the best covariates explaining variation in capture probability across reaches and trips. Patterns in capture probability were driven by changes in gear efficiency and spatial aggregation, but the latter was more important. Failure to account for effects of fish density on capture probability when translating a historical catch per unit effort time series into a time series of abundance, led to 2.5-fold underestimation of the maximum extent of variation in abundance over the period of record, and resulted in unreliable estimates of relative change in critical years. Catch per unit effort surveys have utility for monitoring long-term trends in relative abundance, but are too imprecise and potentially biased to evaluate population response to habitat changes or to modest changes in fishing effort.

Proteome-level interplay between folding and aggregation propensities of proteins.

PubMed

Tartaglia, Gian Gaetano; Vendruscolo, Michele

2010-10-08

With the advent of proteomics, there is an increasing need of tools for predicting the properties of large numbers of proteins by using the information provided by their amino acid sequences, even in the absence of the knowledge of their structures. One of the most important types of predictions concerns whether proteins will fold or aggregate. Here, we study the competition between these two processes by analyzing the relationship between the folding and aggregation propensity profiles for the human and Escherichia coli proteomes. These profiles are calculated, respectively, using the CamFold method, which we introduce in this work, and the Zyggregator method. Our results indicate that the kinetic behavior of proteins is, to a large extent, determined by the interplay between regions of low folding and high aggregation propensities. Copyright © 2010. Published by Elsevier Ltd.

High Prevalence of Obesity, Hypertension, Hyperlipidemia, and Diabetes Mellitus in Japanese Outpatients with Schizophrenia: A Nationwide Survey

PubMed Central

Sugai, Takuro; Suzuki, Yutaro; Yamazaki, Manabu; Shimoda, Kazutaka; Mori, Takao; Ozeki, Yuji; Matsuda, Hiroshi; Sugawara, Norio; Yasui-Furukori, Norio; Minami, Yoshitake; Okamoto, Kurefu; Sagae, Toyoaki; Someya, Toshiyuki

2016-01-01

Background Patients with schizophrenia have significantly shorter life expectancy than the general population, and a problem they commonly face is an unhealthy lifestyle, which can lead to obesity and metabolic syndrome. There is a very clear need to determine the prevalence of obesity, hypertension, hyperlipidemia, and diabetes mellitus which are components of metabolic syndrome in patients with schizophrenia, but there has been a paucity of large-scale studies examining this situation in Japan. The aim of our study was to address this need. Setting & Participants We conducted a large-scale investigation of the prevalence of obesity, hypertension, hyperlipidemia, and diabetes mellitus using a questionnaire in 520 outpatient facilities and 247 inpatient facilities of the Japan Psychiatric Hospitals Association between January 2012 and July 2013. There were 7,655 outpatients and 15,461 inpatients with schizophrenia. Results The outpatients had significantly higher prevalence of obesity, hypertension, hypertriglyceridemia, hyper-LDL cholesterolemia, and diabetes mellitus than the inpatients. The prevalence of hypo-HDL cholesterolemia was higher in inpatients than outpatients. Age-specific analysis showed the prevalence of obesity, hypertension, hypertriglyceridemia, hyper-LDL cholesterolemia, and diabetes mellitus among outpatients to be 2- to 3-fold higher than among inpatients. In individuals aged ≥60 years, the prevalence of obesity and DM among outpatients was about 3-fold higher than among inpatients. Conclusion Japanese outpatients with schizophrenia were more likely to have physical risk such as obesity, hypertension, hyperlipidemia, and diabetes mellitus than inpatients. The physical risk to patients with schizophrenia may be affected by environmental parameters, such as type of care. The physical risk to Japanese patients with schizophrenia demands greater attention. PMID:27855222

High Prevalence of Obesity, Hypertension, Hyperlipidemia, and Diabetes Mellitus in Japanese Outpatients with Schizophrenia: A Nationwide Survey.

PubMed

Sugai, Takuro; Suzuki, Yutaro; Yamazaki, Manabu; Shimoda, Kazutaka; Mori, Takao; Ozeki, Yuji; Matsuda, Hiroshi; Sugawara, Norio; Yasui-Furukori, Norio; Minami, Yoshitake; Okamoto, Kurefu; Sagae, Toyoaki; Someya, Toshiyuki

2016-01-01

Patients with schizophrenia have significantly shorter life expectancy than the general population, and a problem they commonly face is an unhealthy lifestyle, which can lead to obesity and metabolic syndrome. There is a very clear need to determine the prevalence of obesity, hypertension, hyperlipidemia, and diabetes mellitus which are components of metabolic syndrome in patients with schizophrenia, but there has been a paucity of large-scale studies examining this situation in Japan. The aim of our study was to address this need. We conducted a large-scale investigation of the prevalence of obesity, hypertension, hyperlipidemia, and diabetes mellitus using a questionnaire in 520 outpatient facilities and 247 inpatient facilities of the Japan Psychiatric Hospitals Association between January 2012 and July 2013. There were 7,655 outpatients and 15,461 inpatients with schizophrenia. The outpatients had significantly higher prevalence of obesity, hypertension, hypertriglyceridemia, hyper-LDL cholesterolemia, and diabetes mellitus than the inpatients. The prevalence of hypo-HDL cholesterolemia was higher in inpatients than outpatients. Age-specific analysis showed the prevalence of obesity, hypertension, hypertriglyceridemia, hyper-LDL cholesterolemia, and diabetes mellitus among outpatients to be 2- to 3-fold higher than among inpatients. In individuals aged ≥60 years, the prevalence of obesity and DM among outpatients was about 3-fold higher than among inpatients. Japanese outpatients with schizophrenia were more likely to have physical risk such as obesity, hypertension, hyperlipidemia, and diabetes mellitus than inpatients. The physical risk to patients with schizophrenia may be affected by environmental parameters, such as type of care. The physical risk to Japanese patients with schizophrenia demands greater attention.

Comparison of evidence on harms of medical interventions in randomized and nonrandomized studies

PubMed Central

Papanikolaou, Panagiotis N.; Christidi, Georgia D.; Ioannidis, John P.A.

2006-01-01

Background Information on major harms of medical interventions comes primarily from epidemiologic studies performed after licensing and marketing. Comparison with data from large-scale randomized trials is occasionally feasible. We compared evidence from randomized trials with that from epidemiologic studies to determine whether they give different estimates of risk for important harms of medical interventions. Methods We targeted well-defined, specific harms of various medical interventions for which data were already available from large-scale randomized trials (> 4000 subjects). Nonrandomized studies involving at least 4000 subjects addressing these same harms were retrieved through a search of MEDLINE. We compared the relative risks and absolute risk differences for specific harms in the randomized and nonrandomized studies. Results Eligible nonrandomized studies were found for 15 harms for which data were available from randomized trials addressing the same harms. Comparisons of relative risks between the study types were feasible for 13 of the 15 topics, and of absolute risk differences for 8 topics. The estimated increase in relative risk differed more than 2-fold between the randomized and nonrandomized studies for 7 (54%) of the 13 topics; the estimated increase in absolute risk differed more than 2-fold for 5 (62%) of the 8 topics. There was no clear predilection for randomized or nonrandomized studies to estimate greater relative risks, but usually (75% [6/8]) the randomized trials estimated larger absolute excess risks of harm than the nonrandomized studies did. Interpretation Nonrandomized studies are often conservative in estimating absolute risks of harms. It would be useful to compare and scrutinize the evidence on harms obtained from both randomized and nonrandomized studies. PMID:16505459

Segmental Duplications and Copy-Number Variation in the Human Genome

PubMed Central

Sharp, Andrew J. ; Locke, Devin P. ; McGrath, Sean D. ; Cheng, Ze ; Bailey, Jeffrey A. ; Vallente, Rhea U. ; Pertz, Lisa M. ; Clark, Royden A. ; Schwartz, Stuart ; Segraves, Rick ; Oseroff, Vanessa V. ; Albertson, Donna G. ; Pinkel, Daniel ; Eichler, Evan E. 

2005-01-01

The human genome contains numerous blocks of highly homologous duplicated sequence. This higher-order architecture provides a substrate for recombination and recurrent chromosomal rearrangement associated with genomic disease. However, an assessment of the role of segmental duplications in normal variation has not yet been made. On the basis of the duplication architecture of the human genome, we defined a set of 130 potential rearrangement hotspots and constructed a targeted bacterial artificial chromosome (BAC) microarray (with 2,194 BACs) to assess copy-number variation in these regions by array comparative genomic hybridization. Using our segmental duplication BAC microarray, we screened a panel of 47 normal individuals, who represented populations from four continents, and we identified 119 regions of copy-number polymorphism (CNP), 73 of which were previously unreported. We observed an equal frequency of duplications and deletions, as well as a 4-fold enrichment of CNPs within hotspot regions, compared with control BACs (P < .000001), which suggests that segmental duplications are a major catalyst of large-scale variation in the human genome. Importantly, segmental duplications themselves were also significantly enriched >4-fold within regions of CNP. Almost without exception, CNPs were not confined to a single population, suggesting that these either are recurrent events, having occurred independently in multiple founders, or were present in early human populations. Our study demonstrates that segmental duplications define hotspots of chromosomal rearrangement, likely acting as mediators of normal variation as well as genomic disease, and it suggests that the consideration of genomic architecture can significantly improve the ascertainment of large-scale rearrangements. Our specialized segmental duplication BAC microarray and associated database of structural polymorphisms will provide an important resource for the future characterization of human genomic disorders. PMID:15918152

Fault propagation folds induced by gravitational failure and slumping of the Central Costa Rica volcanic range: Implications for large terrestrial and Martian volcanic edifices

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

Borgia, A.; Burr, J.; Montero, W.

1990-08-30

Long sublinear ridges and related scarps located at the base of large volcanic structures are frequently interpreted as normal faults associated with extensional regional stress. In contrast, the ridges bordering the Central Costa Rica volcanic range (CCRVR) are the topographic expression of hanging wall asymmetric angular anticlines overlying low-angle thrust faults at the base of the range. These faults formed by gravitational failure and slumping of the flanks of the range due to the weight of the volcanic edifices and were perhaps triggered by the intrusion of magma over the past 20,000 years. These anticlines are hypothesized to occur alongmore » the base of the volcano, where the thrust faults ramp up toward the sea bottom. Ridges and scarps between 2,000 and 5,000 m below sea level are interpreted as the topographic expression of these folds. The authors further suggest that the scarps of the CCRVR and valid scaled terrestrial analogs of the perimeter scarp of the Martian volcano Olympus Mons. They suggest that the crust below Olympus Mons has failed under the load of the volcano, triggering the radial slumping of the flanks of the volcano on basal thrusts. The thrusting would have, in turn, formed the anticlinal ridges and scarps that surround the edifice. The thrust faults may extend all the way to the base of the Martian crust (about 40 km), and they may have been active until almost the end of the volcanic activity. They suggest that gravitational failure and slumping of the flanks of volcanoes is a process common to most large volcanic edifices. In the CCRVR this slumping of the flanks is a slow intermittent process, but it could evolve to rapid massive avalanching leading to catastrophic eruptions. Thus monitoring of uplift and displacement of the folds related to the slump tectonics could become an additional effective method for mitigating volcanic hazards.« less

Curvature, metric and parametrization of origami tessellations: theory and application to the eggbox pattern.

PubMed

Nassar, H; Lebée, A; Monasse, L

2017-01-01

Origami tessellations are particular textured morphing shell structures. Their unique folding and unfolding mechanisms on a local scale aggregate and bring on large changes in shape, curvature and elongation on a global scale. The existence of these global deformation modes allows for origami tessellations to fit non-trivial surfaces thus inspiring applications across a wide range of domains including structural engineering, architectural design and aerospace engineering. The present paper suggests a homogenization-type two-scale asymptotic method which, combined with standard tools from differential geometry of surfaces, yields a macroscopic continuous characterization of the global deformation modes of origami tessellations and other similar periodic pin-jointed trusses. The outcome of the method is a set of nonlinear differential equations governing the parametrization, metric and curvature of surfaces that the initially discrete structure can fit. The theory is presented through a case study of a fairly generic example: the eggbox pattern. The proposed continuous model predicts correctly the existence of various fittings that are subsequently constructed and illustrated.

Curvature, metric and parametrization of origami tessellations: theory and application to the eggbox pattern

NASA Astrophysics Data System (ADS)

Nassar, H.; Lebée, A.; Monasse, L.

2017-01-01

Origami tessellations are particular textured morphing shell structures. Their unique folding and unfolding mechanisms on a local scale aggregate and bring on large changes in shape, curvature and elongation on a global scale. The existence of these global deformation modes allows for origami tessellations to fit non-trivial surfaces thus inspiring applications across a wide range of domains including structural engineering, architectural design and aerospace engineering. The present paper suggests a homogenization-type two-scale asymptotic method which, combined with standard tools from differential geometry of surfaces, yields a macroscopic continuous characterization of the global deformation modes of origami tessellations and other similar periodic pin-jointed trusses. The outcome of the method is a set of nonlinear differential equations governing the parametrization, metric and curvature of surfaces that the initially discrete structure can fit. The theory is presented through a case study of a fairly generic example: the eggbox pattern. The proposed continuous model predicts correctly the existence of various fittings that are subsequently constructed and illustrated.

A method for estimating 2D Wrinkle Ridge Strain from application of fault displacement scaling to the Yakima Folds, Washington

NASA Astrophysics Data System (ADS)

Mège, Daniel; Reidel, Stephen P.

The Yakima folds on the central Columbia Plateau are a succession of thrusted anticlines thought to be analogs of planetary wrinkle ridges. They provide a unique opportunity to understand wrinkle ridge structure. Field data and length-displacement scaling are used to demonstrate a method for estimating two-dimensional horizontal contractional strain at wrinkle ridges. Strain is given as a function of ridge length, and depends on other parameters that can be inferred from the Yakima folds and fault population displacement studies. Because ridge length can be readily obtained from orbital imagery, the method can be applied to any wrinkle ridge population, and helps constrain quantitative tectonic models on other planets.

Stem cell motility enables a density-dependent rate of fate commitment during scaled resizing of adult organs

NASA Astrophysics Data System (ADS)

Du, Xinxin; O'Brien, Lucy; Riedel-Kruse, Ingmar

Many adult organs grow or shrink to accommodate fluctuating levels of physiological demand. Specifically, the intestine of the fruit fly (the midgut) expands four-fold in the number of mature cells and, proportionally, the number of stem cells when the fly eats. However, the cellular behaviors that give rise to this stem scaling are not well-understood. Here we present a biophysical model of the adult fly midgut. A set of differential equations can recapitulate the physiological kinetics of cells during midgut growth and shrinkage as long as the rate of stem cell fate commitment depends on the stem cell number density in the tissue. To elucidate the source of this dependence, we model the tissue in a 2D simulation with soft spheres, where stem cells choose fate commitment through Delta-Notch pathway interactions with other stem cells, a known process in fly midguts. We find that as long as stem cells exhibit a large enough amplitude of random motion through the tissue (`stem cell motility'), and explore a large enough `territory' in their lifetime, stem cell scaling can occur. These model observations are confirmed through in vivo live-imaging, where we indeed see that stem cells are motile in the fly midgut.

Mechanical development of folded chert beds in Monterey Formation, California

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

Crowther, D.; Snyder, W.S.

1988-03-01

Small-scale folds in the upper siliceous facies of the Miocene Monterey Formation, at Lions Head, California (Santa Maria basin) are of tectonic origin. Folding is well developed in the chert-dominated zones and dies out rapidly in the adjacent siliceous mudstones. A tectonic origin is evidenced by the dominantly brittle deformation of the competent chert layers. Mechanically, the folds formed through a complex interrelationship between fracture and flexural slip. Opal-CT and quartz-chert layers display brittle fractures and rotated fracture blocks that responded to shortening. Thrusting of the chert layers is common in folds where fold propagation was impeded. Dilation breccia andmore » void space occur in the hinges and reflect room problems during development of these disharmonic folds. Subsequent diagenesis has partially healed the fractures and slip surfaces, creating the erroneous appearance that ductile deformation was an important factor in the formation of the folds.« less

An Evolution-Based Approach to De Novo Protein Design and Case Study on Mycobacterium tuberculosis

PubMed Central

Brender, Jeffrey R.; Czajka, Jeff; Marsh, David; Gray, Felicia; Cierpicki, Tomasz; Zhang, Yang

2013-01-01

Computational protein design is a reverse procedure of protein folding and structure prediction, where constructing structures from evolutionarily related proteins has been demonstrated to be the most reliable method for protein 3-dimensional structure prediction. Following this spirit, we developed a novel method to design new protein sequences based on evolutionarily related protein families. For a given target structure, a set of proteins having similar fold are identified from the PDB library by structural alignments. A structural profile is then constructed from the protein templates and used to guide the conformational search of amino acid sequence space, where physicochemical packing is accommodated by single-sequence based solvation, torsion angle, and secondary structure predictions. The method was tested on a computational folding experiment based on a large set of 87 protein structures covering different fold classes, which showed that the evolution-based design significantly enhances the foldability and biological functionality of the designed sequences compared to the traditional physics-based force field methods. Without using homologous proteins, the designed sequences can be folded with an average root-mean-square-deviation of 2.1 Å to the target. As a case study, the method is extended to redesign all 243 structurally resolved proteins in the pathogenic bacteria Mycobacterium tuberculosis, which is the second leading cause of death from infectious disease. On a smaller scale, five sequences were randomly selected from the design pool and subjected to experimental validation. The results showed that all the designed proteins are soluble with distinct secondary structure and three have well ordered tertiary structure, as demonstrated by circular dichroism and NMR spectroscopy. Together, these results demonstrate a new avenue in computational protein design that uses knowledge of evolutionary conservation from protein structural families to engineer new protein molecules of improved fold stability and biological functionality. PMID:24204234

SVM-Fold: a tool for discriminative multi-class protein fold and superfamily recognition

PubMed Central

Melvin, Iain; Ie, Eugene; Kuang, Rui; Weston, Jason; Stafford, William Noble; Leslie, Christina

2007-01-01

Background Predicting a protein's structural class from its amino acid sequence is a fundamental problem in computational biology. Much recent work has focused on developing new representations for protein sequences, called string kernels, for use with support vector machine (SVM) classifiers. However, while some of these approaches exhibit state-of-the-art performance at the binary protein classification problem, i.e. discriminating between a particular protein class and all other classes, few of these studies have addressed the real problem of multi-class superfamily or fold recognition. Moreover, there are only limited software tools and systems for SVM-based protein classification available to the bioinformatics community. Results We present a new multi-class SVM-based protein fold and superfamily recognition system and web server called SVM-Fold, which can be found at . Our system uses an efficient implementation of a state-of-the-art string kernel for sequence profiles, called the profile kernel, where the underlying feature representation is a histogram of inexact matching k-mer frequencies. We also employ a novel machine learning approach to solve the difficult multi-class problem of classifying a sequence of amino acids into one of many known protein structural classes. Binary one-vs-the-rest SVM classifiers that are trained to recognize individual structural classes yield prediction scores that are not comparable, so that standard "one-vs-all" classification fails to perform well. Moreover, SVMs for classes at different levels of the protein structural hierarchy may make useful predictions, but one-vs-all does not try to combine these multiple predictions. To deal with these problems, our method learns relative weights between one-vs-the-rest classifiers and encodes information about the protein structural hierarchy for multi-class prediction. In large-scale benchmark results based on the SCOP database, our code weighting approach significantly improves on the standard one-vs-all method for both the superfamily and fold prediction in the remote homology setting and on the fold recognition problem. Moreover, our code weight learning algorithm strongly outperforms nearest-neighbor methods based on PSI-BLAST in terms of prediction accuracy on every structure classification problem we consider. Conclusion By combining state-of-the-art SVM kernel methods with a novel multi-class algorithm, the SVM-Fold system delivers efficient and accurate protein fold and superfamily recognition. PMID:17570145

Large-scale manufacturing of GMP-compliant anti-EGFR targeted nanocarriers: production of doxorubicin-loaded anti-EGFR-immunoliposomes for a first-in-man clinical trial.

PubMed

Wicki, Andreas; Ritschard, Reto; Loesch, Uli; Deuster, Stefanie; Rochlitz, Christoph; Mamot, Christoph

2015-04-30

We describe the large-scale, GMP-compliant production process of doxorubicin-loaded and anti-EGFR-coated immunoliposomes (anti-EGFR-ILs-dox) used in a first-in-man, dose escalation clinical trial. 10 batches of this nanoparticle have been produced in clean room facilities. Stability data from the pre-GMP and the GMP batch indicate that the anti-EGFR-ILs-dox nanoparticle was stable for at least 18 months after release. Release criteria included visual inspection, sterility testing, as well as measurements of pH (pH 5.0-7.0), doxorubicin HCl concentration (0.45-0.55 mg/ml), endotoxin concentration (<1.21 IU/ml), leakage (<10%), particle size (Z-average of Caelyx ± 20 nm), and particle uptake (uptake absolute: >0.50 ng doxorubicin/μg protein; uptake relatively to PLD: >5 fold). All batches fulfilled the defined release criteria, indicating a high reproducibility as well as batch-to-batch uniformity of the main physico-chemical features of the nanoparticles in the setting of the large-scale GMP process. In the clinical trial, 29 patients were treated with this nanoparticle between 2007 and 2010. Pharmacokinetic data of anti-EGFR-ILs-dox collected during the clinical study revealed stability of the nanocarrier in vivo. Thus, reliable and GMP-compliant production of anti-EGFR-targeted nanoparticles for clinical application is feasible. Copyright © 2015 Elsevier B.V. All rights reserved.

Towards Scalable Deep Learning via I/O Analysis and Optimization

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

Pumma, Sarunya; Si, Min; Feng, Wu-Chun

Deep learning systems have been growing in prominence as a way to automatically characterize objects, trends, and anomalies. Given the importance of deep learning systems, researchers have been investigating techniques to optimize such systems. An area of particular interest has been using large supercomputing systems to quickly generate effective deep learning networks: a phase often referred to as “training” of the deep learning neural network. As we scale existing deep learning frameworks—such as Caffe—on these large supercomputing systems, we notice that the parallelism can help improve the computation tremendously, leaving data I/O as the major bottleneck limiting the overall systemmore » scalability. In this paper, we first present a detailed analysis of the performance bottlenecks of Caffe on large supercomputing systems. Our analysis shows that the I/O subsystem of Caffe—LMDB—relies on memory-mapped I/O to access its database, which can be highly inefficient on large-scale systems because of its interaction with the process scheduling system and the network-based parallel filesystem. Based on this analysis, we then present LMDBIO, our optimized I/O plugin for Caffe that takes into account the data access pattern of Caffe in order to vastly improve I/O performance. Our experimental results show that LMDBIO can improve the overall execution time of Caffe by nearly 20-fold in some cases.« less

Ground Motion Simulation for a Large Active Fault System using Empirical Green's Function Method and the Strong Motion Prediction Recipe - a Case Study of the Noubi Fault Zone -

NASA Astrophysics Data System (ADS)

Kuriyama, M.; Kumamoto, T.; Fujita, M.

2005-12-01

The 1995 Hyogo-ken Nambu Earthquake (1995) near Kobe, Japan, spurred research on strong motion prediction. To mitigate damage caused by large earthquakes, a highly precise method of predicting future strong motion waveforms is required. In this study, we applied empirical Green's function method to forward modeling in order to simulate strong ground motion in the Noubi Fault zone and examine issues related to strong motion prediction for large faults. Source models for the scenario earthquakes were constructed using the recipe of strong motion prediction (Irikura and Miyake, 2001; Irikura et al., 2003). To calculate the asperity area ratio of a large fault zone, the results of a scaling model, a scaling model with 22% asperity by area, and a cascade model were compared, and several rupture points and segmentation parameters were examined for certain cases. A small earthquake (Mw: 4.6) that occurred in northern Fukui Prefecture in 2004 were examined as empirical Green's function, and the source spectrum of this small event was found to agree with the omega-square scaling law. The Nukumi, Neodani, and Umehara segments of the 1891 Noubi Earthquake were targeted in the present study. The positions of the asperity area and rupture starting points were based on the horizontal displacement distributions reported by Matsuda (1974) and the fault branching pattern and rupture direction model proposed by Nakata and Goto (1998). Asymmetry in the damage maps for the Noubi Earthquake was then examined. We compared the maximum horizontal velocities for each case that had a different rupture starting point. In the case, rupture started at the center of the Nukumi Fault, while in another case, rupture started on the southeastern edge of the Umehara Fault; the scaling model showed an approximately 2.1-fold difference between these cases at observation point FKI005 of K-Net. This difference is considered to relate to the directivity effect associated with the direction of rupture propagation. Moreover, it was clarified that the horizontal velocities by assuming the cascade model was underestimated more than one standard deviation of empirical relation by Si and Midorikawa (1999). The scaling and cascade models showed an approximately 6.4-fold difference for the case, in which the rupture started along the southeastern edge of the Umehara Fault at observation point GIF020. This difference is significantly large in comparison with the effect of different rupture starting points, and shows that it is important to base scenario earthquake assumptions on active fault datasets before establishing the source characterization model. The distribution map of seismic intensity for the 1891 Noubi Earthquake also suggests that the synthetic waveforms in the southeastern Noubi Fault zone may be underestimated. Our results indicate that outer fault parameters (e.g., earthquake moment) related to the construction of scenario earthquakes influence strong motion prediction, rather than inner fault parameters such as the rupture starting point. Based on these methods, we will predict strong motion for approximately 140 to 150 km of the Itoigawa-Shizuoka Tectonic Line.

Evidence for fourth generation structures in the Piedra Lumbre region, Western Picuris Mountains, New Mexico

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

Chernoff, C.B.; Helper, M.A.; Mosher, S.

1993-02-01

Mid-Proterozoic Hondo Group metasediments in the western Picuris Mountains, New Mexico clearly display 3 generations of previously recognized penetrative, synmetamorphic structures and a previously undocumented forth generation of overprinting folds with an associated axial planar foliation. The earliest structures include: (1) a bedding-parallel S[sub 1] foliation and rare, rootless, intrafolial F[sub 1] folds; (2) north-verging, west-trending F[sub 2] folds and an axial planar metamorphic foliation (S[sub 2]); (3) a steeply dipping, N-S striking crenulation cleavage (S[sub 3]). In the Piedra Lumbre region, southwest-plunging, open, upright chevron and box folds (F[sub 4]) locally reorient F[sub 2], S[sub 2] and S[sub 3]more » crenulations. The largest F[sub 4] folds in the Piedra Lumbre region have half-wavelengths of 500 meters. An associated nearly vertical foliation (S[sub 4]) overprints the first three foliations. The S[sub 4] foliation is a crenulation cleavage in micaceous layers and a discontinuous alignment of biotite laths in quartzose layers. Crystallization of biotite during S[sub 4] and chloritoid after S[sub 4], along with static recrystallization and mineral replacement by chlorite, suggests this deformation occurred during the waning stages of mid-Proterozoic metamorphism. The orientation of F[sub 2] and F[sub 4] folds are similar and both appear to occur on a regional scale. Interference of open upright F[sub 4] folds and tight, north-verging, overturned F[sub 2] folds produces a geometry that resembles that of the kilometer-scale Copper Hill Anticline of the western Picuris Mountains, previously interpreted to be solely the result of F[sub 2] folding.« less

2D numerical modeling of gravity-driven giant-scale deformation processes in the offshore Barreirinhas Basin (Brazil)

NASA Astrophysics Data System (ADS)

Cruciani, Francesco; Manconi, Andrea; Rinaldo Barchi, Massimiliano

2014-05-01

Gravity-driven deformation processes at continental passive margins occur at different scales, from small-scale turbidity currents and sediment slides, to large-scale mass transport complexes (MTCs), to the giant-scale deep water fold and thrust belts (DW-FTBs), which affect most or the entire sedimentary sequence. This kind of giant structures, quite widespread in passive margins, may be active for tens of millions of years. In this context, the Brazilian Atlantic margin hosts several well-known DW-FTBs detached on both shale and salt décollement. Despite of their relevant scientific and economic importance, the mechanical processes driving the onset and evolution of these giant-scale structures are still poorly investigated. In this work, we focus on the shale décollement DW-FTB of the Barreirinhas Basin, where the continental slope has been affected by multi-phase gravitational processes since the Late Cretaceous. This DW-FTB consists of a linked fault system of listric normal faults updip and thrust faults downdip, detached over a common concave upward décollement surface. From the onshore extensional to the offshore compressional domain the DW-FTB is about 50 km wide and involve a sedimentary sequence up to 5 km thick. Shortening within the compressional domain is accommodated almost entirely from a single thrust ramp with a large related anticline fold. Previous studies have shown that the main activity phases of the gravitational processes are closely linked to significant increases in the sediment supply within the basin. Indeed, the highest deformation rate, accounting for about 80% of the net strain, occurred in the Upper Miocene following a drainage rearrangement which led to the birth of the modern Amazon River drainage system. The Barreirinhas Basin DW-FTB entails a rather simple geometrical structure, which can be well schematized, therefore is particularly suitable for numerical simulations aimed to study and understand the dynamics of DW-FTB at this particular place and also elsewhere. We set up a 2D fluid dynamic model by considering a Finite Element Method (FEM) environment, which allows us to well represent the geometries, densities and viscosities of the geological materials, as derived from geophysical investigations. Our study aims at understanding whether the long-term mechanical behavior of the Barreirinhas Basin DW-FTB can be reproduced by considering a simplified Newtonian fluid dynamics environment or it is controlled by a more complex rheology, which might include the effect of additional parameters such as internal friction, cohesive strength and pore-fluid pressure at the basal detachment.

Inflation with Whip-Shaped Suppressed Scalar Power Spectra

NASA Astrophysics Data System (ADS)

Hazra, Dhiraj Kumar; Shafieloo, Arman; Smoot, George F.; Starobinsky, Alexei A.

2014-08-01

Motivated by the idea that inflation occurs at the grand unified theory symmetry breaking scale, in this Letter we construct a new class of large field inflaton potentials where the inflaton starts with a power law potential; after an initial period of relatively fast roll that lasts until after a few e folds inside the horizon it transits to the attractor of the slow roll part of the potential with a lower power. Because of the initial fast roll stages of inflation, we find a suppression in scalar primordial power at large scales and at the same time the choice of the potential can provide us a tensor primordial spectrum with a high amplitude. This suppression in scalar power with a large tensor-to-scalar ratio helps us to reconcile the Planck and BICEP2 data in a single framework. We find that a transition from a cubic to quadratic form of inflaton potential generates an appropriate suppression in the power of the scalar primordial spectrum that provides a significant improvement in fit compared to the power law model when compared with Planck and BICEP2 data together. We calculate the extent of non-Gaussianity, specifically, the bispectrum for the best fit potential, and show that it is consistent with Planck bispectrum constraints.

Predicting origami-inspired programmable self-folding of hydrogel trilayers

NASA Astrophysics Data System (ADS)

An, Ning; Li, Meie; Zhou, Jinxiong

2016-11-01

Imitating origami principles in active or programmable materials opens the door for development of origami-inspired self-folding structures for not only aesthetic but also functional purposes. A variety of programmable materials enabled self-folding structures have been demonstrated across various fields and scales. These folding structures have finite thickness and the mechanical properties of the active materials dictate the folding process. Yet formalizing the use of origami rules for use in computer modeling has been challenging, owing to the zero-thickness theory and the exclusion of mechanical properties in current models. Here, we describe a physics-based finite element simulation scheme to predict programmable self-folding of temperature-sensitive hydrogel trilayers. Patterning crease and assigning mountain or valley folds are highlighted for complex origami such as folding of the Randlett’s flapping bird and the crane. Our efforts enhance the understanding and facilitate the design of origami-inspired self-folding structures, broadening the realization and application of reconfigurable structures.

Lessons from making the Structural Classification of Proteins (SCOP) and their implications for protein structure modelling.

PubMed

Andreeva, Antonina

2016-06-15

The Structural Classification of Proteins (SCOP) database has facilitated the development of many tools and algorithms and it has been successfully used in protein structure prediction and large-scale genome annotations. During the development of SCOP, numerous exceptions were found to topological rules, along with complex evolutionary scenarios and peculiarities in proteins including the ability to fold into alternative structures. This article reviews cases of structural variations observed for individual proteins and among groups of homologues, knowledge of which is essential for protein structure modelling. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Features from the non-attractor beginning of inflation

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

Cai, Yi-Fu; Wang, Dong-Gang; Wang, Ziwei

2016-10-01

We study the effects of the non-attractor initial conditions for the canonical single-field inflation. The non-attractor stage can last only several e -folding numbers, and should be followed by hilltop inflation. This two-stage evolution leads to large scale suppression in the primordial power spectrum, which is favored by recent observations. Moreover we give a detailed calculation of primordial non-Gaussianity due to the ''from non-attractor to slow-roll'' transition, and find step features in the local and equilateral shapes. We conclude that a plateau-like inflaton potential with an initial non-attractor phase yields interesting features in both power spectrum and bispectrum.

Strain development and kinematic significance of the Alpine folding on Andros (western Cyclades, Greece)

NASA Astrophysics Data System (ADS)

Ziv, A.; Katzir, Y.; Avigad, D.; Garfunkel, Z.

2010-06-01

The general trend of both fold axes and stretching lineation in the Cycladic Blueschist Unit is NE-SW to NNE-SSW. This orientation forms a large angle (almost perpendicular) with respect to the Hellenic trend that is inferred from the main thrusts on mainland Greece. Thus, the kinematic significance of the stretching parallel folding in the Cycladic Blueschist Unit is non-trivial. Since within the western Cyclades, the NE-trending folds are best exposed on the island of Andros, it is a key locality for understanding the timing, style and kinematic significance of folding. Here we show that the NE-trending folds on Andros formed within the stability field of glaucophane, after the peak high-pressure metamorphism and simultaneously with the early stage of retrogression. The axes-parallel stretching was non-rotational; it started during the NE folding at blueschist-facies conditions, and continued long afterward and well into the retrograde greenschist overprint. Furthermore, we present the result of a finite strain calculation which shows that the large NE folds could not have been reoriented at ~ 90° as previously thought. Instead it is suggested that these folds formed under constrictional strain regime during regional NE-SW extension, and represent coeval transverse NW-SE shortening and vertical thinning. This implies that NE extension and southwest directed rollback of the active margin prevailed in the western Aegean between the Eocene and early Miocene.

Picosecond to nanosecond dynamics provide a source of conformational entropy for protein folding.

PubMed

Stadler, Andreas M; Demmel, Franz; Ollivier, Jacques; Seydel, Tilo

2016-08-03

Myoglobin can be trapped in fully folded structures, partially folded molten globules, and unfolded states under stable equilibrium conditions. Here, we report an experimental study on the conformational dynamics of different folded conformational states of apo- and holomyoglobin in solution. Global protein diffusion and internal molecular motions were probed by neutron time-of-flight and neutron backscattering spectroscopy on the picosecond and nanosecond time scales. Global protein diffusion was found to depend on the α-helical content of the protein suggesting that charges on the macromolecule increase the short-time diffusion of protein. With regard to the molten globules, a gel-like phase due to protein entanglement and interactions with neighbouring macromolecules was visible due to a reduction of the global diffusion coefficients on the nanosecond time scale. Diffusion coefficients, residence and relaxation times of internal protein dynamics and root mean square displacements of localised internal motions were determined for the investigated structural states. The difference in conformational entropy ΔSconf of the protein between the unfolded and the partially or fully folded conformations was extracted from the measured root mean square displacements. Using thermodynamic parameters from the literature and the experimentally determined ΔSconf values we could identify the entropic contribution of the hydration shell ΔShydr of the different folded states. Our results point out the relevance of conformational entropy of the protein and the hydration shell for stability and folding of myoglobin.

Slow roll during the waterfall regime: The small coupling window for supersymmetric hybrid inflation

NASA Astrophysics Data System (ADS)

Clesse, Sébastien; Garbrecht, Björn

2012-07-01

It has recently been pointed out that a substantial amount of e-folds can occur during the waterfall regime of hybrid inflation. Moreover, Kodama et al. have derived analytic approximations for the trajectories of the inflaton and of the waterfall fields. Based on these, we derive here the consequences for F- and D-term supersymmetric hybrid inflation: a substantial amount of e-folds may occur in the waterfall regime, provided κ≪M2/MP2, where κ is the superpotential coupling, M the scale of symmetry breaking and MP the reduced Planck mass. When this condition is amply fulfilled, a number of e-folds much larger than Ne≈60 can occur in the waterfall regime and the scalar spectral index is then given by the expression found by Kodama et al. ns=1-4/Ne. This value may be increased up to unity, if only about Ne e-folds occur during the waterfall regime, such that the largest observable scale leaves the horizon close to the critical point of hybrid inflation, what can be achieved for κ≈10-13 and M≈5×1012GeV in F-term inflation. Imposing the normalization of the power spectrum leads to a lower bound on the scale of symmetry breaking.

Vocal fold tissue failure: preliminary data and constitutive modeling.

PubMed

Chan, Roger W; Siegmund, Thomas

2004-08-01

In human voice production (phonation), linear small-amplitude vocal fold oscillation occurs only under restricted conditions. Physiologically, phonation more often involves large-amplitude oscillation associated with tissue stresses and strains beyond their linear viscoelastic limits, particularly in the lamina propria extracellular matrix (ECM). This study reports some preliminary measurements of tissue deformation and failure response of the vocal fold ECM under large-strain shear The primary goal was to formulate and test a novel constitutive model for vocal fold tissue failure, based on a standard-linear cohesive-zone (SL-CZ) approach. Tissue specimens of the sheep vocal fold mucosa were subjected to torsional deformation in vitro, at constant strain rates corresponding to twist rates of 0.01, 0.1, and 1.0 rad/s. The vocal fold ECM demonstrated nonlinear stress-strain and rate-dependent failure response with a failure strain as low as 0.40 rad. A finite-element implementation of the SL-CZ model was capable of capturing the rate dependence in these preliminary data, demonstrating the model's potential for describing tissue failure. Further studies with additional tissue specimens and model improvements are needed to better understand vocal fold tissue failure.

How Well Does a Funneled Energy Landscape Capture the Folding Mechanism of Spectrin Domains?

PubMed Central

2013-01-01

Three structurally similar domains from α-spectrin have been shown to fold very differently. Firstly, there is a contrast in the folding mechanism, as probed by Φ-value analysis, between the R15 domain and the R16 and R17 domains. Secondly, there are very different contributions from internal friction to folding: the folding rate of the R15 domain was found to be inversely proportional to solvent viscosity, showing no apparent frictional contribution from the protein, but in the other two domains a large internal friction component was evident. Non-native misdocking of helices has been suggested to be responsible for this phenomenon. Here, I study the folding of these three proteins with minimalist coarse-grained models based on a funneled energy landscape. Remarkably, I find that, despite the absence of non-native interactions, the differences in folding mechanism of the domains are well captured by the model, and the agreement of the Φ-values with experiment is fairly good. On the other hand, within the context of this model, there are no significant differences in diffusion coefficient along the chosen folding coordinate, and the model cannot explain the large differences in folding rates between the proteins found experimentally. These results are nonetheless consistent with the expectations from the energy landscape perspective of protein folding: namely, that the folding mechanism is primarily determined by the native-like interactions present in the Gō-like model, with missing non-native interactions being required to explain the differences in “internal friction” seen in experiment. PMID:23947368

Scaling-up NLP Pipelines to Process Large Corpora of Clinical Notes.

PubMed

Divita, G; Carter, M; Redd, A; Zeng, Q; Gupta, K; Trautner, B; Samore, M; Gundlapalli, A

2015-01-01

This article is part of the Focus Theme of Methods of Information in Medicine on "Big Data and Analytics in Healthcare". This paper describes the scale-up efforts at the VA Salt Lake City Health Care System to address processing large corpora of clinical notes through a natural language processing (NLP) pipeline. The use case described is a current project focused on detecting the presence of an indwelling urinary catheter in hospitalized patients and subsequent catheter-associated urinary tract infections. An NLP algorithm using v3NLP was developed to detect the presence of an indwelling urinary catheter in hospitalized patients. The algorithm was tested on a small corpus of notes on patients for whom the presence or absence of a catheter was already known (reference standard). In planning for a scale-up, we estimated that the original algorithm would have taken 2.4 days to run on a larger corpus of notes for this project (550,000 notes), and 27 days for a corpus of 6 million records representative of a national sample of notes. We approached scaling-up NLP pipelines through three techniques: pipeline replication via multi-threading, intra-annotator threading for tasks that can be further decomposed, and remote annotator services which enable annotator scale-out. The scale-up resulted in reducing the average time to process a record from 206 milliseconds to 17 milliseconds or a 12- fold increase in performance when applied to a corpus of 550,000 notes. Purposely simplistic in nature, these scale-up efforts are the straight forward evolution from small scale NLP processing to larger scale extraction without incurring associated complexities that are inherited by the use of the underlying UIMA framework. These efforts represent generalizable and widely applicable techniques that will aid other computationally complex NLP pipelines that are of need to be scaled out for processing and analyzing big data.

Clustering fossil from primordial gravitational waves in anisotropic inflation

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

Emami, Razieh; Firouzjahi, Hassan, E-mail: emami@ipm.ir, E-mail: firouz@ipm.ir

2015-10-01

Inflationary models can correlate small-scale density perturbations with the long-wavelength gravitational waves (GW) in the form of the Tensor-Scalar-Scalar (TSS) bispectrum. This correlation affects the mass-distribution in the Universe and leads to the off-diagonal correlations of the density field modes in the form of the quadrupole anisotropy. Interestingly, this effect survives even after the tensor mode decays when it re-enters the horizon, known as the fossil effect. As a result, the off-diagonal correlation function between different Fourier modes of the density fluctuations can be thought as a way to probe the large-scale GW and the mechanism of inflation behind themore » fossil effect. Models of single field slow roll inflation generically predict a very small quadrupole anisotropy in TSS while in models of multiple fields inflation this effect can be observable. Therefore this large scale quadrupole anisotropy can be thought as a spectroscopy for different inflationary models. In addition, in models of anisotropic inflation there exists quadrupole anisotropy in curvature perturbation power spectrum. Here we consider TSS in models of anisotropic inflation and show that the shape of quadrupole anisotropy is different than in single field models. In fact, in these models, quadrupole anisotropy is projected into the preferred direction and its amplitude is proportional to g{sub *} N{sub e} where N{sub e} is the number of e-folds and g{sub *} is the amplitude of quadrupole anisotropy in curvature perturbation power spectrum. We use this correlation function to estimate the large scale GW as well as the preferred direction and discuss the detectability of the signal in the galaxy surveys like Euclid and 21 cm surveys.« less

Large-scale patterns of benthic marine communities in the Brazilian Province.

PubMed

Aued, Anaide W; Smith, Franz; Quimbayo, Juan P; Cândido, Davi V; Longo, Guilherme O; Ferreira, Carlos E L; Witman, Jon D; Floeter, Sergio R; Segal, Bárbara

2018-01-01

As marine ecosystems are influenced by global and regional processes, standardized information on community structure has become crucial for assessing broad-scale responses to natural and anthropogenic disturbances. Extensive biogeographic provinces, such as the Brazilian Province in the southwest Atlantic, present numerous theoretical and methodological challenges for understanding community patterns on a macroecological scale. In particular, the Brazilian Province is composed of a complex system of heterogeneous reefs and a few offshore islands, with contrasting histories and geophysical-chemical environments. Despite the large extent of the Brazilian Province (almost 8,000 kilometers), most studies of shallow benthic communities are qualitative surveys and/or have been geographically restricted. We quantified community structure of shallow reef habitats from 0° to 27°S latitude using a standard photographic quadrat technique. Percent cover data indicated that benthic communities of Brazilian reefs were dominated by algal turfs and frondose macroalgae, with low percent cover of reef-building corals. Community composition differed significantly among localities, mostly because of their macroalgal abundance, despite reef type or geographic region, with no evident latitudinal pattern. Benthic diversity was lower in the tropics, contrary to the general latitudinal diversity gradient pattern. Richness peaked at mid-latitudes, between 20°S to 23°S, where it was ~3.5-fold higher than localities with the lowest richness. This study provides the first large-scale description of benthic communities along the southwestern Atlantic, providing a baseline for macroecological comparisons and evaluation of future impacts. Moreover, the new understanding of richness distribution along Brazilian reefs will contribute to conservation planning efforts, such as management strategies and the spatial prioritization for the creation of new marine protected areas.

Large-scale manufacture and characterization of a lentiviral vector produced for clinical ex vivo gene therapy application.

PubMed

Merten, Otto-Wilhelm; Charrier, Sabine; Laroudie, Nicolas; Fauchille, Sylvain; Dugué, Céline; Jenny, Christine; Audit, Muriel; Zanta-Boussif, Maria-Antonietta; Chautard, Hélène; Radrizzani, Marina; Vallanti, Giuliana; Naldini, Luigi; Noguiez-Hellin, Patricia; Galy, Anne

2011-03-01

From the perspective of a pilot clinical gene therapy trial for Wiskott-Aldrich syndrome (WAS), we implemented a process to produce a lentiviral vector under good manufacturing practices (GMP). The process is based on the transient transfection of 293T cells in Cell Factory stacks, scaled up to harvest 50 liters of viral stock per batch, followed by purification of the vesicular stomatitis virus glycoprotein-pseudotyped particles through several membrane-based and chromatographic steps. The process leads to a 200-fold volume concentration and an approximately 3-log reduction in protein and DNA contaminants. An average yield of 13% of infectious particles was obtained in six full-scale preparations. The final product contained low levels of contaminants such as simian virus 40 large T antigen or E1A sequences originating from producer cells. Titers as high as 2 × 10(9) infectious particles per milliliter were obtained, generating up to 6 × 10(11) infectious particles per batch. The purified WAS vector was biologically active, efficiently expressing the genetic insert in WAS protein-deficient B cell lines and transducing CD34(+) cells. The vector introduced 0.3-1 vector copy per cell on average in CD34(+) cells when used at the concentration of 10(8) infectious particles per milliliter, which is comparable to preclinical preparations. There was no evidence of cellular toxicity. These results show the implementation of large-scale GMP production, purification, and control of advanced HIV-1-derived lentiviral technology. Results obtained with the WAS vector provide the initial manufacturing and quality control benchmarking that should be helpful to further development and clinical applications.

Large-scale patterns of benthic marine communities in the Brazilian Province

PubMed Central

Smith, Franz; Quimbayo, Juan P.; Cândido, Davi V.; Longo, Guilherme O.; Ferreira, Carlos E. L.; Witman, Jon D.; Floeter, Sergio R.; Segal, Bárbara

2018-01-01

As marine ecosystems are influenced by global and regional processes, standardized information on community structure has become crucial for assessing broad-scale responses to natural and anthropogenic disturbances. Extensive biogeographic provinces, such as the Brazilian Province in the southwest Atlantic, present numerous theoretical and methodological challenges for understanding community patterns on a macroecological scale. In particular, the Brazilian Province is composed of a complex system of heterogeneous reefs and a few offshore islands, with contrasting histories and geophysical-chemical environments. Despite the large extent of the Brazilian Province (almost 8,000 kilometers), most studies of shallow benthic communities are qualitative surveys and/or have been geographically restricted. We quantified community structure of shallow reef habitats from 0° to 27°S latitude using a standard photographic quadrat technique. Percent cover data indicated that benthic communities of Brazilian reefs were dominated by algal turfs and frondose macroalgae, with low percent cover of reef-building corals. Community composition differed significantly among localities, mostly because of their macroalgal abundance, despite reef type or geographic region, with no evident latitudinal pattern. Benthic diversity was lower in the tropics, contrary to the general latitudinal diversity gradient pattern. Richness peaked at mid-latitudes, between 20°S to 23°S, where it was ~3.5-fold higher than localities with the lowest richness. This study provides the first large-scale description of benthic communities along the southwestern Atlantic, providing a baseline for macroecological comparisons and evaluation of future impacts. Moreover, the new understanding of richness distribution along Brazilian reefs will contribute to conservation planning efforts, such as management strategies and the spatial prioritization for the creation of new marine protected areas. PMID:29883496

Air-water oxygen exchange in a large whitewater river

USGS Publications Warehouse

Hall, Robert O.; Kennedy, Theodore A.; Rosi-Marshall, Emma J.

2012-01-01

Air-water gas exchange governs fluxes of gas into and out of aquatic ecosystems. Knowing this flux is necessary to calculate gas budgets (i.e., O2) to estimate whole-ecosystem metabolism and basin-scale carbon budgets. Empirical data on rates of gas exchange for streams, estuaries, and oceans are readily available. However, there are few data from large rivers and no data from whitewater rapids. We measured gas transfer velocity in the Colorado River, Grand Canyon, as decline in O2 saturation deficit, 7 times in a 28-km segment spanning 7 rapids. The O2 saturation deficit exists because of hypolimnetic discharge from Glen Canyon Dam, located 25 km upriver from Lees Ferry. Gas transfer velocity (k600) increased with slope of the immediate reach. k600 was -1 in flat reaches, while k600 for the steepest rapid ranged 3600-7700 cm h-1, an extremely high value of k600. Using the rate of gas exchange per unit length of water surface elevation (Kdrop, m-1), segment-integrated k600 varied between 74 and 101 cm h-1. Using Kdrop we scaled k600 to the remainder of the Colorado River in Grand Canyon. At the scale corresponding to the segment length where 80% of the O2 exchanged with the atmosphere (mean length = 26.1 km), k600 varied 4.5-fold between 56 and 272 cm h-1 with a mean of 113 cm h-1. Gas transfer velocity for the Colorado River was higher than those from other aquatic ecosystems because of large rapids. Our approach of scaling k600 based on Kdrop allows comparing gas transfer velocity across rivers with spatially heterogeneous morphology.

Deciphering hierarchical features in the energy landscape of adenylate kinase folding/unfolding

NASA Astrophysics Data System (ADS)

Taylor, J. Nicholas; Pirchi, Menahem; Haran, Gilad; Komatsuzaki, Tamiki

2018-03-01

Hierarchical features of the energy landscape of the folding/unfolding behavior of adenylate kinase, including its dependence on denaturant concentration, are elucidated in terms of single-molecule fluorescence resonance energy transfer (smFRET) measurements in which the proteins are encapsulated in a lipid vesicle. The core in constructing the energy landscape from single-molecule time-series across different denaturant concentrations is the application of rate-distortion theory (RDT), which naturally considers the effects of measurement noise and sampling error, in combination with change-point detection and the quantification of the FRET efficiency-dependent photobleaching behavior. Energy landscapes are constructed as a function of observation time scale, revealing multiple partially folded conformations at small time scales that are situated in a superbasin. As the time scale increases, these denatured states merge into a single basin, demonstrating the coarse-graining of the energy landscape as observation time increases. Because the photobleaching time scale is dependent on the conformational state of the protein, possible nonequilibrium features are discussed, and a statistical test for violation of the detailed balance condition is developed based on the state sequences arising from the RDT framework.

Genome sequencing in microfabricated high-density picolitre reactors.

PubMed

Margulies, Marcel; Egholm, Michael; Altman, William E; Attiya, Said; Bader, Joel S; Bemben, Lisa A; Berka, Jan; Braverman, Michael S; Chen, Yi-Ju; Chen, Zhoutao; Dewell, Scott B; Du, Lei; Fierro, Joseph M; Gomes, Xavier V; Godwin, Brian C; He, Wen; Helgesen, Scott; Ho, Chun Heen; Ho, Chun He; Irzyk, Gerard P; Jando, Szilveszter C; Alenquer, Maria L I; Jarvie, Thomas P; Jirage, Kshama B; Kim, Jong-Bum; Knight, James R; Lanza, Janna R; Leamon, John H; Lefkowitz, Steven M; Lei, Ming; Li, Jing; Lohman, Kenton L; Lu, Hong; Makhijani, Vinod B; McDade, Keith E; McKenna, Michael P; Myers, Eugene W; Nickerson, Elizabeth; Nobile, John R; Plant, Ramona; Puc, Bernard P; Ronan, Michael T; Roth, George T; Sarkis, Gary J; Simons, Jan Fredrik; Simpson, John W; Srinivasan, Maithreyan; Tartaro, Karrie R; Tomasz, Alexander; Vogt, Kari A; Volkmer, Greg A; Wang, Shally H; Wang, Yong; Weiner, Michael P; Yu, Pengguang; Begley, Richard F; Rothberg, Jonathan M

2005-09-15

The proliferation of large-scale DNA-sequencing projects in recent years has driven a search for alternative methods to reduce time and cost. Here we describe a scalable, highly parallel sequencing system with raw throughput significantly greater than that of state-of-the-art capillary electrophoresis instruments. The apparatus uses a novel fibre-optic slide of individual wells and is able to sequence 25 million bases, at 99% or better accuracy, in one four-hour run. To achieve an approximately 100-fold increase in throughput over current Sanger sequencing technology, we have developed an emulsion method for DNA amplification and an instrument for sequencing by synthesis using a pyrosequencing protocol optimized for solid support and picolitre-scale volumes. Here we show the utility, throughput, accuracy and robustness of this system by shotgun sequencing and de novo assembly of the Mycoplasma genitalium genome with 96% coverage at 99.96% accuracy in one run of the machine.

Structural correction of paleomagnetic vectors dispersed about two fold axes and application to the Duke Island (Alaska) ultramafic complex

NASA Astrophysics Data System (ADS)

Bogue, Scott W.; Grommé, C. Sherman

2004-11-01

A new analysis of paleomagnetic data from the mid-Cretaceous (˜110 Ma) ultramafic complex at Duke Island (southeast Alaska) supports large poleward transport of the Insular superterrane relative to North America consistent with the Baja British Columbia hypothesis. Previous paleomagnetic work has shown that the characteristic remanence of the ultramafic complex predates kilometer-scale deformation of the very well developed cumulate layering but that the layering was not horizontal everywhere before the folding. It is possible, however, to estimate paleohorizontal for the Duke Island ultramafic complex because the postremanence deformation of the intrusion occurred about two well-defined and spatially separate fold axes. In such a case the tectonically rotated paleomagnetic directions should be distributed along small circles centered on each of the two fold axes. The ancient field direction will lie on both small circles and therefore will be identifiable as one of their two intersection points. Interpreted this way, the tectonically rotated remanence of the Duke Island ultramafic complex defines a mid-Cretaceous (i.e., ancient) field direction that is within 2° of the paleomagnetic direction found by assuming the cumulate layering was initially horizontal (despite the paleomagnetic evidence to the contrary) and performing the standard structure correction. The inferred mid-Cretaceous paleolatitude of Duke Island is 21.2° (2350 km) anomalous with respect to cratonic North America. This result is concordant with southerly paleolatitudes determined by many other workers from bedded rocks of terranes farther inboard in the Insular and Intermontane superterranes.

Complex vibratory patterns in an elephant larynx.

PubMed

Herbst, Christian T; Svec, Jan G; Lohscheller, Jörg; Frey, Roland; Gumpenberger, Michaela; Stoeger, Angela S; Fitch, W Tecumseh

2013-11-01

Elephants' low-frequency vocalizations are produced by flow-induced self-sustaining oscillations of laryngeal tissue. To date, little is known in detail about the vibratory phenomena in the elephant larynx. Here, we provide a first descriptive report of the complex oscillatory features found in the excised larynx of a 25 year old female African elephant (Loxodonta africana), the largest animal sound generator ever studied experimentally. Sound production was documented with high-speed video, acoustic measurements, air flow and sound pressure level recordings. The anatomy of the larynx was studied with computed tomography (CT) and dissections. Elephant CT vocal anatomy data were further compared with the anatomy of an adult human male. We observed numerous unusual phenomena, not typically reported in human vocal fold vibrations. Phase delays along both the inferior-superior and anterior-posterior (A-P) dimension were commonly observed, as well as transverse travelling wave patterns along the A-P dimension, previously not documented in the literature. Acoustic energy was mainly created during the instant of glottal opening. The vestibular folds, when adducted, participated in tissue vibration, effectively increasing the generated sound pressure level by 12 dB. The complexity of the observed phenomena is partly attributed to the distinct laryngeal anatomy of the elephant larynx, which is not simply a large-scale version of its human counterpart. Travelling waves may be facilitated by low fundamental frequencies and increased vocal fold tension. A travelling wave model is proposed, to account for three types of phenomena: A-P travelling waves, 'conventional' standing wave patterns, and irregular vocal fold vibration.

Diverse and abundant antibiotic resistance genes in Chinese swine farms

PubMed Central

Zhu, Yong-Guan; Johnson, Timothy A.; Su, Jian-Qiang; Qiao, Min; Guo, Guang-Xia; Stedtfeld, Robert D.; Hashsham, Syed A.; Tiedje, James M.

2013-01-01

Antibiotic resistance genes (ARGs) are emerging contaminants posing a potential worldwide human health risk. Intensive animal husbandry is believed to be a major contributor to the increased environmental burden of ARGs. Despite the volume of antibiotics used in China, little information is available regarding the corresponding ARGs associated with animal farms. We assessed type and concentrations of ARGs at three stages of manure processing to land disposal at three large-scale (10,000 animals per year) commercial swine farms in China. In-feed or therapeutic antibiotics used on these farms include all major classes of antibiotics except vancomycins. High-capacity quantitative PCR arrays detected 149 unique resistance genes among all of the farm samples, the top 63 ARGs being enriched 192-fold (median) up to 28,000-fold (maximum) compared with their respective antibiotic-free manure or soil controls. Antibiotics and heavy metals used as feed supplements were elevated in the manures, suggesting the potential for coselection of resistance traits. The potential for horizontal transfer of ARGs because of transposon-specific ARGs is implicated by the enrichment of transposases—the top six alleles being enriched 189-fold (median) up to 90,000-fold in manure—as well as the high correlation (r2 = 0.96) between ARG and transposase abundance. In addition, abundance of ARGs correlated directly with antibiotic and metal concentrations, indicating their importance in selection of resistance genes. Diverse, abundant, and potentially mobile ARGs in farm samples suggest that unmonitored use of antibiotics and metals is causing the emergence and release of ARGs to the environment. PMID:23401528

Domain structure of the ribozyme from eubacterial ribonuclease P.

PubMed Central

Loria, A; Pan, T

1996-01-01

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

Thermoreversible Folding as a Route to the Unique Shape-Memory Character in Ductile Polymer Networks.

PubMed

McBride, Matthew K; Podgorski, Maciej; Chatani, Shunsuke; Worrell, Brady T; Bowman, Christopher N

2018-06-21

Ductile, cross-linked films were folded as a means to program temporary shapes without the need for complex heating cycles or specialized equipment. Certain cross-linked polymer networks, formed here with the thiol-isocyanate reaction, possessed the ability to be pseudoplastically deformed below the glass transition, and the original shape was recovered during heating through the glass transition. To circumvent the large forces required to plastically deform a glassy polymer network, we have utilized folding, which localizes the deformation in small creases, and achieved large dimensional changes with simple programming procedures. In addition to dimension changes, three-dimensional objects such as swans and airplanes were developed to demonstrate applying origami principles to shape memory. We explored the fundamental mechanical properties that are required to fold polymer sheets and observed that a yield point that does not correspond to catastrophic failure is required. Unfolding occurred during heating through the glass transition, indicating the vitrification of the network that maintained the temporary, folded shape. Folding was demonstrated as a powerful tool to simply and effectively program ductile shape-memory polymers without the need for thermal cycling.

Globalization of the cashmere market and the decline of large mammals in central Asia.

PubMed

Berger, Joel; Buuveibaatar, Bayarbaatar; Mishra, Charudutt

2013-08-01

As drivers of terrestrial ecosystems, humans have replaced large carnivores in most areas, and human influence not only exerts striking ecological pressures on biodiversity at local scales but also has indirect effects in distant corners of the world. We suggest that the multibillion dollar cashmere industry creates economic motivations that link western fashion preferences for cashmere to land use in Central Asia. This penchant for stylish clothing, in turn, encourages herders to increase livestock production which affects persistence of over 6 endangered large mammals in these remote, arid ecosystems. We hypothesized that global trade in cashmere has strong negative effects on native large mammals of deserts and grassland where cashmere-producing goats are raised. We used time series data, ecological snapshots of the biomass of native and domestic ungulates, and ecologically and behaviorally based fieldwork to test our hypothesis. In Mongolia increases in domestic goat production were associated with a 3-fold increase in local profits for herders coexisting with endangered saiga (Saiga tatarica).That increasing domestic grazing pressure carries fitness consequences was inferred on the basis of an approximately 4-fold difference in juvenile recruitment among blue sheep (Pseudois nayaur)in trans-Himalayan India. Across 7 study areas in Mongolia, India, and China's Tibetan Plateau, native ungulate biomass is now <5% that of domestic species. Such trends suggest ecosystem degradation and decreased capacity for the persistence of native species, including at least 8 Asian endemic species: saiga, chiru (Pantholops hodgsoni), Bactrian camel (Camelus bactrianus), snow leopard(Panthera uncia), khulan(Equus hemionus), kiang (E. kiang), takhi (E. przewalski), and wild yak (Bos mutus). Our results suggest striking yet indirect and unintended actions that link trophic-level effects to markets induced by the trade for cashmere. © 2013 Society for Conservation Biology.

Fold pattern formation in 3D

NASA Astrophysics Data System (ADS)

Schmid, Daniel W.; Dabrowski, Marcin; Krotkiewski, Marcin

2010-05-01

The vast majority of studies concerned with folding focus on 2D and assume that the resulting fold structures are cylindrically extended in the out of place direction. This simplification is often justified as fold aspect ratios, length/width, are quite large. However, folds always exhibit finite aspect ratios and it is unclear what controls this (cf. Fletcher 1995). Surprisingly little is known about the fold pattern formation in 3D for different in-plane loading conditions. Even more complicated is the pattern formation when several folding events are superposed. Let us take the example of a plane strain pure shear superposed by the same kind of deformation but rotated by 90 degrees. The text book prediction for this event is the formation of an egg carton structure; relevant analogue models either agree and produce type 1 interference patterns or contradict and produce type 2. In order to map out 3D fold pattern formation we have performed a systematic parameter space investigation using BILAMIN, our efficient unstructured mesh finite element Stokes solver. BILAMIN is capable of solving problems with more than half a billion unknowns. This allows us to study fold patterns that emerge in randomly (red noise) perturbed layers. We classify the resulting structures with differential geometry tools. Our results show that there is a relationship between fold aspect ratio and in-plane loading conditions. We propose that this finding can be used to determine the complete parameter set potentially contained in the geometry of three dimensional folds: mechanical properties of natural rocks, maximum strain, and relative strength of the in-plane far-field load components. Furthermore, we show how folds in 3D amplify and that there is a second deformation mode, besides continuous amplification, where compression leads to a lateral rearrangement of blocks of folds. Finally, we demonstrate that the textbook prediction of egg carton shaped dome and basin structures resulting from folding instabilities in constriction is largely oversimplified. The fold patterns resulting in this setting are curved, elongated folds with random orientation. Reference Fletcher, R. C. 1995. 3-Dimensional Folding and Necking of a Power-Law Layer - Are Folds Cylindrical, and, If So, Do We Understand Why. Tectonophysics 147(1-4), 65-83.

Machinery of protein folding and unfolding.

PubMed

Zhang, Xiaodong; Beuron, Fabienne; Freemont, Paul S

2002-04-01

During the past two years, a large amount of biochemical, biophysical and low- to high-resolution structural data have provided mechanistic insights into the machinery of protein folding and unfolding. It has emerged that dual functionality in terms of folding and unfolding might exist for some systems. The majority of folding/unfolding machines adopt oligomeric ring structures in a cooperative fashion and utilise the conformational changes induced by ATP binding/hydrolysis for their specific functions.

Breccia dikes from the Beaverhead Impact structure, southwest Montana

NASA Technical Reports Server (NTRS)

Fiske, P. S.; Hougen, S. B.; Hargraves, R. B.

1992-01-01

While shatter cones are generally accepted as indicators of meteorite impact, older petrologic features are not widely recognized in the geologic community. Breccia dikes are one such feature. They are found in many large impact structures occurring over an area at least as extensively as shatter cones. Breccia dikes will survive moderate degrees of metamorphism and tectonism, unlike many other microscopic features (shocked quartz grains, high-pressure polymorphs, etc.) and even large-scale features such as annular or bowl-shaped topographic features. Thus, they are important diagnostic criteria, especially for large, poorly preserved impact structures. The Beaverhead Impact structure is a recently discovered, deeply eroded impact structure in southwestern Montana. The remains of the structure are delineated by the occurrence of shatter cones, found in an area greater than 200 sq km, occurring within the Cabin thrust plate, part of the Cretaceous Sevier fold and thrust system. The distribution of shatter cones is further truncated by Tertiary normal faults. The present remains represent an allochthonous fragment of a larger structure.

Droplet-based microfluidic flow injection system with large-scale concentration gradient by a single nanoliter-scale injection for enzyme inhibition assay.

PubMed

Cai, Long-Fei; Zhu, Ying; Du, Guan-Sheng; Fang, Qun

2012-01-03

We described a microfluidic chip-based system capable of generating droplet array with a large scale concentration gradient by coupling flow injection gradient technique with droplet-based microfluidics. Multiple modules including sample injection, sample dispersion, gradient generation, droplet formation, mixing of sample and reagents, and online reaction within the droplets were integrated into the microchip. In the system, nanoliter-scale sample solution was automatically injected into the chip under valveless flow injection analysis mode. The sample zone was first dispersed in the microchannel to form a concentration gradient along the axial direction of the microchannel and then segmented into a linear array of droplets by immiscible oil phase. With the segmentation and protection of the oil phase, the concentration gradient profile of the sample was preserved in the droplet array with high fidelity. With a single injection of 16 nL of sample solution, an array of droplets with concentration gradient spanning 3-4 orders of magnitude could be generated. The present system was applied in the enzyme inhibition assay of β-galactosidase to preliminarily demonstrate its potential in high throughput drug screening. With a single injection of 16 nL of inhibitor solution, more than 240 in-droplet enzyme inhibition reactions with different inhibitor concentrations could be performed with an analysis time of 2.5 min. Compared with multiwell plate-based screening systems, the inhibitor consumption was reduced 1000-fold. © 2011 American Chemical Society

A recombinant CYP11B1 dependent Escherichia coli biocatalyst for selective cortisol production and optimization towards a preparative scale.

PubMed

Schiffer, Lina; Anderko, Simone; Hobler, Anna; Hannemann, Frank; Kagawa, Norio; Bernhardt, Rita

2015-02-25

Human mitochondrial CYP11B1 catalyzes a one-step regio- and stereoselective 11β-hydroxylation of 11-deoxycortisol yielding cortisol which constitutes not only the major human stress hormone but also represents a commercially relevant therapeutic drug due to its anti-inflammatory and immunosuppressive properties. Moreover, it is an important intermediate in the industrial production of synthetic pharmaceutical glucocorticoids. CYP11B1 thus offers a great potential for biotechnological application in large-scale synthesis of cortisol. Because of its nature as external monooxygenase, CYP11B1-dependent steroid hydroxylation requires reducing equivalents which are provided from NADPH via a redox chain, consisting of adrenodoxin reductase (AdR) and adrenodoxin (Adx). We established an Escherichia coli based whole-cell system for selective cortisol production from 11-deoxycortisol by recombinant co-expression of the demanded 3 proteins. For the subsequent optimization of the whole-cell activity 3 different approaches were pursued: Firstly, CYP11B1 expression was enhanced 3.3-fold to 257 nmol∗L(-1) by site-directed mutagenesis of position 23 from glycine to arginine, which was accompanied by a 2.6-fold increase in cortisol yield. Secondly, the electron transfer chain was engineered in a quantitative manner by introducing additional copies of the Adx cDNA in order to enhance Adx expression on transcriptional level. In the presence of 2 and 3 copies the initial linear conversion rate was greatly accelerated and the final product concentration was improved 1.4-fold. Thirdly, we developed a screening system for directed evolution of CYP11B1 towards higher hydroxylation activity. A culture down-scale to microtiter plates was performed and a robot-assisted, fluorescence-based conversion assay was applied for the selection of more efficient mutants from a random library. Under optimized conditions a maximum productivity of 0.84 g cortisol∗L(-1)∗d(-1) was achieved, which clearly shows the potential of the developed system for application in the pharmaceutical industry.

An all-atom structure-based potential for proteins: bridging minimal models with all-atom empirical forcefields.

PubMed

Whitford, Paul C; Noel, Jeffrey K; Gosavi, Shachi; Schug, Alexander; Sanbonmatsu, Kevin Y; Onuchic, José N

2009-05-01

Protein dynamics take place on many time and length scales. Coarse-grained structure-based (Go) models utilize the funneled energy landscape theory of protein folding to provide an understanding of both long time and long length scale dynamics. All-atom empirical forcefields with explicit solvent can elucidate our understanding of short time dynamics with high energetic and structural resolution. Thus, structure-based models with atomic details included can be used to bridge our understanding between these two approaches. We report on the robustness of folding mechanisms in one such all-atom model. Results for the B domain of Protein A, the SH3 domain of C-Src Kinase, and Chymotrypsin Inhibitor 2 are reported. The interplay between side chain packing and backbone folding is explored. We also compare this model to a C(alpha) structure-based model and an all-atom empirical forcefield. Key findings include: (1) backbone collapse is accompanied by partial side chain packing in a cooperative transition and residual side chain packing occurs gradually with decreasing temperature, (2) folding mechanisms are robust to variations of the energetic parameters, (3) protein folding free-energy barriers can be manipulated through parametric modifications, (4) the global folding mechanisms in a C(alpha) model and the all-atom model agree, although differences can be attributed to energetic heterogeneity in the all-atom model, and (5) proline residues have significant effects on folding mechanisms, independent of isomerization effects. Because this structure-based model has atomic resolution, this work lays the foundation for future studies to probe the contributions of specific energetic factors on protein folding and function.

An All-atom Structure-Based Potential for Proteins: Bridging Minimal Models with All-atom Empirical Forcefields

PubMed Central

Whitford, Paul C.; Noel, Jeffrey K.; Gosavi, Shachi; Schug, Alexander; Sanbonmatsu, Kevin Y.; Onuchic, José N.

2012-01-01

Protein dynamics take place on many time and length scales. Coarse-grained structure-based (Gō) models utilize the funneled energy landscape theory of protein folding to provide an understanding of both long time and long length scale dynamics. All-atom empirical forcefields with explicit solvent can elucidate our understanding of short time dynamics with high energetic and structural resolution. Thus, structure-based models with atomic details included can be used to bridge our understanding between these two approaches. We report on the robustness of folding mechanisms in one such all-atom model. Results for the B domain of Protein A, the SH3 domain of C-Src Kinase and Chymotrypsin Inhibitor 2 are reported. The interplay between side chain packing and backbone folding is explored. We also compare this model to a Cα structure-based model and an all-atom empirical forcefield. Key findings include 1) backbone collapse is accompanied by partial side chain packing in a cooperative transition and residual side chain packing occurs gradually with decreasing temperature 2) folding mechanisms are robust to variations of the energetic parameters 3) protein folding free energy barriers can be manipulated through parametric modifications 4) the global folding mechanisms in a Cα model and the all-atom model agree, although differences can be attributed to energetic heterogeneity in the all-atom model 5) proline residues have significant effects on folding mechanisms, independent of isomerization effects. Since this structure-based model has atomic resolution, this work lays the foundation for future studies to probe the contributions of specific energetic factors on protein folding and function. PMID:18837035

Multiple stepwise refolding of immunoglobulin domain I27 upon force quench depends on initial conditions

PubMed Central

Li, Mai Suan; Hu, Chin-Kun; Klimov, Dmitri K.; Thirumalai, D.

2006-01-01

Mechanical folding trajectories for polyproteins starting from initially stretched conformations generated by single-molecule atomic force microscopy experiments [Fernandez, J. M. & Li, H. (2004) Science 303, 1674–1678] show that refolding, monitored by the end-to-end distance, occurs in distinct multiple stages. To clarify the molecular nature of folding starting from stretched conformations, we have probed the folding dynamics, upon force quench, for the single I27 domain from the muscle protein titin by using a Cα-Go model. Upon temperature quench, collapse and folding of I27 are synchronous. In contrast, refolding from stretched initial structures not only increases the folding and collapse time scales but also decouples the two kinetic processes. The increase in the folding times is associated primarily with the stretched state to compact random coil transition. Surprisingly, force quench does not alter the nature of the refolding kinetics, but merely increases the height of the free-energy folding barrier. Force quench refolding times scale as \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} \\begin{equation*}{\\tau}_{F}\\approx {\\tau}_{F}^{0}{\\mathrm{exp}}(f_{q}{\\Delta}x_{f}/k_{{\\mathrm{B}}}T)\\end{equation*}\\end{document}, where Δxf ≈ 0.6 nm is the location of the average transition state along the reaction coordinate given by end-to-end distance. We predict that τF and the folding mechanism can be dramatically altered by the initial and/or final values of force. The implications of our results for design and analysis of experiments are discussed. PMID:16373511

The scaling features of the 3D organization of chromosomes are highlighted by a transformation à la Kadanoff of Hi-C data

NASA Astrophysics Data System (ADS)

Chiariello, Andrea M.; Bianco, Simona; Annunziatella, Carlo; Esposito, Andrea; Nicodemi, Mario

2017-11-01

Technologies such as Hi-C and GAM have revealed that chromosomes are not randomly folded into the nucleus of cells, but are composed by a sequence of contact domains (TADs), each typically 0.5 Mb long. However, the larger scale organization of the genome remains still not well understood. To investigate the scaling behaviour of chromosome folding, here we apply an approach à la Kadanoff, inspired by the Renormalization Group theory, to Hi-C interaction data, across different cell types and chromosomes. We find that the genome is characterized by complex scaling features, where the average size of contact domains exhibits a power-law behaviour with the rescaling level. That is compatible with the existence of contact domains extending across length scales up to chromosomal sizes. The scaling exponent is statistically indistinguishable among the different murine cell types analysed. These results point toward a scenario of a universal higher-order spatial architecture of the genome, which could reflect fundamental, organizational principles.

Sinuous Flow in Cutting of Metals

NASA Astrophysics Data System (ADS)

Yeung, Ho; Viswanathan, Koushik; Udupa, Anirudh; Mahato, Anirban; Chandrasekar, Srinivasan

2017-11-01

Using in situ high-speed imaging, we unveil details of a highly unsteady plastic flow mode in the cutting of annealed and highly strain-hardening metals. This mesoscopic flow mode, termed sinuous flow, is characterized by repeated material folding, large rotation, and energy dissipation. Sinuous flow effects a very large shape transformation, with local strains of ten or more, and results in a characteristic mushroomlike surface morphology that is quite distinct from the well-known morphologies of metal-cutting chips. Importantly, the attributes of this unsteady flow are also fundamentally different from other well-established unsteady plastic flows in large-strain deformation, like adiabatic shear bands. The nucleation and development of sinuous flow, its dependence on material properties, and its manifestation across material systems are demonstrated. Plastic buckling and grain-scale heterogeneity are found to play key roles in triggering this flow at surfaces. Implications for modeling and understanding flow stability in large-strain plastic deformation, surface quality, and preparation of near-strain-free surfaces by cutting are discussed. The results point to the inadequacy of the widely used shear-zone models, even for ductile metals.

Observations of Convective and Dynamical Instabilities in Tropopause Folds and their Contribution to Stratosphere-Troposphere Exchange

NASA Technical Reports Server (NTRS)

Cho, John Y. N.; Newell, Reginald E.; Bui, T. Paul; Browell, Edward V.; Fenn, Martha A.; Gary, Bruce L.; Mahoney, Michael J.; Gregory, Gerald L.; Sachse, Glen W.; Vay, Stephanie A.

1999-01-01

With aircraft-mounted in-situ and remote sensing instruments for dynamical, thermal. and chemical measurements, we studied two cases of tropopause folding. In both folds we found Kelvin-Helmholtz billows with horizontal wavelength of about 900 m and thickness of about 120 m. In one case the instability was effectively mixing the bottomside of the fold, leading to the transfer of stratospheric air into the troposphere. Also we discovered in both cases small-scale secondary ozone maxima shortly after the aircraft ascended past the topside of the fold that corresponded to regions of convective instability. We interpreted this phenomenon as convectively breaking gravity waves. Therefore, we posit that convectively breaking gravity waves acting on tropopause folds must be added to the list of important irreversible mixing mechanisms leading to stratosphere-troposphere exchange.

Mapping the energy landscape for second-stage folding of a single membrane protein

PubMed Central

Min, Duyoung; Jefferson, Robert E; Bowie, James U; Yoon, Tae-Young

2016-01-01

Membrane proteins are designed to fold and function in a lipid membrane, yet folding experiments within a native membrane environment are challenging to design. Here we show that single-molecule forced unfolding experiments can be adapted to study helical membrane protein folding under native-like bicelle conditions. Applying force using magnetic tweezers, we find that a transmembrane helix protein, Escherichia coli rhomboid protease GlpG, unfolds in a highly cooperative manner, largely unraveling as one physical unit in response to mechanical tension above 25 pN. Considerable hysteresis is observed, with refolding occurring only at forces below 5 pN. Characterizing the energy landscape reveals only modest thermodynamic stability (ΔG = 6.5 kBT) but a large unfolding barrier (21.3 kBT) that can maintain the protein in a folded state for long periods of time (t1/2 ~3.5 h). The observed energy landscape may have evolved to limit the existence of troublesome partially unfolded states and impart rigidity to the structure. PMID:26479439

Subaqueous Sediment Remobilization and Development of Syndepositional Deformational Structures on Mars: A Kinematic Approach from the Noachian Terby Crater

NASA Astrophysics Data System (ADS)

Sarkar, R.; Das, P.; Basu Sarbadhikari, A.

2017-12-01

A 2 km thick layered sequence within the Noachian Terby crater ( 174 km diameter, 28.0°S - 74.0°E), located at the Northern rim of Hellas basin, has been re-classified here into three major categories, i.e. mega-slump, debris flows, and turbidites based on sedimentation process. A wide spectrum of deformation structures, such as large scale isoclinal moderately inclined fold, pinch and swells, disharmonic folds, sediment loading structure, normal faults and thrust duplexes, suggest that amplitude of the syndepositional deformation spanned from hydroplastic to brittle domains. These structures provide ample evidences of sediment remobilization in Terby. The dominance of such mass-flow deposits in different stratigraphic horizons indicates that the basin was reactivated in frequent intervals during the filling process. However, an undeformed thinning-up sequence of beds, well exhibited at the basinal-lows, identified as ponded/confined turbidites, indicates that the basin experienced a stable bathymetric condition at the up-dip areas of the mega-slumps. An overall enrichment of phyllosilicates and scarcity of large boulders at the basin margins indicates that the provenance materials were deposited under stable and low-energy condition before being transported and re-deposited within the crater during the Terby impact. We presume that the inter-crater layered terrain of Hellas acted as a provenance of Terby's mass-transport deposits.

Activated carbon enhanced anaerobic digestion of food waste - Laboratory-scale and Pilot-scale operation.

PubMed

Zhang, Le; Zhang, Jingxin; Loh, Kai-Chee

2018-05-01

Effects of activated carbon (AC) supplementation on anaerobic digestion (AD) of food waste were elucidated in lab- and pilot-scales. Lab-scale AD was performed in 1 L and 8 L digesters, while pilot-scale AD was conducted in a 1000 L digester. Based on the optimal dose of 15 g AC per working volume derived from the 1 L digester, for the same AC dosage in the 8 L digester, an improved operation stability coupled with a higher methane yield was achieved even when digesters without AC supplementation failed after 59 days due to accumulation of substantial organic intermediates. At the same time, color removal from the liquid phase of the digestate was dramatically enhanced and the particle size of the digestate solids was increased by 53% through AC supplementation after running for 59 days. Pyrosequencing of 16S rRNA gene showed the abundance of predominant phyla Firmicutes, Elusimicrobia and Proteobacteria selectively enhanced by 1.7-fold, 2.9-fold and 2.1-fold, respectively. Pilot-scale digester without AC gave an average methane yield of 0.466 L⋅(gVS) -1 ⋅d -1 at a composition of 53-61% v/v methane. With AC augmentation, an increase of 41% in methane yield was achieved in the 1000 L digester under optimal organic loading rate (1.6 g VS FW ·L -1 ·d -1 ). Copyright © 2018 Elsevier Ltd. All rights reserved.

A weighted sampling algorithm for the design of RNA sequences with targeted secondary structure and nucleotide distribution.

PubMed

Reinharz, Vladimir; Ponty, Yann; Waldispühl, Jérôme

2013-07-01

The design of RNA sequences folding into predefined secondary structures is a milestone for many synthetic biology and gene therapy studies. Most of the current software uses similar local search strategies (i.e. a random seed is progressively adapted to acquire the desired folding properties) and more importantly do not allow the user to control explicitly the nucleotide distribution such as the GC-content in their sequences. However, the latter is an important criterion for large-scale applications as it could presumably be used to design sequences with better transcription rates and/or structural plasticity. In this article, we introduce IncaRNAtion, a novel algorithm to design RNA sequences folding into target secondary structures with a predefined nucleotide distribution. IncaRNAtion uses a global sampling approach and weighted sampling techniques. We show that our approach is fast (i.e. running time comparable or better than local search methods), seedless (we remove the bias of the seed in local search heuristics) and successfully generates high-quality sequences (i.e. thermodynamically stable) for any GC-content. To complete this study, we develop a hybrid method combining our global sampling approach with local search strategies. Remarkably, our glocal methodology overcomes both local and global approaches for sampling sequences with a specific GC-content and target structure. IncaRNAtion is available at csb.cs.mcgill.ca/incarnation/. Supplementary data are available at Bioinformatics online.

Robust optimization of the billet for isothermal local loading transitional region of a Ti-alloy rib-web component based on dual-response surface method

NASA Astrophysics Data System (ADS)

Wei, Ke; Fan, Xiaoguang; Zhan, Mei; Meng, Miao

2018-03-01

Billet optimization can greatly improve the forming quality of the transitional region in the isothermal local loading forming (ILLF) of large-scale Ti-alloy ribweb components. However, the final quality of the transitional region may be deteriorated by uncontrollable factors, such as the manufacturing tolerance of the preforming billet, fluctuation of the stroke length, and friction factor. Thus, a dual-response surface method (RSM)-based robust optimization of the billet was proposed to address the uncontrollable factors in transitional region of the ILLF. Given that the die underfilling and folding defect are two key factors that influence the forming quality of the transitional region, minimizing the mean and standard deviation of the die underfilling rate and avoiding folding defect were defined as the objective function and constraint condition in robust optimization. Then, the cross array design was constructed, a dual-RSM model was established for the mean and standard deviation of the die underfilling rate by considering the size parameters of the billet and uncontrollable factors. Subsequently, an optimum solution was derived to achieve the robust optimization of the billet. A case study on robust optimization was conducted. Good results were attained for improving the die filling and avoiding folding defect, suggesting that the robust optimization of the billet in the transitional region of the ILLF was efficient and reliable.

Purification and substrate specificity of Staphylococcus hyicus lipase.

PubMed

van Oort, M G; Deveer, A M; Dijkman, R; Tjeenk, M L; Verheij, H M; de Haas, G H; Wenzig, E; Götz, F

1989-11-28

The Staphylococcus hyicus lipase gene has been cloned and expressed in Staphylococcus carnosus. From the latter organism the enzyme was secreted into the medium as a protein with an apparent molecular mass of 86 kDa. This protein was purified, and the amino-terminal sequence showed that the primary gene product was indeed cleaved at the proposed signal peptide cleavage site. The protein was purified from large-scale preparations after tryptic digestion. This limited proteolysis reduced the molecular mass to 46 kDa and increased the specific activity about 3-fold. Although the enzyme had a low specific activity in the absence of divalent cations, the activity increased about 40-fold in the presence of Sr2+ or Ca2+ ions. The purified lipase has a broad substrate specificity. The acyl chains were removed from the primary and secondary positions of natural neutral glycerides and from a variety of synthetic glyceride analogues. Thus triglycerides were fully hydrolyzed to free fatty acid and glycerol. The enzyme hydrolyzed naturally occurring phosphatidylcholines, their synthetic short-chain analogues, and lysophospholipids to free fatty acids and water-soluble products. The enzyme had a 2-fold higher activity on micelles of short-chain D-lecithins than on micelles composed of the L-isomers. Thus the enzyme from S. hyicus has lipase activity and also high phospholipase A and lysophospholipase activity.

Statistical theory for protein combinatorial libraries. Packing interactions, backbone flexibility, and the sequence variability of a main-chain structure.

PubMed

Kono, H; Saven, J G

2001-02-23

Combinatorial experiments provide new ways to probe the determinants of protein folding and to identify novel folding amino acid sequences. These types of experiments, however, are complicated both by enormous conformational complexity and by large numbers of possible sequences. Therefore, a quantitative computational theory would be helpful in designing and interpreting these types of experiment. Here, we present and apply a statistically based, computational approach for identifying the properties of sequences compatible with a given main-chain structure. Protein side-chain conformations are included in an atom-based fashion. Calculations are performed for a variety of similar backbone structures to identify sequence properties that are robust with respect to minor changes in main-chain structure. Rather than specific sequences, the method yields the likelihood of each of the amino acids at preselected positions in a given protein structure. The theory may be used to quantify the characteristics of sequence space for a chosen structure without explicitly tabulating sequences. To account for hydrophobic effects, we introduce an environmental energy that it is consistent with other simple hydrophobicity scales and show that it is effective for side-chain modeling. We apply the method to calculate the identity probabilities of selected positions of the immunoglobulin light chain-binding domain of protein L, for which many variant folding sequences are available. The calculations compare favorably with the experimentally observed identity probabilities.

Morphological and enzymatic response of the thermotolerant fungus Fomes sp. EUM1 in solid state fermentation under thermal stress.

PubMed

Ordaz-Hernández, Armando; Ortega-Sánchez, Eric; Montesinos-Matías, Roberto; Hernández-Martínez, Ricardo; Torres-Martínez, Daniel; Loera, Octavio

2016-08-01

Thermotolerance of the fungus Fomes sp. EUM1 was evaluated in solid state fermentation (SSF). This thermotolerant strain improved both hyphal invasiveness (38%) and length (17%) in adverse thermal conditions exceeding 30°C and to a maximum of 40°C. In contrast, hyphal branching decreased by 46% at 45°C. The production of cellulases over corn stover increased 1.6-fold in 30°C culture conditions, xylanases increased 2.8-fold at 40°C, while laccase production improved 2.7-fold at 35°C. Maximum production of lignocellulolytic enzymes was obtained at elevated temperatures in shorter fermentation times (8-6 days), although the proteases appeared as a thermal stress response associated with a drop in lignocellulolytic activities. Novel and multiple isoenzymes of xylanase (four bands) and cellulase (six bands) were secreted in the range of 20-150 kDa during growth in adverse temperature conditions. However, only a single laccase isoenzyme (46 kDa) was detected. This is the first report describing the advantages of a thermotolerant white-rot fungus in SSF. These results have important implications for large-scale SSF, where effects of metabolic heat are detrimental to growth and enzyme production, which are severely affected by the formation of high temperature gradients. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Adapted to Roar: Functional Morphology of Tiger and Lion Vocal Folds

PubMed Central

Klemuk, Sarah A.; Riede, Tobias; Walsh, Edward J.; Titze, Ingo R.

2011-01-01

Vocal production requires active control of the respiratory system, larynx and vocal tract. Vocal sounds in mammals are produced by flow-induced vocal fold oscillation, which requires vocal fold tissue that can sustain the mechanical stress during phonation. Our understanding of the relationship between morphology and vocal function of vocal folds is very limited. Here we tested the hypothesis that vocal fold morphology and viscoelastic properties allow a prediction of fundamental frequency range of sounds that can be produced, and minimal lung pressure necessary to initiate phonation. We tested the hypothesis in lions and tigers who are well-known for producing low frequency and very loud roaring sounds that expose vocal folds to large stresses. In histological sections, we found that the Panthera vocal fold lamina propria consists of a lateral region with adipocytes embedded in a network of collagen and elastin fibers and hyaluronan. There is also a medial region that contains only fibrous proteins and hyaluronan but no fat cells. Young's moduli range between 10 and 2000 kPa for strains up to 60%. Shear moduli ranged between 0.1 and 2 kPa and differed between layers. Biomechanical and morphological data were used to make predictions of fundamental frequency and subglottal pressure ranges. Such predictions agreed well with measurements from natural phonation and phonation of excised larynges, respectively. We assume that fat shapes Panthera vocal folds into an advantageous geometry for phonation and it protects vocal folds. Its primary function is probably not to increase vocal fold mass as suggested previously. The large square-shaped Panthera vocal fold eases phonation onset and thereby extends the dynamic range of the voice. PMID:22073246

Right- and left-handed three-helix proteins. I. Experimental and simulation analysis of differences in folding and structure.

PubMed

Glyakina, Anna V; Pereyaslavets, Leonid B; Galzitskaya, Oxana V

2013-09-01

Despite the large number of publications on three-helix protein folding, there is no study devoted to the influence of handedness on the rate of three-helix protein folding. From the experimental studies, we make a conclusion that the left-handed three-helix proteins fold faster than the right-handed ones. What may explain this difference? An important question arising in this paper is whether the modeling of protein folding can catch the difference between the protein folding rates of proteins with similar structures but with different folding mechanisms. To answer this question, the folding of eight three-helix proteins (four right-handed and four left-handed), which are similar in size, was modeled using the Monte Carlo and dynamic programming methods. The studies allowed us to determine the orders of folding of the secondary-structure elements in these domains and amino acid residues which are important for the folding. The obtained data are in good correlation with each other and with the experimental data. Structural analysis of these proteins demonstrated that the left-handed domains have a lesser number of contacts per residue and a smaller radius of cross section than the right-handed domains. This may be one of the explanations of the observed fact. The same tendency is observed for the large dataset consisting of 332 three-helix proteins (238 right- and 94 left-handed). From our analysis, we found that the left-handed three-helix proteins have some less-dense packing that should result in faster folding for some proteins as compared to the case of right-handed proteins. Copyright © 2013 Wiley Periodicals, Inc.

Preliminary enrichment and separation of genistein and apigenin from extracts of pigeon pea roots by macroporous resins.

PubMed

Liu, Wei; Zhang, Su; Zu, Yuan-Gang; Fu, Yu-Jie; Ma, Wei; Zhang, Dong-Yang; Kong, Yu; Li, Xiao-Juan

2010-06-01

Enrichment and separation of genistein and apigenin from extracts of pigeon pea roots were studied using eleven macroporous resins with different physical and chemical properties. ADS-5 resin showed the maximum effectiveness among the tested resins. The solute affinity towards ADS-5 resin at different temperatures was described in terms of Langmuir and Freundlich isotherms, and the equilibrium experimental data were well-fitted to the two isotherms. In order to optimize the operating parameters for separating genistein and apigenin, dynamic adsorption and desorption tests were carried out. After one run treatment with ADS-5 resin, the contents of genistein and apigenin in the product were 9.36-fold and 11.09-fold increased with recovery yields of 89.78% and 93.41%, respectively. The process achieved easy and effective enrichment and separation of genistein and apigenin by using ADS-5 resin, and it is a promising basis for large-scale preparation of genistein and apigenin from pigeon pea or other plants extracts. (c) 2010 Elsevier Ltd. All rights reserved.

Large-Scale Metabolomics Reveals A Complex Response of Aspergillus nidulans to Epigenetic Perturbation

PubMed Central

Albright, Jessica C.; Henke, Matthew T.; Soukup, Alexandra A.; McClure, Ryan A.; Thomson, Regan J.; Keller, Nancy P.; Kelleher, Neil L.

2015-01-01

The microbial world offers a rich source of bioactive compounds for those able to sift through it. Technologies capable of quantitatively detecting natural products while simultaneously identifying known compounds would expedite the search for new pharmaceutical leads. Prior efforts have targeted histone deacetylases in fungi to globally activate the production of new secondary metabolites, yet no study has directly assessed its effects with minimal bias at the metabolomic level. Using untargeted metabolomics, we monitored changes in >1000 small molecules secreted from the model fungus, Aspergillus nidulans, following genetic or chemical reductions in histone deacetylase activity (HDACi). Through quantitative, differential analyses, we found nearly equal numbers of compounds were up- and down-regulated by >100 fold. We detected products from both known and unknown biosynthetic pathways and discovered that A. nidulans is capable of producing fellutamides, proteasome inhibitors whose expression was induced by ~100 fold or greater upon HDACi. This work adds momentum to an ‘omics’-driven resurgence in natural products research, where direct detection replaces bioactivity as the primary screen for new pharmacophores. PMID:25815712

Development of a Highly Automated and Multiplexed Targeted Proteome Pipeline and Assay for 112 Rat Brain Synaptic Proteins

PubMed Central

Colangelo, Christopher M.; Ivosev, Gordana; Chung, Lisa; Abbott, Thomas; Shifman, Mark; Sakaue, Fumika; Cox, David; Kitchen, Rob R.; Burton, Lyle; Tate, Stephen A; Gulcicek, Erol; Bonner, Ron; Rinehart, Jesse; Nairn, Angus C.; Williams, Kenneth R.

2015-01-01

We present a comprehensive workflow for large scale (>1000 transitions/run) label-free LC-MRM proteome assays. Innovations include automated MRM transition selection, intelligent retention time scheduling (xMRM) that improves Signal/Noise by >2-fold, and automatic peak modeling. Improvements to data analysis include a novel Q/C metric, Normalized Group Area Ratio (NGAR), MLR normalization, weighted regression analysis, and data dissemination through the Yale Protein Expression Database. As a proof of principle we developed a robust 90 minute LC-MRM assay for Mouse/Rat Post-Synaptic Density (PSD) fractions which resulted in the routine quantification of 337 peptides from 112 proteins based on 15 observations per protein. Parallel analyses with stable isotope dilution peptide standards (SIS), demonstrate very high correlation in retention time (1.0) and protein fold change (0.94) between the label-free and SIS analyses. Overall, our first method achieved a technical CV of 11.4% with >97.5% of the 1697 transitions being quantified without user intervention, resulting in a highly efficient, robust, and single injection LC-MRM assay. PMID:25476245

Application of Fast Multipole Methods to the NASA Fast Scattering Code

NASA Technical Reports Server (NTRS)

Dunn, Mark H.; Tinetti, Ana F.

2008-01-01

The NASA Fast Scattering Code (FSC) is a versatile noise prediction program designed to conduct aeroacoustic noise reduction studies. The equivalent source method is used to solve an exterior Helmholtz boundary value problem with an impedance type boundary condition. The solution process in FSC v2.0 requires direct manipulation of a large, dense system of linear equations, limiting the applicability of the code to small scales and/or moderate excitation frequencies. Recent advances in the use of Fast Multipole Methods (FMM) for solving scattering problems, coupled with sparse linear algebra techniques, suggest that a substantial reduction in computer resource utilization over conventional solution approaches can be obtained. Implementation of the single level FMM (SLFMM) and a variant of the Conjugate Gradient Method (CGM) into the FSC is discussed in this paper. The culmination of this effort, FSC v3.0, was used to generate solutions for three configurations of interest. Benchmarking against previously obtained simulations indicate that a twenty-fold reduction in computational memory and up to a four-fold reduction in computer time have been achieved on a single processor.

Simplified in vitro refolding and purification of recombinant human granulocyte colony stimulating factor using protein folding cation exchange chromatography.

PubMed

Vemula, Sandeep; Dedaniya, Akshay; Thunuguntla, Rahul; Mallu, Maheswara Reddy; Parupudi, Pavani; Ronda, Srinivasa Reddy

2015-01-30

Protein folding-strong cation exchange chromatography (PF-SCX) has been employed for efficient refolding with simultaneous purification of recombinant human granulocyte colony stimulating factor (rhG-CSF). To acquire a soluble form of renatured and purified rhG-CSF, various chromatographic conditions, including the mobile phase composition and pH was evaluated. Additionally, the effects of additives such as urea, amino acids, polyols, sugars, oxidizing agents and their amalgamations were also investigated. Under the optimal conditions, rhG-CSF was efficaciously solubilized, refolded and simultaneously purified by SCX in a single step. The experimental results using ribose (2.0M) and arginine (0.6M) combination were found to be satisfactory with mass yield, purity and specific activity of 71%, ≥99% and 2.6×10(8)IU/mg respectively. Through this investigation, we concluded that the SCX refolding method was more efficient than conventional methods which has immense potential for the large-scale production of purified rhG-CSF. Copyright © 2014 Elsevier B.V. All rights reserved.

Codon usage bias in prokaryotic pyrimidine-ending codons is associated with the degeneracy of the encoded amino acids

PubMed Central

Wald, Naama; Alroy, Maya; Botzman, Maya; Margalit, Hanah

2012-01-01

Synonymous codons are unevenly distributed among genes, a phenomenon termed codon usage bias. Understanding the patterns of codon bias and the forces shaping them is a major step towards elucidating the adaptive advantage codon choice can confer at the level of individual genes and organisms. Here, we perform a large-scale analysis to assess codon usage bias pattern of pyrimidine-ending codons in highly expressed genes in prokaryotes. We find a bias pattern linked to the degeneracy of the encoded amino acid. Specifically, we show that codon-pairs that encode two- and three-fold degenerate amino acids are biased towards the C-ending codon while codons encoding four-fold degenerate amino acids are biased towards the U-ending codon. This codon usage pattern is widespread in prokaryotes, and its strength is correlated with translational selection both within and between organisms. We show that this bias is associated with an improved correspondence with the tRNA pool, avoidance of mis-incorporation errors during translation and moderate stability of codon–anticodon interaction, all consistent with more efficient translation. PMID:22581775

Anisotropic inflation with a non-minimally coupled electromagnetic field to gravity

NASA Astrophysics Data System (ADS)

Adak, Muzaffer; Akarsu, Özgür; Dereli, Tekin; Sert, Özcan

2017-11-01

We consider the non-minimal model of gravity in Y(R) F2-form. We investigate a particular case of the model, for which the higher order derivatives are eliminated but the scalar curvature R is kept to be dynamical via the constraint YRFmnFmn =-2/κ2. The effective fluid obtained can be represented by interacting electromagnetic field and vacuum depending on Y(R), namely, the energy density of the vacuum tracks R while energy density of the conventional electromagnetic field is dynamically scaled with the factor Y(R)/2. We give exact solutions for anisotropic inflation by assuming the volume scale factor of the Universe exhibits a power-law expansion. The directional scale factors do not necessarily exhibit power-law expansion, which would give rise to a constant expansion anisotropy, but expand non-trivially and give rise to a non-monotonically evolving expansion anisotropy that eventually converges to a non-zero constant. Relying on this fact, we discuss the anisotropic e-fold during the inflation by considering observed scale invariance in CMB and demanding the Universe to undergo the same amount of e-folds in all directions. We calculate the residual expansion anisotropy at the end of inflation, though as a result of non-monotonic behaviour of expansion anisotropy all the axes of the Universe undergo the same of amount of e-folds by the end of inflation. We also discuss the generation of the modified electromagnetic field during the first few e-folds of the inflation and its persistence against to the vacuum till end of inflation.

Connectivity-driven white matter scaling and folding in primate cerebral cortex

PubMed Central

Herculano-Houzel, Suzana; Mota, Bruno; Kaas, Jon H.

2010-01-01

Larger brains have an increasingly folded cerebral cortex whose white matter scales up faster than the gray matter. Here we analyze the cellular composition of the subcortical white matter in 11 primate species, including humans, and one Scandentia, and show that the mass of the white matter scales linearly across species with its number of nonneuronal cells, which is expected to be proportional to the total length of myelinated axons in the white matter. This result implies that the average axonal cross-section area in the white matter, a, does not scale significantly with the number of neurons in the gray matter, N. The surface area of the white matter increases with N0.87, not N1.0. Because this surface can be defined as the product of N, a, and the fraction n of cortical neurons connected through the white matter, we deduce that connectivity decreases in larger cerebral cortices as a slowly diminishing fraction of neurons, which varies with N−0.16, sends myelinated axons into the white matter. Decreased connectivity is compatible with previous suggestions that neurons in the cerebral cortex are connected as a small-world network and should slow down the increase in global conduction delay in cortices with larger numbers of neurons. Further, a simple model shows that connectivity and cortical folding are directly related across species. We offer a white matter-based mechanism to account for increased cortical folding across species, which we propose to be driven by connectivity-related tension in the white matter, pulling down on the gray matter. PMID:20956290

Tectonic Constraints on the Evolution of Geothermal Systems in the Central Andean Volcanic Zone (CAVZ)

NASA Astrophysics Data System (ADS)

Veloso, E. E.; Tardani, D.; Aron, F.; Elizalde, J. D.; Sanchez-Alfaro, P.; Godoy, B.

2017-12-01

South of 19°S, geothermal fields and Pliocene-to-Holocene volcanic centers of the Central Andean Volcanic Zone are spatially associated with distinct, large-scale fault systems disrupting the volcanic arc, which control the architecture and dynamics of the fluids reservoirs at shallow crustal levels. Based on an extensive compilation of structural, lithological and isotopic data, and satellite imagery band-ratio analyses, we produced detailed maps of 13 areas comprising 19 identified and/or potential geothermal fields, to examine if particular local-scale tectonic configurations are associated to fluids migrating from different crustal levels. We defined three main tectonic environments according to the specific, kilometer-scale structural arrangement and its spatial relation to the geothermal surface manifestations. T1, dominated by left-lateral, pure strike-slip motion on a NW-trending duplex-like geometry with geothermal fields located along the faults - in turn distributed into five major subparallel zones cutting across the orogenic belt between ca. 20° and 27°S. T2, dominated by shortening on a series of N-trending thrust faults and fault-propagated folds, cut and displaced by the above mentioned NW-trending faults, with geothermal fields hosted at fault intersections and at fold hinges. And T3, characterized by transtension accommodated by NW-to-WNW-trending left-lateral/normal faults, with hot-springs lying along the fault traces. Interestingly, each of the independently defined tectonic environments has distinctive helium (in fluids) and strontium (in lavas) isotopic signatures and estimated geothermal reservoir temperatures. T1 shows a large 4He contribution, low 87Sr/86Sr ratio and temperatures varying between ca. 220°-310°C; T3 low 4He and high 87Sr/86Sr ratio and temperature (260°-320°C); T2 isotopic values fall between T1 and T3, yet showing the lowest (130°-250°C) temperatures. We suggest that these particular isotopic signatures are due to a strong structural control on the hot reservoir location and meteoric water content, T3 allowing deeper hot fluid provenances and T1 more meteoric influx.

Fold-structure analysis of paleozoic rocks in the Variscan Harz Mountains (Lautenthal, Central Germany) based on laserscanning and 3D modelling

NASA Astrophysics Data System (ADS)

Wagner, Bianca; Leiss, Bernd; Stöpler, Ralf; Zahnow, Fabian

2017-04-01

Folded paleozoic sedimentary rocks of Upper Devonian to Lower Carboniferous age are very well exposed in the abandoned chert quarry of Lautenthal in the western Harz Mountains. The outcrop represents typical structures of the Rhenohercynian thrust and fold belt of the Variscan orogen and therefore allows quantitative studies for the understanding of e.g. fold mechanisms and the amount of shortening. The sequence is composed of alternating beds of cherts, shales and tuffites, which show varying thicknesses, undulating and thinning out of certain layers. Irregularly occurring lenses of greywackes are interpreted as sedimentary intrusions. The compressive deformation style is expressed by different similar and parallel fold structures at varying scales as well as small-scale reverse faults and triangle structures. An accurate mapping of the outcrop in the classical way is very challenging due to distant and unconnected outcrop parts with differing elevations and orientations. Furthermore, the visibility is limited because of nearby trees, diffuse vegetation cover and no available total view. Therefore, we used a FARO 120 3D laserscanner and Trimble GNSS device to generate a referenced and drawn to scale point cloud of the complete quarry. Based on the point cloud a geometric 3D model of prominent horizons and structural features of various sizes was constructed. Thereafter, we analyzed the structures in matters of orientation and deformation mechanisms. Finally, we applied a retrodeformation algorithm on the model to restore the original sedimentary sequence and to calculate shortening including the amount of pressure solution. Only digital mapping allows such a time-saving, accurate and especially complete 3D survey of this excellent study object. We demonstrated that such 3D-models enable spatial correlations with other complex structures cropping out in the area. Moreover, we confirmed that a structural upscaling to the 100 to 1000 m scale is much easier and much more instructive than it could have been done in the classical way.

A comparison of self-oscillating phonation models

NASA Astrophysics Data System (ADS)

McPhail, Michael; Campo, Elizabeth; Walters, Gage; Krane, Michael

2017-11-01

This talk presents a comparison of self-oscillating models of phonation. The goal is to assess how well synthetic rubber vocal folds reproduce the gross behavior of phonation. Data from molded rubber folds and a variety of excised mammalian larynges were collected from the literature and from the authors' physical model. Gross trends are discussed and a simple scaling is presented that appears to collapse these data. Finally, comparisons between molded rubber folds and excised larynges are highlighted. Acknowledge support from NIH DC R01005642-11.

Bi-stable vocal fold adduction: a mechanism of modal-falsetto register shifts and mixed registration.

PubMed

Titze, Ingo R

2014-04-01

The origin of vocal registers has generally been attributed to differential activation of cricothyroid and thyroarytenoid muscles in the larynx. Register shifts, however, have also been shown to be affected by glottal pressures exerted on vocal fold surfaces, which can change with loudness, pitch, and vowel. Here it is shown computationally and with empirical data that intraglottal pressures can change abruptly when glottal adductory geometry is changed relatively smoothly from convergent to divergent. An intermediate shape between large convergence and large divergence, namely, a nearly rectangular glottal shape with almost parallel vocal fold surfaces, is associated with mixed registration. It can be less stable than either of the highly angular shapes unless transglottal pressure is reduced and upper stiffness of vocal fold tissues is balanced with lower stiffness. This intermediate state of adduction is desirable because it leads to a low phonation threshold pressure with moderate vocal fold collision. Achieving mixed registration consistently across wide ranges of F0, lung pressure, and vocal tract shapes appears to be a balancing act of coordinating laryngeal muscle activation with vocal tract pressures. Surprisingly, a large transglottal pressure is not facilitative in this process, exacerbating the bi-stable condition and the associated register contrast.

Bi-stable vocal fold adduction: A mechanism of modal-falsetto register shifts and mixed registration

PubMed Central

Titze, Ingo R.

2014-01-01

The origin of vocal registers has generally been attributed to differential activation of cricothyroid and thyroarytenoid muscles in the larynx. Register shifts, however, have also been shown to be affected by glottal pressures exerted on vocal fold surfaces, which can change with loudness, pitch, and vowel. Here it is shown computationally and with empirical data that intraglottal pressures can change abruptly when glottal adductory geometry is changed relatively smoothly from convergent to divergent. An intermediate shape between large convergence and large divergence, namely, a nearly rectangular glottal shape with almost parallel vocal fold surfaces, is associated with mixed registration. It can be less stable than either of the highly angular shapes unless transglottal pressure is reduced and upper stiffness of vocal fold tissues is balanced with lower stiffness. This intermediate state of adduction is desirable because it leads to a low phonation threshold pressure with moderate vocal fold collision. Achieving mixed registration consistently across wide ranges of F0, lung pressure, and vocal tract shapes appears to be a balancing act of coordinating laryngeal muscle activation with vocal tract pressures. Surprisingly, a large transglottal pressure is not facilitative in this process, exacerbating the bi-stable condition and the associated register contrast. PMID:25235006

Parallel Optimization of 3D Cardiac Electrophysiological Model Using GPU

PubMed Central

Xia, Yong; Zhang, Henggui

2015-01-01

Large-scale 3D virtual heart model simulations are highly demanding in computational resources. This imposes a big challenge to the traditional computation resources based on CPU environment, which already cannot meet the requirement of the whole computation demands or are not easily available due to expensive costs. GPU as a parallel computing environment therefore provides an alternative to solve the large-scale computational problems of whole heart modeling. In this study, using a 3D sheep atrial model as a test bed, we developed a GPU-based simulation algorithm to simulate the conduction of electrical excitation waves in the 3D atria. In the GPU algorithm, a multicellular tissue model was split into two components: one is the single cell model (ordinary differential equation) and the other is the diffusion term of the monodomain model (partial differential equation). Such a decoupling enabled realization of the GPU parallel algorithm. Furthermore, several optimization strategies were proposed based on the features of the virtual heart model, which enabled a 200-fold speedup as compared to a CPU implementation. In conclusion, an optimized GPU algorithm has been developed that provides an economic and powerful platform for 3D whole heart simulations. PMID:26581957

Parallel Optimization of 3D Cardiac Electrophysiological Model Using GPU.

PubMed

Xia, Yong; Wang, Kuanquan; Zhang, Henggui

2015-01-01

Large-scale 3D virtual heart model simulations are highly demanding in computational resources. This imposes a big challenge to the traditional computation resources based on CPU environment, which already cannot meet the requirement of the whole computation demands or are not easily available due to expensive costs. GPU as a parallel computing environment therefore provides an alternative to solve the large-scale computational problems of whole heart modeling. In this study, using a 3D sheep atrial model as a test bed, we developed a GPU-based simulation algorithm to simulate the conduction of electrical excitation waves in the 3D atria. In the GPU algorithm, a multicellular tissue model was split into two components: one is the single cell model (ordinary differential equation) and the other is the diffusion term of the monodomain model (partial differential equation). Such a decoupling enabled realization of the GPU parallel algorithm. Furthermore, several optimization strategies were proposed based on the features of the virtual heart model, which enabled a 200-fold speedup as compared to a CPU implementation. In conclusion, an optimized GPU algorithm has been developed that provides an economic and powerful platform for 3D whole heart simulations.

Codigestion of manure and organic wastes in centralized biogas plants: status and future trends.

PubMed

Angelidaki, I; Ellegaard, L

2003-01-01

Centralized biogas plants in Denmark codigest mainly manure, together with other organic waste such as industrial organic waste, source sorted household waste, and sewage sludge. Today 22 large-scale centralized biogas plants are in operation in Denmark, and in 2001 they treated approx 1.2 million tons of manure as well as approx 300,000 of organic industrial waste. Besides the centralized biogas plants there are a large number of smaller farm-scale plants. The long-term energy plan objective is a 10-fold increase of the 1998 level of biogas production by the year 2020. This will help to achieve a target of 12-14% of the national energy consumption being provided by renewable energy by the year 2005 and 33% by the year 2030. A major part of this increase is expected to come from new centralized biogas plants. The annual potential for biogas production from biomass resources available in Denmark is estimated to be approx 30 Peta Joule (PJ). Manure comprises about 80% of this potential. Special emphasis has been paid to establishing good sanitation and pathogen reduction of the digested material, to avoid risk of spreading pathogens when applying the digested manure as fertilizer to agricultural soils.

High-resolution simulation of deep pencil beam surveys - analysis of quasi-periodicity

NASA Astrophysics Data System (ADS)

Weiss, A. G.; Buchert, T.

1993-07-01

We carry out pencil beam constructions in a high-resolution simulation of the large-scale structure of galaxies. The initial density fluctuations are taken to have a truncated power spectrum. All the models have {OMEGA} = 1. As an example we present the results for the case of "Hot-Dark-Matter" (HDM) initial conditions with scale-free n = 1 power index on large scales as a representative of models with sufficient large-scale power. We use an analytic approximation for particle trajectories of a self-gravitating dust continuum and apply a local dynamical biasing of volume elements to identify luminous matter in the model. Using this method, we are able to resolve formally a simulation box of 1200h^-1^ Mpc (e.g. for HDM initial conditions) down to the scale of galactic halos using 2160^3^ particles. We consider this as the minimal resolution necessary for a sensible simulation of deep pencil beam data. Pencil beam probes are taken for a given epoch using the parameters of observed beams. In particular, our analysis concentrates on the detection of a quasi-periodicity in the beam probes using several different methods. The resulting beam ensembles are analyzed statistically using number distributions, pair-count histograms, unnormalized pair-counts, power spectrum analysis and trial-period folding. Periodicities are classified according to their significance level in the power spectrum of the beams. The simulation is designed for application to parameter studies which prepare future observational projects. We find that a large percentage of the beams show quasi- periodicities with periods which cluster at a certain length scale. The periods found range between one and eight times the cutoff length in the initial fluctuation spectrum. At significance levels similar to those of the data of Broadhurst et al. (1990), we find about 15% of the pencil beams to show periodicities, about 30% of which are around the mean separation of rich clusters, while the distribution of scales reaches values of more than 200h^-1^ Mpc. The detection of periodicities larger than the typical void size must not be due to missing of "walls" (like the so called "Great Wall" seen in the CfA catalogue of galaxies), but can be due to different clustering properties of galaxies along the beams.

Functional Advantages of Conserved Intrinsic Disorder in RNA-Binding Proteins.

PubMed

Varadi, Mihaly; Zsolyomi, Fruzsina; Guharoy, Mainak; Tompa, Peter

2015-01-01

Proteins form large macromolecular assemblies with RNA that govern essential molecular processes. RNA-binding proteins have often been associated with conformational flexibility, yet the extent and functional implications of their intrinsic disorder have never been fully assessed. Here, through large-scale analysis of comprehensive protein sequence and structure datasets we demonstrate the prevalence of intrinsic structural disorder in RNA-binding proteins and domains. We addressed their functionality through a quantitative description of the evolutionary conservation of disordered segments involved in binding, and investigated the structural implications of flexibility in terms of conformational stability and interface formation. We conclude that the functional role of intrinsically disordered protein segments in RNA-binding is two-fold: first, these regions establish extended, conserved electrostatic interfaces with RNAs via induced fit. Second, conformational flexibility enables them to target different RNA partners, providing multi-functionality, while also ensuring specificity. These findings emphasize the functional importance of intrinsically disordered regions in RNA-binding proteins.

Seismic cycle feedbacks in a mid-crustal shear zone

NASA Astrophysics Data System (ADS)

Melosh, Benjamin L.; Rowe, Christie D.; Gerbi, Christopher; Smit, Louis; Macey, Paul

2018-07-01

Mid-crustal fault rheology is controlled by alternating brittle and plastic deformation mechanisms, which cause feedback cycles that influence earthquake behavior. Detailed mapping and microstructural observations in the Pofadder Shear Zone (Namibia and South Africa) reveal a lithologically heterogeneous shear zone core with quartz-rich mylonites and ultramylonites, plastically overprinted pseudotachylyte and active shear folds. We present evidence for a positive feedback cycle in which coseismic grain size reduction facilitates active shear folding by enhancing competency contrasts and promoting crystal plastic flow. Shear folding strengthens a portion of a shear zone by limb rotation, focusing deformation and promoting plastic flow or brittle slip in resulting areas of localized high stress. Using quartz paleopiezometry, we estimate strain and slip rates consistent with other studies of exhumed shear zones and modern plate boundary faults, helping establish the Pofadder Shear Zone as an ancient analogue to modern, continental-scale, strike-slip faults. This feedback cycle influences seismicity patterns at the scale of study (10s of meters) and possibly larger scales as well, and contributes to bulk strengthening of the brittle-plastic transition on modern plate boundary faults.

Critical transition to bistability arising from hidden degrees of freedom in origami structures

NASA Astrophysics Data System (ADS)

Cohen, Itai; Silverberg, Jesse; Na, Jun-Hee; Evans, Arthur; Liu, Bin; Hull, Thomas; Santangelo, Christian; Lang, Robert; Hayward, Ryan

2015-03-01

Origami, the traditional art of paper folding, is now being used to design responsive, dynamic, and customizable mechanical metamaterials. The remarkable abilities of these origami-inspired devices emerge from a predefined crease pattern, which couples kinematic folding constraints to the geometric placement of creases. In spite of this progress, a generalized physical understanding of origami remains elusive due to the challenge in determining whether local kinematic constraints are globally compatible, and an incomplete understanding of how bending and crease plasticity found in real materials contribute to the overall mechanical response. Here, we show experimentally and theoretically that the traditional square twist, whose crease pattern has zero degrees of freedom (DOF) and therefore should not be foldable, is nevertheless able to be folded by accessing higher energy scale deformations associated with bending. Due to the separation of bending and crease energy scales, these hidden DOF lead to a geometrically-driven critical bifurcation between mono- and bistability. The scale-free geometric underpinnings of this physical phenomenon suggest a generalized design principle that can be useful for fabricating micro- and nanoscale mechanical switches.

Estimating Rheological Parameters of Anhydrite from Folded Evaporite sequences: Implications for Internal Dynamics of Salt Structure

NASA Astrophysics Data System (ADS)

Adamuszek, Marta; Dabrowski, Marcin; Schmalholz, Stefan M.; Urai, Janos L.; Raith, Alexander

2015-04-01

Salt structures have been identified as a potential target for hydrocarbon, CO2, or radioactive waste storage. The most suitable locations for magazines are considered in the thick and relatively homogeneous rock salt layers. However, salt structures often consist of the evaporite sequence including rock salt intercalated with other rock types e.g.: anhydrite, gypsum, potassium and magnesium salt, calcite, dolomite, or shale. The presence of such heterogeneities causes a serious disturbance in the structure management. Detailed analysis of the internal architecture and internal dynamics of the salt structure are crucial for evaluating them as suitable repositories and also their long-term stability. The goal of this study is to analyse the influence of the presence of anhydrite layers on the internal dynamics of salt structures. Anhydrite is a common rock in evaporite sequences. Its physical and mechanical properties strongly differ from the properties of rock salt. The density of anhydrite is much higher than the density of salt, thus anhydrite is likely to sink in salt causing the disturbance of the surrounding structures. This suggestion was the starting point to the discussion about the long-term stability of the magazines in salt structures [1]. However, the other important parameter that has to be taken into account is the viscosity of anhydrite. The high viscosity ratio between salt and anhydrite can restrain the layer from sinking. The rheological behaviour of anhydrite has been studied in laboratory experiments [2], but the results only provide information about the short-term behaviour. The long-term behaviour can be best predicted using indirect methods e.g. based on the analysis of natural structures that developed over geological time scale. One of the most promising are fold structures, the shape of which is very sensitive to the rheological parameters of the deforming materials. Folds can develop in mechanically stratified materials during layer parallel shortening. Mechanical model have been developed to rigorously correlate rheological properties of rock to the fold shape. A quantitative fold shape analysis combined with the folding theory allows deciphering the rock rheology. In this study, we analyse anhydrite layers embedded in the rock salt from the Upper Permian Zechstein salt formation from Dutch offshore. The anhydrite layers are common intercalation in the sequence. Their thickness varies between few millimetres up to hundred meters. The layers are strongly deformed often forming fold structures, which can be observed on a wide range of scales: in core samples, mine galleries, and also in the seismic sections. For our analysis, we select single layer fold trains. Quantitative fold shape analysis is carried out using Fold Geometry Toolbox [3], which allows deciphering the viscosity ratio between anhydrite and salt. The results indicate that anhydrite layer is ca. 10 to 30 times more viscous than the embedding salt. Further, we use the estimated rheological parameters of anhydrite in the numerical analysis of the internal salt dynamics. We solve an incompressible Stokes equation in the presence of the gravity using the finite element method solver MILAMIN [4]. We show that the presence of denser and more viscous anhydrite layers in the tectonically stable regime is insignificant for the internal stability of the salt structures. [1] Chemia, Z., Koyi, H., Schmeling, H. 2008. Numerical modelling of rise and fall of a dense layer in salt diapirs. Geophysical Journal International, 172: 798-816. [2] Muller, W.H., Briegel, U. 1978. The rheological behaviour of polycrystalline Anhydrite. Eclogae Geol. Helv, 71(2): 397-407 [3] Adamuszek M., Schmid D.W., Dabrowski M. 2011. Fold geometry toolbox - Automated determination of fold shape, shortening, and material properties, Journal of Structural Geology, 33: 1406-1416. [4] Dabrowski, M., Krotkiewski, M., and Schmid, D. W. 2008. MILAMIN: MATLAB-based finite element method solver for large problems. Geochemistry Geophysics Geosystems, 9: Q04030.

Dynamics of proteins aggregation. I. Universal scaling in unbounded media

NASA Astrophysics Data System (ADS)

Zheng, Size; Javidpour, Leili; Shing, Katherine S.; Sahimi, Muhammad

2016-10-01

It is well understood that in some cases proteins do not fold correctly and, depending on their environment, even properly-folded proteins change their conformation spontaneously, taking on a misfolded state that leads to protein aggregation and formation of large aggregates. An important factor that contributes to the aggregation is the interactions between the misfolded proteins. Depending on the aggregation environment, the aggregates may take on various shapes forming larger structures, such as protein plaques that are often toxic. Their deposition in tissues is a major contributing factor to many neuro-degenerative diseases, such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, and prion. This paper represents the first part in a series devoted to molecular simulation of protein aggregation. We use the PRIME, a meso-scale model of proteins, together with extensive discontinuous molecular dynamics simulation to study the aggregation process in an unbounded fluid system, as the first step toward MD simulation of the same phenomenon in crowded cellular environments. Various properties of the aggregates have been computed, including dynamic evolution of aggregate-size distribution, mean aggregate size, number of peptides that contribute to the formation of β sheets, number of various types of hydrogen bonds formed in the system, radius of gyration of the aggregates, and the aggregates' diffusivity. We show that many of such quantities follow dynamic scaling, similar to those for aggregation of colloidal clusters. In particular, at long times the mean aggregate size S(t) grows with time as, S(t) ˜ tz, where z is the dynamic exponent. To our knowledge, this is the first time that the qualitative similarity between aggregation of proteins and colloidal aggregates has been pointed out.

Geosphere - Cryosphere Interactions in the Saint Elias orogen, Alaska and Yukon (Invited)

NASA Astrophysics Data System (ADS)

Bruhn, R. L.; Sauber, J. M.; Forster, R. R.; Cotton, M. M.

2009-12-01

North America's largest alpine and piedmont glaciers occur in the Saint Elias orogen, where microplate collision together with the transition from transform faulting to subduction along the North American plate boundary, create extreme topographic relief, unusually high annual precipitation by orographic lift, and crustal displacements induced by both tectonic and glacio-isostatic deformation. Lithosphere-scale structure dominates the spatial pattern of glaciation; the piedmont Bering and Agassiz-Malaspina glaciers lay along deeply eroded troughs where reverse faults rise from the underlying Aleutian megathrust. The alpine Seward and Bagley Ice Valley glaciers flow along an early Tertiary plate boundary that has been reactivated by reverse faulting, and also by dextral shearing at the NW end of the Fairweather transform fault. Folding above a crustal-scale fault ramp near Icy Bay localizes orographic uplift of air masses, creating alpine glaciers that spill off the highlands into large ice falls, and rapidly dissect evolving structure by erosion. The rate and orientation of ice surface velocities, and the location of crevassing and folding partly reflect changes in basal topography of the glaciers caused by differential erosion of strata, and juxtaposition of variably oriented structures across faults. The effects of basal topography on ice flow are investigated using remote sensing measurements and analog models of glacier flow over uneven topography. Deformation of the ice in turn affects englacial hydrology and sub-ice fluvial systems, potentially impacting ice mass balance, on-set of surging, and loci of glacier quakes. The glaciers impact tectonics by localizing uplift and exhumation within the orogen, and modulating tectonic stress fields as ice masses wax and wane. This is particularly evident in crustal seismicity rates at annual to decadal time scales, while stratigraphy of coastal terraces record both earthquake deformation and glacial isostasy over millennia.

Coseismic fold scarp associated with historic earthquakes upon the Yoro active blind thrust, the Nobi-Ise fault zone, central Japan

NASA Astrophysics Data System (ADS)

Ishiyama, T.; Mueller, K.; Togo, M.

2004-12-01

We present structural models constrained by tectonic geomorphology, surface geologic mapping, shallow borehole transects and a high-resolution S-wave seismic reflection profile to define the kinematic evolution of a coseismic fold scarp along the Nobi-Ise fault zone (NIFZ). The NIFZ is an active intraplate fault system in central Japan, and consists of a 110-km-long array of active, east-verging reverse faults. Fold scarps along the Yoro fault are interpreted as produced during a large historic blind-thrust earthquake. The Yoro Mountains form the stripped core of the largest structure in the NIFZ and expose Triassic-Jurassic basement that are thrust eastward over a 2-km-thick sequence of Pliocene-Pleistocene strata deposited in the Nobi basin. This basement-cored fold is underlain by an active blind thrust that is expressed as late Holocene fold scarps along its eastern flank. Drilling investigations across the fold scarp at a site near Shizu identified at least three episodes of active folding associated with large earthquakes on the Yoro fault. Radiocarbon ages constrain the latest event as having occurred in a period that contains historical evidence for a large earthquake in A.D. 1586. A high resolution, S-wave seismic reflection profile at the same site shows that the topographic fold scarp coincides with the projected surface trace of the synclinal axis, across which the buried, early Holocene to historic sedimentary units are folded. This is interpreted to indicate that the structure accommodated coseismic fault-propagation folding during the A.D. 1586 blind thrust earthquake. Flexural-slip folding associated with secondary bedding-parallel thrusts may also deform late Holocene strata and act to consume slip on the primary blind thrust across the synclinal axial surfaces. The best-fitting trishear model for folded ca. 13 ka gravels deposited across the forelimb requires a 28\\deg east-dipping thrust fault. This solution suggests that a 4.2 mm/yr of slip rate has been accommodated on the Yoro fault during the late Holocene, with an average vertical rate of 1.9 mm/yr. This is consistent with longer-term slip rates calculated by a structural relief across a ca. 7.3 ka volcanic ash horizon (1.6 mm/yr), and ca. 110 ka innerbay clays (1.3 mm/yr) deposited across the forelimb. Our trishear model is thus able to account for the bulk of the folding history accommodated at shorter millennial timescales, suggesting that this technique may be used to adequately define slip rates on blind thrust faults.

Destruction of the North China Craton: Lithosphere folding-induced removal of lithospheric mantle?

NASA Astrophysics Data System (ADS)

Zhang, Kai-Jun

2012-01-01

High heat flow, high surface topography, and widespread volcanism indicate that the lithospheric mantle of typical cratonic character of the North China Craton has been seriously destroyed in its eastern half. However, the mechanism of this process remains open to intense debate. Here lithosphere folding-induced lithospheric mantle removal is proposed as a new mechanism for the destruction of the craton. Four main NNE-SSW-striking lithospheric-scale anticlines and synclines are recognized within North China east of the Helan fold-and-thrust belt. The lithosphere folding occurred possibly during the Late Triassic through Jurassic when the Yangzi Craton collided with the North China Craton. It was accompanied or followed by lithospheric dripping, and could have possibly induced the lithosphere foundering of the North China Craton. The lithosphere folding would have modified the lithosphere morphology, creating significant undulation in the lithospheric base and thus causing variations of the patterns of the small-scale convection. It also could have provoked the formation of new shear zones liable to impregnation of magma, producing linear incisions at the cratonic base and resulting in foundering of lithospheric mantle blocks. Furthermore, it generated thickening of the lithosphere or the lower crust and initiated the destabilization and subsequent removal of the lithospheric mantle.

Exploring the Sequence-based Prediction of Folding Initiation Sites in Proteins.

PubMed

Raimondi, Daniele; Orlando, Gabriele; Pancsa, Rita; Khan, Taushif; Vranken, Wim F

2017-08-18

Protein folding is a complex process that can lead to disease when it fails. Especially poorly understood are the very early stages of protein folding, which are likely defined by intrinsic local interactions between amino acids close to each other in the protein sequence. We here present EFoldMine, a method that predicts, from the primary amino acid sequence of a protein, which amino acids are likely involved in early folding events. The method is based on early folding data from hydrogen deuterium exchange (HDX) data from NMR pulsed labelling experiments, and uses backbone and sidechain dynamics as well as secondary structure propensities as features. The EFoldMine predictions give insights into the folding process, as illustrated by a qualitative comparison with independent experimental observations. Furthermore, on a quantitative proteome scale, the predicted early folding residues tend to become the residues that interact the most in the folded structure, and they are often residues that display evolutionary covariation. The connection of the EFoldMine predictions with both folding pathway data and the folded protein structure suggests that the initial statistical behavior of the protein chain with respect to local structure formation has a lasting effect on its subsequent states.

Symmetric waterbomb origami.

PubMed

Chen, Yan; Feng, Huijuan; Ma, Jiayao; Peng, Rui; You, Zhong

2016-06-01

The traditional waterbomb origami, produced from a pattern consisting of a series of vertices where six creases meet, is one of the most widely used origami patterns. From a rigid origami viewpoint, it generally has multiple degrees of freedom, but when the pattern is folded symmetrically, the mobility reduces to one. This paper presents a thorough kinematic investigation on symmetric folding of the waterbomb pattern. It has been found that the pattern can have two folding paths under certain circumstance. Moreover, the pattern can be used to fold thick panels. Not only do the additional constraints imposed to fold the thick panels lead to single degree of freedom folding, but the folding process is also kinematically equivalent to the origami of zero-thickness sheets. The findings pave the way for the pattern being readily used to fold deployable structures ranging from flat roofs to large solar panels.

Experimental Approaches for Solution X-Ray Scattering and Fiber Diffraction

PubMed Central

Irving, T. C.

2008-01-01

X-ray scattering and diffraction from non-crystalline systems have gained renewed interest in recent years, as focus shifts from the structural chemistry information gained by high-resolution studies to the context of structural physiology at larger length scales. Such techniques permit the study of isolated macromolecules as well as highly organized macromolecular assemblies as a whole under near-physiological conditions. Time-resolved approaches, made possible by advanced synchrotron instrumentation, add a critical dimension to many of these investigations. This article reviews experimental approaches in non-crystalline x-ray scattering and diffraction that may be used to illuminate important scientific questions such as protein/nucleic acid folding and structure-function relationships in large macromolecular assemblies. PMID:18801437

Simulating chemistry using quantum computers.

PubMed

Kassal, Ivan; Whitfield, James D; Perdomo-Ortiz, Alejandro; Yung, Man-Hong; Aspuru-Guzik, Alán

2011-01-01

The difficulty of simulating quantum systems, well known to quantum chemists, prompted the idea of quantum computation. One can avoid the steep scaling associated with the exact simulation of increasingly large quantum systems on conventional computers, by mapping the quantum system to another, more controllable one. In this review, we discuss to what extent the ideas in quantum computation, now a well-established field, have been applied to chemical problems. We describe algorithms that achieve significant advantages for the electronic-structure problem, the simulation of chemical dynamics, protein folding, and other tasks. Although theory is still ahead of experiment, we outline recent advances that have led to the first chemical calculations on small quantum information processors.

Container-based sanitation: assessing costs and effectiveness of excreta management in Cap Haitien, Haiti

PubMed Central

Tilmans, Sebastien; Russel, Kory; Sklar, Rachel; Page, Leah; Kramer, Sasha

2015-01-01

Container-based sanitation (CBS) – in which wastes are captured in sealable containers that are then transported to treatment facilities – is an alternative sanitation option in urban areas where on-site sanitation and sewerage are infeasible. This paper presents the results of a pilot household CBS service in Cap Haitien, Haiti. We quantify the excreta generated weekly in a dense urban slum,(1) the proportion safely removed via container-based public and household toilets, and the costs associated with these systems. The CBS service yielded an approximately 3.5-fold decrease in the unmanaged share of faeces produced, and nearly eliminated the reported use of open defecation and “flying toilets” among service recipients. The costs of this pilot small-scale service were higher than those of large-scale waterborne sewerage, but economies of scale have the potential to reduce CBS costs over time. The paper concludes with a discussion of planning and policy implications of incorporating CBS into the menu of sanitation options for rapidly growing cities. PMID:26097288

Calibration of BCR-ABL1 mRNA quantification methods using genetic reference materials is a valid strategy to report results on the international scale.

PubMed

Mauté, Carole; Nibourel, Olivier; Réa, Delphine; Coiteux, Valérie; Grardel, Nathalie; Preudhomme, Claude; Cayuela, Jean-Michel

2014-09-01

Until recently, diagnostic laboratories that wanted to report on the international scale had limited options: they had to align their BCR-ABL1 quantification methods through a sample exchange with a reference laboratory to derive a conversion factor. However, commercial methods calibrated on the World Health Organization genetic reference panel are now available. We report results from a study designed to assess the comparability of the two alignment strategies. Sixty follow-up samples from chronic myeloid leukemia patients were included. Two commercial methods calibrated on the genetic reference panel were compared to two conversion factor methods routinely used at Saint-Louis Hospital, Paris, and at Lille University Hospital. Results were matched against concordance criteria (i.e., obtaining at least two of the three following landmarks: 50, 75 and 90% of the patient samples within a 2-fold, 3-fold and 5-fold range, respectively). Out of the 60 samples, more than 32 were available for comparison. Compared to the conversion factor method, the two commercial methods were within a 2-fold, 3-fold and 5-fold range for 53 and 59%, 89 and 88%, 100 and 97%, respectively of the samples analyzed at Saint-Louis. At Lille, results were 45 and 85%, 76 and 97%, 100 and 100%, respectively. Agreements between methods were observed in the four comparisons performed. Our data show that the two commercial methods selected are concordant with the conversion factor methods. This study brings the proof of principle that alignment on the international scale using the genetic reference panel is compatible with the patient sample exchange procedure. We believe that these results are particularly important for diagnostic laboratories wishing to adopt commercial methods. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Folding and Fracturing of Rocks: the background

NASA Astrophysics Data System (ADS)

Ramsay, John G.

2017-04-01

This book was generated by structural geology teaching classes at Imperial College. I was appointed lecturer during 1957 and worked together with Dr Gilbert Wilson teaching basic structural geology at B.Sc level. I became convinced that the subject, being essentially based on geometric field observations, required a firm mathematical basis for its future development. In particular it seemed to me to require a very sound understanding of stress and strain. My field experience suggested that a knowledge of two- and three-demensional strain was critical in understanding natural tectonic processes. I found a rich confirmation for this in early publications of deformed fossils, oolitic limestones and spotted slates made by several geologists around the beginning of the 20th century (Sorby, Philips, Haughton, Harker) often using surprisingly sophisticated mathematical methods. These methods were discussed and elaborated in Folding and Fracturing of Rocks in a practical way. The geometric features of folds were related to folding mechanisms and the fold related small scale structures such as cleavage, schistosity and lineation explained in terms of rock strain. My work in the Scottish Highlands had shown just how repeated fold superposition could produce very complex geometric features, while further work in other localities suggested that such geometric complications are common in many orogenic zones. From the development of structural geological studies over the past decades it seems that the readers of this book have found many of the ideas set out are still of practical application. The mapping of these outcrop-scale structures should be emphasised in all field studies because they can be seen as ''fingerprints'' of regional scale tectonic processes. My own understanding of structural geology has been inspired by field work and I am of the opinion that future progress in understanding will be likewise based on careful observation and measurement of the features of naturally deformed rocks mathematically analysed using the concepts of three-dimensional continuum mechanics.

Directional semivariogram analysis to identify and rank controls on the spatial variability of fracture networks

NASA Astrophysics Data System (ADS)

Hanke, John R.; Fischer, Mark P.; Pollyea, Ryan M.

2018-03-01

In this study, the directional semivariogram is deployed to investigate the spatial variability of map-scale fracture network attributes in the Paradox Basin, Utah. The relative variability ratio (R) is introduced as the ratio of integrated anisotropic semivariogram models, and R is shown to be an effective metric for quantifying the magnitude of spatial variability for any two azimuthal directions. R is applied to a GIS-based data set comprising roughly 1200 fractures, in an area which is bounded by a map-scale anticline and a km-scale normal fault. This analysis reveals that proximity to the fault strongly influences the magnitude of spatial variability for both fracture intensity and intersection density within 1-2 km. Additionally, there is significant anisotropy in the spatial variability, which is correlated with trends of the anticline and fault. The direction of minimum spatial correlation is normal to the fault at proximal distances, and gradually rotates and becomes subparallel to the fold axis over the same 1-2 km distance away from the fault. We interpret these changes to reflect varying scales of influence of the fault and the fold on fracture network development: the fault locally influences the magnitude and variability of fracture network attributes, whereas the fold sets the background level and structure of directional variability.

Mid-crustal flow during Tertiary extension in the Ruby Mountains core complex, Nevada

USGS Publications Warehouse

MacCready, T.; Snoke, A.W.; Wright, J.E.; Howard, K.A.

1997-01-01

Structural analysis and geochronologic data indicate a nearly orthogonal, late Eocene-Oligocene flow pattern in migmatitic infrastructure immediately beneath the kilometer-thick, extensional, mylonitic shear zone of the Ruby Mountains metamorphic core complex, Nevada. New U-Pb radiometric dating indicates that the development of a northward-trending lineation in the infrastructure is partly coeval with the development of a pervasive, west-northwest-trending lineation in the mylonitic shear zone. U-Pb monazite data from the leucogranite orthogneiss of Thorpe Creek indicate a crystallization age of ca. 36-39 Ma. Zircon fractions from a biotite monzogranite dike yield an age of ca. 29 Ma. The three dated samples from these units exhibit a penetrative, approximately north-south-trending elongation lineation. This lineation is commonly defined by oriented bundles of sillimanite and/or elongated aggregates of quartz and feldspar, indicating a synmetamorphic and syndeformational origin. The elongation lineation can be interpreted as a slip line in the flow plane of the migmatitic, nonmylonitic infrastructural core of the northern Ruby Mountains. A portion of this midcrustal flow is coeval with the well-documented, west-northwest sense of slip in the structurally overlying kilometer-thick, mid-Tertiary mylonitic shear zone. Lineations in the mylonitic zone are orthogonal to those in the deeper infrastructure, suggesting fundamental plastic decoupling between structural levels in this core complex. Furthermore, the infrastructure is characterized by overlapping, oppositely verging fold nappes, which are rooted to the east and west. One of the nappes may be synkinematic with the intrusion of the late Eocene orthogneiss of Thorpe Creek. In addition, the penetrative, elongation lineation in the infrastructure is subparallel to hinge lines of parasitic folds developed synchronous with the fold nappes, suggesting a kinematically related evolution. The area is evaluated in terms of a whole-crust extension model. Magmatic underplating in the lower crust stimulated the production of late Eocene-early Oligocene granitic magmas, which invaded metasedimentary and Mesozoic granitic rocks of the middle crust. The midcrustal rocks, weakened by the magmatic heat influx, acted as a low-viscosity compensating material, decoupled from an extending upper crust. The fold nappes and lineation trends suggest large-scale flow of the weakened crust into the study area. The inflow pattern in the migmatitic infrastructure can be interpreted as a manifestation of midcrustal migration into an area beneath a domain of highly extended upper trustai rocks. At present the inferred Eocene-early Oligocene phase of upper-crust extension remains unknown, but available data on relative and geochronologic timing are not inconsistent with our model of return flow into an area already undergoing large-scale upper-crustal extension.

A puzzle assembly strategy for fabrication of large engineered cartilage tissue constructs.

PubMed

Nover, Adam B; Jones, Brian K; Yu, William T; Donovan, Daniel S; Podolnick, Jeremy D; Cook, James L; Ateshian, Gerard A; Hung, Clark T

2016-03-21

Engineering of large articular cartilage tissue constructs remains a challenge as tissue growth is limited by nutrient diffusion. Here, a novel strategy is investigated, generating large constructs through the assembly of individually cultured, interlocking, smaller puzzle-shaped subunits. These constructs can be engineered consistently with more desirable mechanical and biochemical properties than larger constructs (~4-fold greater Young׳s modulus). A failure testing technique was developed to evaluate the physiologic functionality of constructs, which were cultured as individual subunits for 28 days, then assembled and cultured for an additional 21-35 days. Assembled puzzle constructs withstood large deformations (40-50% compressive strain) prior to failure. Their ability to withstand physiologic loads may be enhanced by increases in subunit strength and assembled culture time. A nude mouse model was utilized to show biocompatibility and fusion of assembled puzzle pieces in vivo. Overall, the technique offers a novel, effective approach to scaling up engineered tissues and may be combined with other techniques and/or applied to the engineering of other tissues. Future studies will aim to optimize this system in an effort to engineer and integrate robust subunits to fill large defects. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Puzzle Assembly Strategy for Fabrication of Large Engineered Cartilage Tissue Constructs

PubMed Central

Nover, Adam B.; Jones, Brian K.; Yu, William T.; Donovan, Daniel S.; Podolnick, Jeremy D.; Cook, James L.; Ateshian, Gerard A.; Hung, Clark T.

2016-01-01

Engineering of large articular cartilage tissue constructs remains a challenge as tissue growth is limited by nutrient diffusion. Here, a novel strategy is investigated, generating large constructs through the assembly of individually cultured, interlocking, smaller puzzle-shaped subunits. These constructs can be engineered consistently with more desirable mechanical and biochemical properties than larger constructs (~4-fold greater Young's modulus). A failure testing technique was developed to evaluate the physiologic functionality of constructs, which were cultured as individual subunits for 28 days, then assembled and cultured for an additional 21-35 days. Assembled puzzle constructs withstood large deformations (40-50% compressive strain) prior to failure. Their ability to withstand physiologic loads may be enhanced by increases in subunit strength and assembled culture time. A nude mouse model was utilized to show biocompatibility and fusion of assembled puzzle pieces in vivo. Overall, the technique offers a novel, effective approach to scaling up engineered tissues and may be combined with other techniques and/or applied to the engineering of other tissues. Future studies will aim to optimize this system in an effort to engineer and integrate robust subunits to fill large defects. PMID:26895780

Ultrahigh Performance C60 Nanorod Large Area Flexible Photoconductor Devices via Ultralow Organic and Inorganic Photodoping

PubMed Central

Saran, Rinku; Stolojan, Vlad; Curry, Richard J.

2014-01-01

One dimensional single-crystal nanorods of C60 possess unique optoelectronic properties including high electron mobility, high photosensitivity and an excellent electron accepting nature. In addition, their rapid large scale synthesis at room temperature makes these organic semiconducting nanorods highly attractive for advanced optoelectronic device applications. Here, we report low-cost large-area flexible photoconductor devices fabricated using C60 nanorods. We demonstrate that the photosensitivity of the C60 nanorods can be enhanced ~400-fold via an ultralow photodoping mechanism. The photodoped devices offer broadband UV-vis-NIR spectral tuneability, exhibit a detectivitiy >109 Jones, an external quantum efficiency of ~100%, a linear dynamic range of 80 dB, a rise time 60 µs and the ability to measure ac signals up to ~250 kHz. These figures of merit combined are among the highest reported for one dimensional organic and inorganic large-area planar photoconductors and are competitive with commercially available inorganic photoconductors and photoconductive cells. With the additional processing benefits providing compatibility with large-area flexible platforms, these devices represent significant advances and make C60 nanorods a promising candidate for advanced photodetector technologies. PMID:24853479

Development of SiC Large Tapered Crystal Growth

NASA Technical Reports Server (NTRS)

Neudeck, Phil

2011-01-01

Research Focus Area: Power Electronics, Temperature Tolerant Devices. Demonstrate initial feasibility of totally new "Large Tapered Crystal" (LTC) process for growing vastly improved large-diameter wide-band gap wafers. Addresses Targets: The goal of this research is to experimentally investigate and demonstrate feasibility of the key unproven LTC growth processes in SiC. Laser-assisted growth of long SiC fiber seeds. Radial epitaxial growth enlargement of seeds into large SiC boules. Uniqueness and Impacts open a new technology path to large-diameter SiC and GaN wafers with 1000-fold defect density improvement at 2-4 fold lower cost. Leapfrog improvement in wide band gap power device capability and cost.

Polyphase tertiary fold-and-thrust tectonics in the Belluno Dolomites: new mapping, kinematic analysis, and 3D modelling

NASA Astrophysics Data System (ADS)

Chistolini, Filippo; Bistacchi, Andrea; Massironi, Matteo; Consonni, Davide; Cortinovis, Silvia

2014-05-01

The Belluno Dolomites are comprised in the eastern sector of the Southern Alps, which corresponds to the fold-and-thrust belt at the retro-wedge of the Alpine collisional orogen. They are characterized by a complex and polyphase fold-and-thrust tectonics, highlighted by multiple thrust sheets and thrust-related folding. We have studied this tectonics in the Vajont area where a sequence of Jurassic, Cretaceous and Tertiary units have been involved in multiple deformations. The onset of contractional tectonics in this part of the Alps is constrained to be Tertiary (likely Post-Eocene) by structural relationships with the Erto Flysch, whilst in the Mesozoic tectonics was extensional. We have recognized two contractional deformation phases (D1 and D2 in the following), of which only the second was mentioned in previous studies of the area and attributed to the Miocene Neoalpine event. D1 and D2 are characterized by roughly top-to-WSW (possibly Dinaric) and top-to-S (Alpine) transport directions respectively, implying a 90° rotation of the regional-scale shortening axis, and resulting in complex thrust and fold interference and reactivation patterns. Geological mapping and detailed outcrop-scale kinematic analysis allowed us to characterize the kinematics and chronology of deformations. Particularly, relative chronology was unravelled thanks to (1) diagnostic fold interference patterns and (2) crosscutting relationships between thrust faults and thrust-related folds. A km-scale D1 syncline, filled with the Eocene Erto Flysch and "decapitated" by a D2 thrust fault, provides the best map-scale example of crosscutting relationships allowing to reconstruct the faulting history. Due to the strong competence contrast between Jurassic carbonates and Tertiary flysch, in this syncline spectacular duplexes were also developed during D2. In order to quantitatively characterize the complex interference pattern resulting from two orthogonal thrusting and folding events, we performed a dip-domain analysis that allowed to categorize the different fold limbs and reduce the uncertainty in the reconstruction of the fault network topology in map view. This enabled us to reconstruct a high-quality, low-uncertainty 3D structural and geological model, which unambiguously proves that deformations with a top-to-WSW Dinaric transport direction propagate farther to the west than previously supposed in this part of the Southern Alps. Our new structural reconstruction of the Vajont valley have also clarified the structural control on the 1963 catastrophic landslide (which caused over 2000 losses). Besides being a challenging natural laboratory for testing analysis and modelling methodologies to be used when reconstructing in 3D this kind of complex interference structures, the Vajont area also provides useful clues on the still-enigmatic structures in the frontal part of the Friuli-Venetian Southern Alps, buried in the Venetian Plain foredeep. These include active seismogenic thrust-faults and, at the same time, represent a growing interest for the oil industry.

Thermosensitivity of growth is determined by chaperone-mediated proteome reallocation

PubMed Central

Chen, Ke; Gao, Ye; Mih, Nathan; O’Brien, Edward J.; Yang, Laurence; Palsson, Bernhard O.

2017-01-01

Maintenance of a properly folded proteome is critical for bacterial survival at notably different growth temperatures. Understanding the molecular basis of thermoadaptation has progressed in two main directions, the sequence and structural basis of protein thermostability and the mechanistic principles of protein quality control assisted by chaperones. Yet we do not fully understand how structural integrity of the entire proteome is maintained under stress and how it affects cellular fitness. To address this challenge, we reconstruct a genome-scale protein-folding network for Escherichia coli and formulate a computational model, FoldME, that provides statistical descriptions of multiscale cellular response consistent with many datasets. FoldME simulations show (i) that the chaperones act as a system when they respond to unfolding stress rather than achieving efficient folding of any single component of the proteome, (ii) how the proteome is globally balanced between chaperones for folding and the complex machinery synthesizing the proteins in response to perturbation, (iii) how this balancing determines growth rate dependence on temperature and is achieved through nonspecific regulation, and (iv) how thermal instability of the individual protein affects the overall functional state of the proteome. Overall, these results expand our view of cellular regulation, from targeted specific control mechanisms to global regulation through a web of nonspecific competing interactions that modulate the optimal reallocation of cellular resources. The methodology developed in this study enables genome-scale integration of environment-dependent protein properties and a proteome-wide study of cellular stress responses. PMID:29073085

Outer Membrane Protein Folding and Topology from a Computational Transfer Free Energy Scale.

PubMed

Lin, Meishan; Gessmann, Dennis; Naveed, Hammad; Liang, Jie

2016-03-02

Knowledge of the transfer free energy of amino acids from aqueous solution to a lipid bilayer is essential for understanding membrane protein folding and for predicting membrane protein structure. Here we report a computational approach that can calculate the folding free energy of the transmembrane region of outer membrane β-barrel proteins (OMPs) by combining an empirical energy function with a reduced discrete state space model. We quantitatively analyzed the transfer free energies of 20 amino acid residues at the center of the lipid bilayer of OmpLA. Our results are in excellent agreement with the experimentally derived hydrophobicity scales. We further exhaustively calculated the transfer free energies of 20 amino acids at all positions in the TM region of OmpLA. We found that the asymmetry of the Gram-negative bacterial outer membrane as well as the TM residues of an OMP determine its functional fold in vivo. Our results suggest that the folding process of an OMP is driven by the lipid-facing residues in its hydrophobic core, and its NC-IN topology is determined by the differential stabilities of OMPs in the asymmetrical outer membrane. The folding free energy is further reduced by lipid A and assisted by general depth-dependent cooperativities that exist between polar and ionizable residues. Moreover, context-dependency of transfer free energies at specific positions in OmpLA predict regions important for protein function as well as structural anomalies. Our computational approach is fast, efficient and applicable to any OMP.

Velocity field measurements in oblique static divergent vocal fold models

NASA Astrophysics Data System (ADS)

Erath, Byron

2005-11-01

During normal phonation, the vocal fold cycle is characterized by the glottal opening transitioning from a convergent to a divergent passage and then closing before the cycle is repeated. Under ordinary phonatory conditions, both vocal folds, which form the glottal passage, move in phase with each other, creating a time-varying symmetric opening. However, abnormal pathological conditions, such as unilateral paralysis, and polyps, can result in geometrical asymmetries between the vocal folds throughout the phonatory cycle. This study investigates pulsatile flow fields through 7.5 times life-size vocal fold models with included divergence angles of 5 to 30 degrees, and obliquities between the vocal folds of up to 15 degrees. Flow conditions were scaled to match physiological parameters. Data were taken at the anterior posterior mid-plane using phase-averaged Particle Image Velocimetry (PIV). Viscous flow phenomena including the Coanda effect, flow separation points, and jet "flapping" were investigated. The results are compared to previously reported work of flow through symmetric divergent vocal fold models.

Investigating fold structures of 2D materials by quantitative transmission electron microscopy.

PubMed

Wang, Zhiwei; Zhang, Zengming; Liu, Wei; Wang, Zhong Lin

2017-04-01

We report an approach developed for deriving 3D structural information of 2D membrane folds based on the recently-established quantitative transmission electron microscopy (TEM) in combination with density functional theory (DFT) calculations. Systematic multislice simulations reveal that the membrane folding leads to sufficiently strong electron scattering which enables a precise determination of bending radius. The image contrast depends also on the folding angles of 2D materials due to the variation of projection potentials, which however exerts much smaller effect compared with the bending radii. DFT calculations show that folded edges are typically characteristic of (fractional) nanotubes with the same curvature retained after energy optimization. Owing to the exclusion of Stobbs factor issue, numerical simulations were directly used in comparison with the experimental measurements on an absolute contrast scale, which results in a successful determination of bending radius of folded monolayer MoS 2 films. The method should be applicable to characterizing all 2D membranes with 3D folding features. Copyright © 2017 Elsevier Ltd. All rights reserved.

Milankovitch Modulated Eocene Growth Strata From the Jaca Piggyback Basin, Spanish Pyrenees

NASA Astrophysics Data System (ADS)

Anastasio, D. J.; Hinnov, L. A.; Newton, M. L.; Kodama, K. P.

2005-12-01

New stratigraphic and rock magnetic data from the southern margin of the Jaca basin, Spanish Pyrenees, shows evidence of Eocene sedimentary cycles modulated by the climatic effects of Milankovitch orbital forcing. Tectonic processes simultaneously controlled larger-scale stratigraphic sequences and overall wedge-top basin development. Within the context of existing magnetostratigraphy, we described 1 km of marine basinal and prodeltaic rocks near Pico del Aguila, a large-scale synsedimentary fold, and collected samples every ~4krs for ~4myrs for lithologic and rock magnetic analysis. In magnetochrons C17r, C18n.1n, and C18n.1r (1.27myrs) anhysteretic remanent magnetization (ARM) variations occur with strong hierarchical bundling patterns suggestive of precession-scale cycles grouped into 100 kyr eccentricity cycles, and "super bundled" into 400 kyr eccentricity cycles. This pattern was exploited to construct an "eccentricity time scale" for the series producing a minimally tuned time series that is 1.3 myrs in duration; comparing well with the magnetochron calibration. Spectral analysis of this ARM time series shows that the 100-kyr tuning has aligned power into all of the principal orbital frequency bands: long eccentricity (1/(400 kyrs)), obliquity (1/(40.4 kyrs)), long precession (1/(24.4 kyrs)), and short precession (1/(20 kyrs)). Lithologic data, including bed thickness and grain size also shows high frequency periodicity we attribute to precessional forcing. ARM variations may result from climate modulated carbonate production or more likely, variable detrital inputs such as atmospheric dust (varying wind intensity or aridity) or watershed erosion (runoff variation) rather than diagenetic sources. The Milankovitch based chronology within the growth stratigraphy was then used to calculate deformation rates. Tilt rates of 9 degrees / myr for folding are comparable to other studies in which deformation was averaged over more time. We show that Milankovitch rhythms in growth strata can be used to develop novel high resolution, long-term deformation histories.

Native Contact Density and Nonnative Hydrophobic Effects in the Folding of Bacterial Immunity Proteins

PubMed Central

Chen, Tao; Chan, Hue Sun

2015-01-01

The bacterial colicin-immunity proteins Im7 and Im9 fold by different mechanisms. Experimentally, at pH 7.0 and 10°C, Im7 folds in a three-state manner via an intermediate but Im9 folding is two-state-like. Accordingly, Im7 exhibits a chevron rollover, whereas the chevron arm for Im9 folding is linear. Here we address the biophysical basis of their different behaviors by using native-centric models with and without additional transferrable, sequence-dependent energies. The Im7 chevron rollover is not captured by either a pure native-centric model or a model augmented by nonnative hydrophobic interactions with a uniform strength irrespective of residue type. By contrast, a more realistic nonnative interaction scheme that accounts for the difference in hydrophobicity among residues leads simultaneously to a chevron rollover for Im7 and an essentially linear folding chevron arm for Im9. Hydrophobic residues identified by published experiments to be involved in nonnative interactions during Im7 folding are found to participate in the strongest nonnative contacts in this model. Thus our observations support the experimental perspective that the Im7 folding intermediate is largely underpinned by nonnative interactions involving large hydrophobics. Our simulation suggests further that nonnative effects in Im7 are facilitated by a lower local native contact density relative to that of Im9. In a one-dimensional diffusion picture of Im7 folding with a coordinate- and stability-dependent diffusion coefficient, a significant chevron rollover is consistent with a diffusion coefficient that depends strongly on native stability at the conformational position of the folding intermediate. PMID:26016652

The ion-induced folding of the hammerhead ribozyme: core sequence changes that perturb folding into the active conformation.

PubMed Central

Bassi, G S; Murchie, A I; Lilley, D M

1996-01-01

The hammerhead ribozyme undergoes an ion-dependent folding process into the active conformation. We find that the folding can be blocked at specific stages by changes of sequence or functionality within the core. In the the absence of added metal ions, the global structure of the hammerhead is extended, with a large angle subtended between stems I and II. No core sequence changes appear to alter this geometry, consistent with an unstructured core under these conditions. Upon addition of low concentrations of magnesium ions, the hammerhead folds by an association of stems II and III, to include a large angle between them. This stage is inhibited or altered by mutations within the oligopurine sequence lying between stems II and III, and folding is completely prevented by an A14G mutation. Further increase in magnesium ion concentration brings about a second stage of folding in the natural sequence hammerhead, involving a reorientation of stem I, which rotates around into the same direction of stem II. Because this transition occurs over the same range of magnesium ion concentration over which the hammerhead ribozyme becomes active, it is likely that the final conformation is most closely related to the active form of the structure. Magnesium ion-dependent folding into this conformation is prevented by changes at G5, notably removal of the 2'-hydroxyl group and replacement of the base by cytidine. The ability to dissect the folding process by means of sequence changes suggests that two separate ion-dependent stages are involved in the folding of the hammerhead ribozyme into the active conformation. PMID:8752086

Impact on demersal fish of a large-scale and deep sand extraction site with ecosystem-based landscaped sandbars

NASA Astrophysics Data System (ADS)

de Jong, Maarten F.; Baptist, Martin J.; van Hal, Ralf; de Boois, Ingeborg J.; Lindeboom, Han J.; Hoekstra, Piet

2014-06-01

For the seaward harbour extension of the Port of Rotterdam in the Netherlands, approximately 220 million m3 sand was extracted between 2009 and 2013. In order to decrease the surface area of direct impact, the authorities permitted deep sand extraction, down to 20 m below the seabed. Biological and physical impacts of large-scale and deep sand extraction are still being investigated and largely unknown. For this reason, we investigated the colonization of demersal fish in a deep sand extraction site. Two sandbars were artificially created by selective dredging, copying naturally occurring meso-scale bedforms to increase habitat heterogeneity and increasing post-dredging benthic and demersal fish species richness and biomass. Significant differences in demersal fish species assemblages in the sand extraction site were associated with variables such as water depth, median grain size, fraction of very fine sand, biomass of white furrow shell (Abra alba) and time after the cessation of sand extraction. Large quantities of undigested crushed white furrow shell fragments were found in all stomachs and intestines of plaice (Pleuronectes platessa), indicating that it is an important prey item. One and two years after cessation, a significant 20-fold increase in demersal fish biomass was observed in deep parts of the extraction site. In the troughs of a landscaped sandbar however, a significant drop in biomass down to reference levels and a significant change in species assemblage was observed two years after cessation. The fish assemblage at the crests of the sandbars differed significantly from the troughs with tub gurnard (Chelidonichthys lucerna) being a Dufrêne-Legendre indicator species of the crests. This is a first indication of the applicability of landscaping techniques to induce heterogeneity of the seabed although it remains difficult to draw a strong conclusion due the lack of replication in the experiment. A new ecological equilibrium is not reached after 2 years since biotic and abiotic variables are still adapting. To understand the final impact of deep and large-scale sand extraction on demersal fish, we recommend monitoring for a longer period, at least for a period of six years or even longer.

Does laryngeal reinnervation or type I thyroplasty give better voice results for patients with unilateral vocal fold paralysis (VOCALIST): study protocol for a feasibility randomised controlled trial

PubMed Central

Blackshaw, Helen; Carding, Paul; Jepson, Marcus; Mat Baki, Marina; Ambler, Gareth; Schilder, Anne; Morris, Stephen; Degun, Aneeka; Yu, Rosamund; Husbands, Samantha; Knowles, Helen; Walton, Chloe; Karagama, Yakubu; Heathcote, Kate; Birchall, Martin

2017-01-01

Introduction A functioning voice is essential for normal human communication. A good voice requires two moving vocal folds; if one fold is paralysed (unilateral vocal fold paralysis (UVFP)) people suffer from a breathy, weak voice that tires easily and is unable to function normally. UVFP can also result in choking and breathlessness. Current treatment for adults with UVFP is speech therapy to stimulate recovery of vocal fold (VF) motion or function and/or injection of the paralysed VF with a material to move it into a more favourable position for the functioning VF to close against. When these therapies are unsuccessful, or only provide temporary relief, surgery is offered. Two available surgical techniques are: (1) surgical medialisation; placing an implant near the paralysed VF to move it to the middle (thyroplasty) and/or repositioning the cartilage (arytenoid adduction) or (2) restoring the nerve supply to the VF (laryngeal reinnervation). Currently there is limited evidence to determine which surgery should be offered to adults with UVFP. Methods and analysis A feasibility study to test the practicality of running a multicentre, randomised clinical trial of surgery for UVFP, including: (1) a qualitative study to understand the recruitment process and how it operates in clinical centres and (2) a small randomised trial of 30 participants recruited at 3 UK sites comparing non-selective laryngeal reinnervation to type I thyroplasty. Participants will be followed up for 12 months. The primary outcome focuses on recruitment and retention, with secondary outcomes covering voice, swallowing and quality of life. Ethics and dissemination Ethical approval was received from National Research Ethics Service—Committee Bromley (reference 11/LO/0583). In addition to dissemination of results through presentation and publication of peer-reviewed articles, results will be shared with key clinician and patient groups required to develop the future large-scale randomised controlled trial. Trial registration number ISRCTN90201732; 16 December 2015. PMID:28965097

Epithelial Folding Driven by Apical or Basal-Lateral Modulation: Geometric Features, Mechanical Inference, and Boundary Effects.

PubMed

Wen, Fu-Lai; Wang, Yu-Chiun; Shibata, Tatsuo

2017-06-20

During embryonic development, epithelial sheets fold into complex structures required for tissue and organ functions. Although substantial efforts have been devoted to identifying molecular mechanisms underlying epithelial folding, far less is understood about how forces deform individual cells to sculpt the overall sheet morphology. Here we describe a simple and general theoretical model for the autonomous folding of monolayered epithelial sheets. We show that active modulation of intracellular mechanics along the basal-lateral as well as the apical surfaces is capable of inducing fold formation in the absence of buckling instability. Apical modulation sculpts epithelia into shallow and V-shaped folds, whereas basal-lateral modulation generates deep and U-shaped folds. These characteristic tissue shapes remain unchanged when subject to mechanical perturbations from the surroundings, illustrating that the autonomous folding is robust against environmental variabilities. At the cellular scale, how cells change shape depends on their initial aspect ratios and the modulation mechanisms. Such cell deformation characteristics are verified via experimental measurements for a canonical folding process driven by apical modulation, indicating that our theory could be used to infer the underlying folding mechanisms based on experimental data. The mechanical principles revealed in our model could potentially guide future studies on epithelial folding in diverse systems. Copyright © 2017. Published by Elsevier Inc.

Improving Protein Fold Recognition by Deep Learning Networks.

PubMed

Jo, Taeho; Hou, Jie; Eickholt, Jesse; Cheng, Jianlin

2015-12-04

For accurate recognition of protein folds, a deep learning network method (DN-Fold) was developed to predict if a given query-template protein pair belongs to the same structural fold. The input used stemmed from the protein sequence and structural features extracted from the protein pair. We evaluated the performance of DN-Fold along with 18 different methods on Lindahl's benchmark dataset and on a large benchmark set extracted from SCOP 1.75 consisting of about one million protein pairs, at three different levels of fold recognition (i.e., protein family, superfamily, and fold) depending on the evolutionary distance between protein sequences. The correct recognition rate of ensembled DN-Fold for Top 1 predictions is 84.5%, 61.5%, and 33.6% and for Top 5 is 91.2%, 76.5%, and 60.7% at family, superfamily, and fold levels, respectively. We also evaluated the performance of single DN-Fold (DN-FoldS), which showed the comparable results at the level of family and superfamily, compared to ensemble DN-Fold. Finally, we extended the binary classification problem of fold recognition to real-value regression task, which also show a promising performance. DN-Fold is freely available through a web server at http://iris.rnet.missouri.edu/dnfold.

Programming curvature using origami tessellations

NASA Astrophysics Data System (ADS)

Dudte, Levi H.; Vouga, Etienne; Tachi, Tomohiro; Mahadevan, L.

2016-05-01

Origami describes rules for creating folded structures from patterns on a flat sheet, but does not prescribe how patterns can be designed to fit target shapes. Here, starting from the simplest periodic origami pattern that yields one-degree-of-freedom collapsible structures--we show that scale-independent elementary geometric constructions and constrained optimization algorithms can be used to determine spatially modulated patterns that yield approximations to given surfaces of constant or varying curvature. Paper models confirm the feasibility of our calculations. We also assess the difficulty of realizing these geometric structures by quantifying the energetic barrier that separates the metastable flat and folded states. Moreover, we characterize the trade-off between the accuracy to which the pattern conforms to the target surface, and the effort associated with creating finer folds. Our approach enables the tailoring of origami patterns to drape complex surfaces independent of absolute scale, as well as the quantification of the energetic and material cost of doing so.

Standardized laryngeal videostroboscopic rating: differences between untrained and trained male and female subjects, and effects of varying sound intensity, fundamental frequency, and age.

PubMed

Sulter, A M; Schutte, H K; Miller, D G

1996-06-01

To determine the influence of the factors gender, vocal training, sound intensity, pitch, and aging on vocal function, videolaryngostroboscopic images of 214 subjects, subdivided according to gender and status of vocal training, were evaluated by three judges with standardized rating scales, comprising aspects of laryngeal appearance (larynx/pharynx ratio; epiglottal shape; asymmetry arytenoid region; compensatory adjustments; thickness, width, length, and elasticity of vocal folds) and glottal functioning (amplitudes of excursion; duration, percentage, and type of vocal fold closure; phase differences; location of glottal chink). The video registrations were made while the subjects performed a set of phonatory tasks, comprising the utterance of the vowel /i/ at three levels of both fundamental frequency and sound intensity. Analysis of the rating scales showed generally sufficient agreement among judges. With the exception of more frequently observed complete closure and lateral phase differences of vocal fold excursions in trained subjects, no further differences were established between untrained and trained subjects. With an alpha level of p = 0.005, men differed from women with respect to laryngeal appearance (larynx/pharynx ratio, compensatory adjustments, and the presence of omega and deviant-shaped epiglottises), and their vocal folds were rated thicker in the vertical dimension, smaller in the lateral dimension, longer, and more tense, with smaller amplitudes of excursion during vibration. Glottal closure in male subjects was rated more complete, but briefer in duration. Significant effects of the factors pitch, sound intensity, and age on vocal fold appearance and glottal functioning were ascertained. Awareness of the influence of these factors, as well as the factor gender, on the rated scales is essential for an adequate evaluation of laryngostroboscopic images.

Functional assessment of the ex vivo vocal folds through biomechanical testing: A review

PubMed Central

Dion, Gregory R.; Jeswani, Seema; Roof, Scott; Fritz, Mark; Coelho, Paulo; Sobieraj, Michael; Amin, Milan R.; Branski, Ryan C.

2016-01-01

The human vocal folds are complex structures made up of distinct layers that vary in cellular and extracellular composition. The mechanical properties of vocal fold tissue are fundamental to the study of both the acoustics and biomechanics of voice production. To date, quantitative methods have been applied to characterize the vocal fold tissue in both normal and pathologic conditions. This review describes, summarizes, and discusses the most commonly employed methods for vocal fold biomechanical testing. Force-elongation, torsional parallel plate rheometry, simple-shear parallel plate rheometry, linear skin rheometry, and indentation are the most frequently employed biomechanical tests for vocal fold tissues and each provide material properties data that can be used to compare native tissue verses diseased for treated tissue. Force-elongation testing is clinically useful, as it allows for functional unit testing, while rheometry provides physiologically relevant shear data, and nanoindentation permits micrometer scale testing across different areas of the vocal fold as well as whole organ testing. Thoughtful selection of the testing technique during experimental design to evaluate a hypothesis is important to optimizing biomechanical testing of vocal fold tissues. PMID:27127075

Patterns of cetacean vaginal folds yield insights into functionality

PubMed Central

Orbach, Dara N.; Marshall, Christopher D.; Mesnick, Sarah L.; Würsig, Bernd

2017-01-01

Complex foldings of the vaginal wall are unique to some cetaceans and artiodactyls and are of unknown function(s). The patterns of vaginal length and cumulative vaginal fold length were assessed in relation to body length and to each other in a phylogenetic context to derive insights into functionality. The reproductive tracts of 59 female cetaceans (20 species, 6 families) were dissected. Phylogenetically-controlled reduced major axis regressions were used to establish a scaling trend for the female genitalia of cetaceans. An unparalleled level of vaginal diversity within a mammalian order was found. Vaginal folds varied in number and size across species, and vaginal fold length was positively allometric with body length. Vaginal length was not a significant predictor of vaginal fold length. Functional hypotheses regarding the role of vaginal folds and the potential selection pressures that could lead to evolution of these structures are discussed. Vaginal folds may present physical barriers, which obscure the pathway of seawater and/or sperm travelling through the vagina. This study contributes broad insights to the evolution of reproductive morphology and aquatic adaptations and lays the foundation for future functional morphology analyses. PMID:28362830

Surface response of blind thrust shown from high resolution topographic data and updated geochronology at Wheeler Ridge, CA

NASA Astrophysics Data System (ADS)

Kleber, E.; Arrowsmith, R.; DeVecchio, D. E.; Johnstone, S. A.; Rittenour, T. M.

2015-12-01

Wheeler Ridge is an asymmetric east-propagating anticline (10km axis, 330m relief) above a north-vergent blind thrust deforming Quaternary alluvial fan and shallow marine rocks at the northern front of the Transverse Ranges, San Joaquin Valley, CA. This area was a research foci in the 1990's when the soils, u-series soil carbonate dating, and subsurface structure of deformed strata identified from oil wells were used to create a kinematic model of deformation, and estimates of fault slip, uplift, and lateral propagation rates. A recent collection of light detection and ranging (lidar) topographic data and optically stimulated luminescence (OSL) data allow us to complete meter scale topographic analyses of the fluvial networks and hillslopes and correlate geomorphic response to tectonics. We interpret these results using a detailed morphological map and observe drainage network and hillslope process transitions both along and across the fold axis. With lidar topography, we extract common morphometrics (e.g., channel steepness-- ksn, eroded volume, hillslope relief) to illustrate how the landscape is responding to variations in uplift rate along the fold axis and show asymmetry of surface response on the forelimb and backlimb. The forelimb is dominated by large drainages with landslides initiating in the marine units at the core of the fold. Our topographic analysis shows that the stream channel indices values on the forelimb increase along the fold axis, away from the propagation tip. The backlimb drainages are dominantly long and linear with broad ridgelines. Using lidar and fieldwork, we see that uplifted backlimb surfaces preserve the deformed fan surface. The preliminary OSL results from alluvial fan units improve age control of previously defined surfaces, refining our understanding of the deposition and uplift of alluvial fan units on preserved on backlimb.

Tilting of the Puy de Dome by a forced fold

NASA Astrophysics Data System (ADS)

van Wyk de Vries, Benjamin; Petronis, Michael; Garza, Daniel

2017-04-01

The Puy de Dome, like the leaning tower of Pisa, has one side steeper than the other. Paleomagnetic data from 14 sites show a consistent horizontal-axis rotation of 15° from the expected 11 ka paleomagnetic pole position for the site location. Morphological data further support these data: the south west side of the dome is steep, rugged and scarred with landslides, and has a breccia apron only at the base made of mass flow deposits: this side has steepened and lost material. In contrast, the northeast side of the dome is smooth and less steep, and is mantled by breccia on the upper flanks: this side has become more stable. In addition, the north flank of the Puy de Dôme has a deep gully that extends down in line with a fault scarp of the summit graben of an uplifted area that trends across the Petit Puy de Dôme. This uplift has been interpreted as a forced fold that developed over a trachyte intrusion. Stratigraphic data further show that the fold formed after the Puy de Dôme was formed. We conclude that the volcano was deformed, faulted, then shed the south west flank's carapace as it was tilted by the bulge. Monogenetic volcanoes, like the Puy de Dôme display in miniature processes, such tilting, that could feasibly provoke large scale landsliding at much larger volcanic edifices. The collapses at Bezimyanny (Kamchatka) and Mt St Helens (Oregon), involved the forced folding deformation of the edifice by internal intrusions. However, we argue that, it is possible that sills are preferentially intruded at the margins of volcanic centres, and hence whole volcano tilting could be more common occurrence than previously recognised.

Structural Evolution of a Crustal Scale Tectonic Boundary in the 1 Ga Sveconorwegian Orogen, SW Sweden.

NASA Astrophysics Data System (ADS)

Pinan-Llamas, A.; Möller, C.; Andersson, J.

2016-12-01

We present new structural data to document Sveconorwegian deformational structures preserved in rocks of the Idefjorden Terrane (IT), the Eastern Segment (ES) and a formerly deep-seated tectonic boundary between them, the Mylonite Zone (MZ), in SW Sweden. We aim to integrate structural, petrologic and geochronological data to reconstruct a model for the Sveconorwegian deformation. The SE-vergent MZ is a crustal scale thrust that juxtaposed the allochtonous IT in the hanging wall against the eclogite-bearing ES in the footwall during the Sveconorwegian orogeny. In the research area, rocks of the IT are characterized by a roughly N-S striking tectonic banding that dips shallowly to the W and contains west or WNW-plunging stretching lineations. This gneissic banding is folded by asymmetric and overturned S- or SW-verging similar folds, which in highly strained areas become isoclinal and recumbent. In sections parallel to the lineation, most kinematic indicators are consistent with a top-down-to-the-west sense of shear, i.e. accommodating E-W extension. At the terrane boundary (MZ), ultramylonites and sheath folds are locally present. Immediately east of the MZ, rocks of the ES show a NW-SE to NE-SW striking tectonic banding (Sc) containing shallowly W- and SW-plunging stretching lineations. Sc locally preserves kinematic indicators and intrafolial folds (F1) that we relate to a first Sveconorwegian deformation phase D1. D1 fabrics were folded by asymmetric NE-SW to E-W trending F2 similar folds that are SE- to S-verging. In highly strained areas, these folds are isoclinal and recumbent. The main stretching lineation is sub-parallel to F2 fold axes. In sections subparallel to the lineation, kinematic indicators show a top-down-to-the-west or southwest sense of shear, including extensional shear bands that are overprinting F2 folds. Upright open F3 folds affect earlier fabrics. While D1 fabrics likely resulted from foreland-directed (east-vergent) thrusting that juxtaposed an eclogite-bearing terrane with eclogite-free units in the ES, D2 fabrics (shear-related folds and subsequent shear bands) may be related to E-W or NW-SE extensional or transtensional deformation after the main contractional phases of the orogeny. F3 folds might have resulted from accommodation during protracted E-W extension.

Limited fluid in carbonate-shale hosted thrust faults of the Rocky Mountain Fold-and-Thrust Belt (Sun River Canyon, Montana)

NASA Astrophysics Data System (ADS)

OBrien, V. J.; Kirschner, D. L.

2001-12-01

It is widely accepted that fluids play a fundamental role in the movement of thrust faults in foreland fold-and-thrust belts. We have begun a combined structure-geochemistry study of faults in the Rocky Mountain fold-and-thrust belt in order to provide more insight into the occurrence and role(s) of fluid in the deformation of thrust faults. We focus on faults exposed in the Sun River Canyon of Montana, an area that contains some of the best exposures of the Rocky Mountain fold-and-thrust belt in the U.S. Samples were collected from two well exposed thrusts in the Canyon -- the Diversion and French thrusts. Both faults have thrust Mississippian dolostones over Cretaceous shales. Displacement exceeds several kilometers. Numerous small-displacement, subsidiary faults characterize the deformation in the hanging wall carbonates. The footwall shales accommodated more penetrative deformation, resulting in well developed foliation and small-scale folds. Stable isotope data have been obtained from host rock samples and veins from these faults. The data delimit an arcuate trend in oxygen-carbon isotope space. Approximately 50 host rock carbonate samples from the hanging walls have carbon and oxygen isotope values ranging from +3 to 0 and 28 to 19 per mil, respectively. There is no apparent correlation between isotopic values and distance from thrust fault at either locality. Fifteen samples of fibrous slickensides on small-displacement faults in the hanging walls have similar carbon and lower oxygen isotope values (down to 16 per mil). And 15 veins that either post-date thrusting or are of indeterminate origin have carbon and oxygen isotope values down to -3 and12 per mil, respectively. The isotopic data collected during the initial stages of this project are similar to some results obtained several hundred kilometers north in the Front Ranges of the Canadian Rockies (Kirschner and Kennedy, JGR 2000) and in carbonate fold-thrust belts of the Swiss Helvetic Alps and Italian Apennines. These data are consistent with limited infiltration of fluid through fractures and minor faults into hanging walls of large-displacement thrust faults.

Deformation sequences of the Day Nui Con Voi metamorphic belt, northern Vietnam

NASA Astrophysics Data System (ADS)

Yeh, M. W.; Lee, T. Y.; Lo, C. H.; Chung, S. L.; Lan, C. Y.; Lee, J. C.; Lin, T. S.; Lin, Y. J.

2003-04-01

The correlation of structure, microstructure and metamorphic assemblages is of fundamental importance to the understanding of the complex tectonic history and kinematics of the Day Nui Con Voi (DNCV) metamorphic belt in Vietnam along the Ailao Shan-Red River (ASRR) shear zone as it provides constraints on the relative timing of the deformation, kinematics and metamorphism. High-grade metamorphic rocks of amphibolite faces showed consistent deformation sequences of three folding events followed by one brittle deformation through all four cross sections from Lao Cai to Viet Tri indicated the DNCV belt experienced similar deformation condition throughout its length. The first deformation event, D1, produced up-right folds (locally preserved) with sub-vertical, NE-SW striking axial planes with dextral sense of shear probably formed during the early phase of the lowermost Triassic Indosinian orogeny. Followed by this compressional event is a gravitational collapsing event, D2, which is the major deformation and metamorphic event characterized by kyanite grade metamorphism and large scale horizontal folds with NW-SE (320) striking sub-horizontal axial pane showing sinsistral sense of shear most likely formed during the Oligocene-Miocene SE extrusion of Indochina peninsula. The 3rd folding event, D3, is a post-metamorphism doming event with NW-SE (310) striking sub-vertical axial plane that folded/tilted the once sub-horizontal D2 axial planes into shallowly (<30 degrees) NE dipping on the NE limb, and SW dipping on the SW limb possibly due to left-lateral movement of the N-S trending Xian Shui He fault system in Mid-Miocene. The outward decreasing of the metamorphic grade from kyanite to garnet then biotite indicated the D3 occurred post metamorphism. Reactivation of the sub-horizontal D2 fold axial planes showed dextral sense of shear possibly due to Late Miocene-Pliocene right-lateral movement of the ASRR shear zone. This right lateral movement continuously deformed the DNCV with brittle fractures such as joints and normal faults (D4) striking NE-SW to E-W and NW-SE.

Sequence-dependent folding landscapes of adenine riboswitch aptamers.

PubMed

Lin, Jong-Chin; Hyeon, Changbong; Thirumalai, D

2014-04-14

Expression of a large fraction of genes in bacteria is controlled by riboswitches, which are found in the untranslated region of mRNA. Structurally riboswitches have a conserved aptamer domain to which a metabolite binds, resulting in a conformational change in the downstream expression platform. Prediction of the functions of riboswitches requires a quantitative description of the folding landscape so that the barriers and time scales for the conformational change in the switching region in the aptamer can be estimated. Using a combination of all atom molecular dynamics (MD) and coarse-grained model simulations we studied the response of adenine (A) binding add and pbuE A-riboswitches to mechanical force. The two riboswitches contain a structurally similar three-way junction formed by three paired helices, P1, P2, and P3, but carry out different functions. Using pulling simulations, with structures generated in MD simulations, we show that after P1 rips the dominant unfolding pathway in the add A-riboswitch is the rupture of P2 followed by unraveling of P3. In the pbuE A-riboswitch, after P1 unfolds P3 ruptures ahead of P2. The order of unfolding of the helices, which is in accord with single molecule pulling experiments, is determined by the relative stabilities of the individual helices. Our results show that the stability of isolated helices determines the order of assembly and response to force in these non-coding regions. We use the simulated free energy profile for the pbuE A-riboswitch to estimate the time scale for allosteric switching, which shows that this riboswitch is under kinetic control lending additional support to the conclusion based on single molecule pulling experiments. A consequence of the stability hypothesis is that a single point mutation (U28C) in the P2 helix of the add A-riboswitch, which increases the stability of P2, would make the folding landscapes of the two riboswitches similar. This prediction can be tested in single molecule pulling experiments.

Paleoseismologic evidence for large-magnitude (Mw 7.5-8.0) earthquakes on the Ventura blind thrust fault: Implications for multifault ruptures in the Transverse Ranges of southern California

USGS Publications Warehouse

McAuliffe, Lee J.; Dolan, James F.; Rhodes, Edward J.; Hubbard, Judith; Shaw, John H.; Pratt, Thomas L.

2015-01-01

Detailed analysis of continuously cored boreholes and cone penetrometer tests (CPTs), high-resolution seismic-reflection data, and luminescence and 14C dates from Holocene strata folded above the tip of the Ventura blind thrust fault constrain the ages and displacements of the two (or more) most recent earthquakes. These two earthquakes, which are identified by a prominent surface fold scarp and a stratigraphic sequence that thickens across an older buried fold scarp, occurred before the 235-yr-long historic era and after 805 ± 75 yr ago (most recent folding event[s]) and between 4065 and 4665 yr ago (previous folding event[s]). Minimum uplift in these two scarp-forming events was ∼6 m for the most recent earthquake(s) and ∼5.2 m for the previous event(s). Large uplifts such as these typically occur in large-magnitude earthquakes in the range of Mw7.5–8.0. Any such events along the Ventura fault would likely involve rupture of other Transverse Ranges faults to the east and west and/or rupture downward onto the deep, low-angle décollements that underlie these faults. The proximity of this large reverse-fault system to major population centers, including the greater Los Angeles region, and the potential for tsunami generation during ruptures extending offshore along the western parts of the system highlight the importance of understanding the complex behavior of these faults for probabilistic seismic hazard assessment.

A Method for Estimating 2D Horizontal Shortening at Wrinkle Ridges from Remote Sensing Data: Results from the Yakima Fold Belt (Columbia Plateau)

NASA Astrophysics Data System (ADS)

Mege, D.

1999-03-01

Field data and length/displacement scaling laws applied to the Yakima fold belt on the Columbia Plateau are used to demonstrate a method for estimating surface shortening of wrinkle ridge areas. Application to martian wrinkle ridges is given in another abstract.

Publications - MP 141 | Alaska Division of Geological & Geophysical Surveys

Science.gov Websites

DGGS MP 141 Publication Details Title: Quaternary faults and folds in Alaska: A digital database Combellick, R.A., 2012, Quaternary faults and folds in Alaska: A digital database, in Koehler, R.D Quaternary faults, scale 1:3,700,000 (63.0 M) Digital Geospatial Data Digital Geospatial Data Quaternary

FE Modelling of the Fluid-Structure-Acoustic Interaction for the Vocal Folds Self-Oscillation

NASA Astrophysics Data System (ADS)

Švancara, Pavel; Horáček, J.; Hrůza, V.

The flow induced self-oscillation of the human vocal folds in interaction with acoustic processes in the simplified vocal tract model was explored by three-dimensional (3D) finite element (FE) model. Developed FE model includes vocal folds pretension before phonation, large deformations of the vocal fold tissue, vocal folds contact, fluid-structure interaction, morphing the fluid mesh according the vocal folds motion (Arbitrary Lagrangian-Eulerian approach), unsteady viscous compressible airflow described by the Navier-Stokes equations and airflow separation during the glottis closure. Iterative partitioned approach is used for modelling the fluid-structure interaction. Computed results prove that the developed model can be used for simulation of the vocal folds self-oscillation and resulting acoustic waves. The developed model enables to numerically simulate an influence of some pathological changes in the vocal fold tissue on the voice production.

l-arginine modulates inflammation and muscle regulatory genes after a single session of resistance exercise in rats.

PubMed

Morais, S R L; Brito, V G B; Mello, W G; Oliveira, S H P

2018-02-01

We investigated the skeletal muscle adaptation to l-arginine supplementation prior to a single session of resistance exercise (RE) during the early phase of muscle repair. Wistar rats were randomly assigned into non-exercised (Control), RE plus vehicle (RE); RE plus l-arginine (RE+L-arg) and RE plus aminoguanidine (RE+AG) groups. Animals received four doses of either vehicle (0.9% NaCl), l-arg (1 g/b.w.), or AG (iNOS inhibitor) (50 mg/b.w.). The animals performed a single RE session until the concentric failure (ladder climbing; 80% overload) and the skeletal muscles were harvested at 0, 8, 24, and 48 hours post-RE. The RE resulted in increased neutrophil infiltrate (24 hours post-RE) (3621 vs 11852; P<.0001) associated with enhanced TNF-α (819.49 vs 357.02; P<.005) and IL-6 (3.84 vs 1.08; P<.0001). Prior, l-arginine supplementation attenuates neutrophil infiltration (5622; P<.0001), and also TNF-α (506.01; P<.05) and IL-6 (2.51, P<.05) levels. AG pretreatment mediated an inhibition of iNOS levels similar to levels found in RE group. RE animals displayed increased of atrogin-1 (1.9 fold) and MuRF-1 (3.2 fold) mRNA levels, reversed by l-arg supplementation [atrogin-1 (0.6 fold; P<.001); MuRF-1 (0.8-fold; P<.001)] at 24 hours post-RE. MyoD up-regulated levels were restricted to l-arg treated animals at 24 hours (2.8 vs 1.5 fold; P<.005) and 48 hours post-RE (2.4 vs 1.1 fold; P<.001). AG pretreatment reversed these processes at 24 hours [atrogin-1 (2.1 fold; P<.0001); MuRF-1 (2.5 fold; P<.0001); MyoD (1.4 fold)]. l-arginine supplementation seems to attenuate the resolution of RE-induced muscle inflammation and up-regulates MyoD expression during the early phase of muscle repair. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

GPR Imaging of Fault Related Folds in a Gold-Bearing Metasedimentary Sequence, Carolina Terrane, Southern Appalachian Mountains

NASA Astrophysics Data System (ADS)

Diemer, J. A.; Bobyarchick, A. R.

2015-12-01

The Carolina terrane comprises Ediacaran to earliest Paleozoic mixed magmatic and sedimentary assemblages in the central and eastern Piedmont of the Southern Appalachian Mountains. The terrane was primarily deformed during the Late Ordovician Cherokee orogeny, that reached greenschist facies metamorphism. The Albemarle arc, a younger component of the Carolina terrane, contains volcanogenic metasedimentary rocks with intercalated mainly rhyolitic volcanic rocks. Regional inclined to overturned folds with axial planar cleavage verge southeast. At mesoscopic scales (exposures of a few square meters), folds sympathetic with regional folds are attenuated or truncated by ductile shear zones or contractional faults. Shear and fault zones are most abundant near highly silicified strataform zones in metagraywacke of the Tillery Formation; these zones are also auriferous. GPR profiles were collected across strike of two silicified, gold-bearing zones and enclosing metagraywacke to characterize the scale and extent of folding in the vicinity of ore horizons. Several GSSI SIR-3000 / 100 MHz monostatic GPR profiles were collected in profiles up to 260 meters long. In pre-migration lines processed for time zero and background removal, several clusters of shallow, rolling sigmoidal reflectors appeared separated by sets of parallel, northwest-dipping reflective discontinuities. These features are inferred to be reverse faults carrying contractional folds. After migration with an average velocity of 0.105 m/ns, vertical heights of the inferred folds became attenuated but not removed, and contractional fault reflections remained prominent. After migration, a highly convex-up cluster of reflections initially assumed to be a fold culmination resolved to an elliptical patch of high amplitudes. The patch is likely an undisclosed shaft or covered trench left by earlier gold prospecting. In this survey, useful detail appeared to a depth of 7.5 meters, and only a few gently inclined, laterally extensive reflectors are present inside the noise blanket. Also, convex-up planar reflectors greater than about 8 meters deep and tens of meters long suggest fold culminations much longer in wavelength than the shallow imaged folds. For these metasedimentary rocks GPR provides a valuable tool for imaging sub-surface structure.

Small-scale disturbances in the stratigraphy of the NEEM ice core: observations and numerical model simulations

NASA Astrophysics Data System (ADS)

Jansen, D.; Llorens, M.-G.; Westhoff, J.; Steinbach, F.; Kipfstuhl, S.; Bons, P. D.; Griera, A.; Weikusat, I.

2016-02-01

Disturbances on the centimetre scale in the stratigraphy of the North Greenland Eemian Ice Drilling (NEEM) ice core (North Greenland) can be mapped by an optical line scanner as long as the ice has visual layering, such as, for example, cloudy bands. Different focal depths allow, to a certain extent, a three-dimensional view of the structures. In this study we present a detailed analysis of the visible folds, discuss their characteristics and frequency, and present examples of typical fold structures. We also analyse the structures with regard to the deformation boundary conditions under which they formed. The structures evolve from gentle waves at about 1500 m to overturned z folds with increasing depth. Occasionally, the folding causes significant thickening of layers. Their similar fold shape indicates that they are passive features and are probably not initiated by rheology differences between alternating layers. Layering is heavily disturbed and tracing of single layers is no longer possible below a depth of 2160 m. C axes orientation distributions for the corresponding core sections were analysed, where available, in addition to visual stratigraphy. The data show axial-plane parallel strings of grains with c axis orientations that deviate from that of the matrix, which shows a single maximum fabric at the depth where the folding occurs. Numerical modelling of crystal viscoplastic deformation and dynamic recrystallisation was used to improve the understanding of the formation of the observed structures during deformation. The modelling reproduces the development of bands of grains with a tilted-lattice orientation relative to the single maximum fabric of the matrix, and also the associated local deformation. We conclude from these results that the observed folding can be explained by formation of these tilted-lattice bands.

Spatial cognition and science achievement: The contribution of intrinsic and extrinsic spatial skills from 7 to 11 years.

PubMed

Hodgkiss, Alex; Gilligan, Katie A; Tolmie, Andrew K; Thomas, Michael S C; Farran, Emily K

2018-01-22

Prior longitudinal and correlational research with adults and adolescents indicates that spatial ability is a predictor of science learning and achievement. However, there is little research to date with primary-school aged children that addresses this relationship. Understanding this association has the potential to inform curriculum design and support the development of early interventions. This study examined the relationship between primary-school children's spatial skills and their science achievement. Children aged 7-11 years (N = 123) completed a battery of five spatial tasks, based on a model of spatial ability in which skills fall along two dimensions: intrinsic-extrinsic; static-dynamic. Participants also completed a curriculum-based science assessment. Controlling for verbal ability and age, mental folding (intrinsic-dynamic spatial ability), and spatial scaling (extrinsic-static spatial ability) each emerged as unique predictors of overall science scores, with mental folding a stronger predictor than spatial scaling. These spatial skills combined accounted for 8% of the variance in science scores. When considered by scientific discipline, mental folding uniquely predicted both physics and biology scores, and spatial scaling accounted for additional variance in biology and variance in chemistry scores. The children's embedded figures task (intrinsic-static spatial ability) only accounted for variance in chemistry scores. The patterns of association were consistent across the age range. Spatial skills, particularly mental folding, spatial scaling, and disembedding, are predictive of 7- to 11-year-olds' science achievement. These skills make a similar contribution to performance for each age group. © 2018 The Authors. British Journal of Education Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.

SeqRate: sequence-based protein folding type classification and rates prediction

PubMed Central

2010-01-01

Background Protein folding rate is an important property of a protein. Predicting protein folding rate is useful for understanding protein folding process and guiding protein design. Most previous methods of predicting protein folding rate require the tertiary structure of a protein as an input. And most methods do not distinguish the different kinetic nature (two-state folding or multi-state folding) of the proteins. Here we developed a method, SeqRate, to predict both protein folding kinetic type (two-state versus multi-state) and real-value folding rate using sequence length, amino acid composition, contact order, contact number, and secondary structure information predicted from only protein sequence with support vector machines. Results We systematically studied the contributions of individual features to folding rate prediction. On a standard benchmark dataset, the accuracy of folding kinetic type classification is 80%. The Pearson correlation coefficient and the mean absolute difference between predicted and experimental folding rates (sec-1) in the base-10 logarithmic scale are 0.81 and 0.79 for two-state protein folders, and 0.80 and 0.68 for three-state protein folders. SeqRate is the first sequence-based method for protein folding type classification and its accuracy of fold rate prediction is improved over previous sequence-based methods. Its performance can be further enhanced with additional information, such as structure-based geometric contacts, as inputs. Conclusions Both the web server and software of predicting folding rate are publicly available at http://casp.rnet.missouri.edu/fold_rate/index.html. PMID:20438647

High-rotational symmetry lattices fabricated by moiré nanolithography.

PubMed

Lubin, Steven M; Zhou, Wei; Hryn, Alexander J; Huntington, Mark D; Odom, Teri W

2012-09-12

This paper describes a new nanofabrication method, moiré nanolithography, that can fabricate subwavelength lattices with high-rotational symmetries. By exposing elastomeric photomasks sequentially at multiple offset angles, we created arrays with rotational symmetries as high as 36-fold, which is three times higher than quasiperiodic lattices (≤12-fold) and six times higher than two-dimensional periodic lattices (≤6-fold). Because these moiré nanopatterns can be generated over wafer-scale areas, they are promising for a range of photonic applications, especially those that require broadband, omnidirectional absorption of visible light.

Peppytides: Interactive Models of Polypeptide Chains

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

Zuckermann, Ron; Chakraborty, Promita; Derisi, Joe

2014-01-21

Peppytides are scaled, 3D-printed models of polypeptide chains that can be folded into accurate protein structures. Designed and created by Berkeley Lab Researcher, Promita Chakraborty, and Berkeley Lab Senior Scientist, Dr. Ron Zuckermann, Peppytides are accurate physical models of polypeptide chains that anyone can interact with and fold intro various protein structures - proving to be a great educational tool, resulting in a deeper understanding of these fascinating structures and how they function. Build your own Peppytide model and learn about how nature's machines fold into their intricate architectures!

Optimization of Training Sets For Neural-Net Processing of Characteristic Patterns From Vibrating Solids

NASA Technical Reports Server (NTRS)

Decker, Arthur J. (Inventor)

2006-01-01

An artificial neural network is disclosed that processes holography generated characteristic pattern of vibrating structures along with finite-element models. The present invention provides for a folding operation for conditioning training sets for optimally training forward-neural networks to process characteristic fringe pattern. The folding pattern increases the sensitivity of the feed-forward network for detecting changes in the characteristic pattern The folding routine manipulates input pixels so as to be scaled according to the location in an intensity range rather than the position in the characteristic pattern.

Peppytides: Interactive Models of Polypeptide Chains

ScienceCinema

Zuckermann, Ron; Chakraborty, Promita; Derisi, Joe

2018-06-08

Peppytides are scaled, 3D-printed models of polypeptide chains that can be folded into accurate protein structures. Designed and created by Berkeley Lab Researcher, Promita Chakraborty, and Berkeley Lab Senior Scientist, Dr. Ron Zuckermann, Peppytides are accurate physical models of polypeptide chains that anyone can interact with and fold intro various protein structures - proving to be a great educational tool, resulting in a deeper understanding of these fascinating structures and how they function. Build your own Peppytide model and learn about how nature's machines fold into their intricate architectures!

Can Advances in Science and Technology Prevent Global Warming? A Critical Review of Limitations and Challenges

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

Huesemann, Michael H.

The most stringent emission scenarios published by the Intergovernmental Panel on Climate Change (IPCC) would result in the stabilization of atmospheric carbon dioxide (CO2) at concentrations of approximately 550 ppm which would produce a global temperature increase of at least 2 C by 2100. Given the large uncertainties regarding the potential risks associated with this degree of global warming, it would be more prudent to stabilize atmospheric CO2 concentrations at or below current levels which, in turn, would require a greater than 20-fold reduction (i.e., ?95%) in per capita carbon emissions in industrialized nations within the next 50 to 100more » years. Using the Kaya equation as a conceptual framework, this paper examines whether CO2 mitigation approaches such as energy efficiency improvements, carbon sequestration, and the development of carbon-free energy sources would be sufficient to bring about the required reduction in per capita carbon emissions without creating unforeseen negative impacts elsewhere. In terms of energy efficiency, large improvements (?5-fold) are in principle possible given aggressive investments in R&D and if market imperfections such as corporate subsidies are removed. However, energy efficiency improvements per se will not result in a reduction in carbon emissions if, as predicted by the IPCC, the size of the global economy has expanded 12-26 fold by 2100. Terrestrial carbon sequestration via reforestation and improved agricultural soil management has many environmental advantages but has only limited CO2 mitigation potential because the global terrestrial carbon sink (ca. 200 Gt C) is small relative to the size of fossil fuel deposits (?4000 Gt C). By contrast, very large amounts of CO2 can potentially be removed from the atmosphere via sequestration in geologic formations and oceans, but carbon storage is not permanent and is likely to create many unpredictable environmental consequences. Renewable solar energy can in theory provide large amounts of carbon-free power. However, biomass and hydroelectric energy can only be marginally expanded and large-scale solar energy installations (i.e., wind, photovoltaics, and direct thermal) are likely to have significant negative environmental impacts. Expansion of nuclear energy is highly unlikely due to concerns over reactor safety, radioactive waste management, weapons proliferation, and cost. In view of the serious limitations and liabilities of many proposed CO2 mitigation approaches it appears that there remain only few no-regrets options such as drastic energy efficiency improvements, extensive terrestrial carbon sequestration, and cautious expansion of renewable energy generation. These promising CO2 mitigation technologies have the potential to bring about the required 20-fold reduction in per capita carbon emission only if population and economic growth are halted without delay. Thus, addressing the problem of global warming requires not only technological research and development but also a reexamination of core values that mistakenly equate material consumption and economic growth to happiness and well-being.« less

Complex fold and thrust belt structural styles: Examples from the Greater Juha area of the Papuan Fold and Thrust Belt, Papua New Guinea

NASA Astrophysics Data System (ADS)

Mahoney, Luke; Hill, Kevin; McLaren, Sandra; Hanani, Amanda

2017-07-01

The remote and inhospitable Papuan Fold Belt in Papua New Guinea is one of the youngest yet least well-documented fold and thrust belts on Earth. Within the frontal Greater Juha area we have carried out >100 km of geological traverses and associated analyses that have added significantly to the contemporary geological and geophysical dataset. Our structural analysis provides evidence of major inversion, detachment and triangle zone faults within the uplifted Eastern Muller Ranges. We have used the dataset to develop a quasi-3D model for the Greater Juha area, with associated cross-sections revealing that the exposed Cenozoic Darai Limestone is well-constrained with very low shortening of 12.6-21.4% yet structures are elevated up to 7 km above regional. We suggest the inversion of pre-existing rift architecture is the primary influence on the evolution of the area and that structures link to the surface via triangle zones and detachment faults within the incompetent Mesozoic passive-margin sedimentary sequence underlying competent Darai Limestone. Arc-normal oriented structures, dominantly oblique dextral, up-to-the-southeast, are pervasive across a range of scales and are here interpreted to relate at depth to weakened pre-existing basement cross-structures. It is proposed that Palaeozoic basement fabric controlled the structural framework of the basin during Early Mesozoic rifting forming regional-scale accommodation zones and related local-scale transfer structures that are now expressed as regional-scale arc-normal lineaments and local-scale arc-normal structures, respectively. Transfer structures, including complexly breached relay ramps, utilise northeast-southwest striking weaknesses associated with the basement fabric, as a mechanism for accommodating displacement along major northwest-southeast striking normal faults. These structures have subsequently been inverted to form arc-normal oriented zones of tear faulting that accommodate laterally variable displacement along inversion faults and connected thrust structures.

Effects of Magnetic and Kinetic Helicities on the Growth of Magnetic Fields in Laminar and Turbulent Flows by Helical Fourier Decomposition

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

Linkmann, Moritz; Sahoo, Ganapati; Biferale, Luca

We present a numerical and analytical study of incompressible homogeneous conducting fluids using a helical Fourier representation. We analytically study both small- and large-scale dynamo properties, as well as the inverse cascade of magnetic helicity, in the most general minimal subset of interacting velocity and magnetic fields on a closed Fourier triad. We mainly focus on the dependency of magnetic field growth as a function of the distribution of kinetic and magnetic helicities among the three interacting wavenumbers. By combining direct numerical simulations of the full magnetohydrodynamics equations with the helical Fourier decomposition, we numerically confirm that in the kinematicmore » dynamo regime the system develops a large-scale magnetic helicity with opposite sign compared to the small-scale kinetic helicity, a sort of triad-by-triad α -effect in Fourier space. Concerning the small-scale perturbations, we predict theoretically and confirm numerically that the largest instability is achived for the magnetic component with the same helicity of the flow, in agreement with the Stretch–Twist–Fold mechanism. Vice versa, in the presence of Lorentz feedback on the velocity, we find that the inverse cascade of magnetic helicity is mostly local if magnetic and kinetic helicities have opposite signs, while it is more nonlocal and more intense if they have the same sign, as predicted by the analytical approach. Our analytical and numerical results further demonstrate the potential of the helical Fourier decomposition to elucidate the entangled dynamics of magnetic and kinetic helicities both in fully developed turbulence and in laminar flows.« less

Differential gene expression in human abdominal aortic aneurysm and aortic occlusive disease

PubMed Central

Moran, Corey S.; Schreurs, Charlotte; Lindeman, Jan H. N.; Walker, Philip J.; Nataatmadja, Maria; West, Malcolm; Holdt, Lesca M.; Hinterseher, Irene; Pilarsky, Christian; Golledge, Jonathan

2015-01-01

Abdominal aortic aneurysm (AAA) and aortic occlusive disease (AOD) represent common causes of morbidity and mortality in elderly populations which were previously believed to have common aetiologies. The aim of this study was to assess the gene expression in human AAA and AOD. We performed microarrays using aortic specimen obtained from 20 patients with small AAAs (≤ 55mm), 29 patients with large AAAs (> 55mm), 9 AOD patients, and 10 control aortic specimens obtained from organ donors. Some differentially expressed genes were validated by quantitative-PCR (qRT-PCR)/immunohistochemistry. We identified 840 and 1,014 differentially expressed genes in small and large AAAs, respectively. Immune-related pathways including cytokine-cytokine receptor interaction and T-cell-receptor signalling were upregulated in both small and large AAAs. Examples of validated genes included CTLA4 (2.01-fold upregulated in small AAA, P = 0.002), NKTR (2.37-and 2.66-fold upregulated in small and large AAA with P = 0.041 and P = 0.015, respectively), and CD8A (2.57-fold upregulated in large AAA, P = 0.004). 1,765 differentially expressed genes were identified in AOD. Pathways upregulated in AOD included metabolic and oxidative phosphorylation categories. The UCP2 gene was downregulated in AOD (3.73-fold downregulated, validated P = 0.017). In conclusion, the AAA and AOD transcriptomes were very different suggesting that AAA and AOD have distinct pathogenic mechanisms. PMID:25944698

ITO-MgF2 Film Development for PowerSphere Polymer Surface Protection

NASA Technical Reports Server (NTRS)

Hambourger, Paul D.; Kerslake, Thomas W.; Waters, Deborah L.

2004-01-01

Multi-kilogram class microsatellites with a PowerSphere electric power system are attractive for fulfilling a variety of potential NASA missions. However, PowerSphere polymer surfaces must be coated with a film that has suitable electrical sheet resistivity for electrostatic discharge control, be resistant to atomic oxygen attack, be transparent to ultraviolet light for composite structure curing and resist ultraviolet light induced darkening for efficient photovoltaic cell operation. In addition, the film must be tolerant of polymer layer folding associated with launch stowage of PowerSphere inflatable structures. An excellent film material candidate to meet these requirements is co-sputtered, indium oxide (In2O3) - tin oxide (SnO2), known as 'ITO', and magnesium fluoride (MgF2). While basic ITO-MgF2 film properties have been the subject of research over the last decade, further research is required in the areas of film durability for space-inflatable applications and precise film property control for large scale commercial production. In this paper, the authors present film durability results for a folded polymer substrate and film resistance to vacuum UV darkening. The authors discuss methods and results in the area of film sheet resistivity measurement and active control, particularly dual-channel, plasma emission line measurement of ITO and MgF2 plasma sources. ITO-MgF2 film polymer coupon preparation is described as well as film deposition equipment, procedures and film characterization. Durability testing methods are also described. The pre- and post-test condition of the films is assessed microscopically and electrically. Results show that an approx. 500A ITO-18vol% MgF2 film is a promising candidate to protect PowerSphere polymer surfaces for Earth orbit missions. Preliminary data also indicate that in situ film measurement methods are promising for active film resistivity control in future large scale production. Future film research plans are also discussed.

Titer improvement of iso-migrastatin in selected heterologous Streptomyces hosts and related analysis of mRNA expression by quantitative RT–PCR

PubMed Central

Yang, Dong; Zhu, Xiangcheng; Wu, Xueyun; Feng, Zhiyang; Huang, Lei; Shen, Ben; Xu, Zhinan

2011-01-01

iso-Migrastatin (iso-MGS) has been actively pursued recently as an outstanding candidate of antimetastasis agents. Having characterized the iso-MGS biosynthetic gene cluster from its native producer Streptomyces platensis NRRL 18993, we have recently succeeded in producing iso-MGS in five selected heterologous Streptomyces hosts, albeit the low titers failed to meet expectations and cast doubt on the utility of this novel technique for large-scale production. To further explore and capitalize on the production capacity of these hosts, a thorough investigation of these five engineered strains with three fermentation media for iso-MGS production was undertaken. Streptomyces albus J1074 and Streptomyces lividans K4-114 were found to be preferred heterologous hosts, and subsequent analysis of carbon and nitrogen sources revealed that sucrose and yeast extract were ideal for iso-MGS production. After the initial optimization, the titers of iso-MGS in all five hosts were considerably improved by 3–18-fold in the optimized R2YE medium. Furthermore, the iso-MGS titer of S. albus J1074 (pBS11001) was significantly improved to 186.7 mg/L by a hybrid medium strategy. Addition of NaHCO3 to the latter finally afforded an optimized iso-MGS titer of 213.8 mg/L, about 5-fold higher than the originally reported system. With S. albus J1074 (pBS11001) as a model host, the expression of iso-MGS gene cluster in four different media was systematically studied via the quantitative RT–PCR technology. The resultant comparison revealed the correlation of gene expression and iso-MGS production for the first time; synchronous expression of the whole gene cluster was crucial for optimal iso-MGS production. These results reveal new insights into the iso-MGS biosynthetic machinery in heterologous hosts and provide the primary data to realize large-scale production of iso-MGS for further preclinical studies. PMID:21132287

Deposits of Large-scale Mass Movements in the Sediments of Hallstätter See (Austria) - Recurrent Natural Hazards at a UNESCO World Cultural Heritage Site

NASA Astrophysics Data System (ADS)

Lauterbach, S.; Strasser, M.; Tjallingii, R.; Kowarik, K.; Reschreiter, H.; Spatl, C.; Brauer, A.

2017-12-01

The cultural importance of underground salt mining in Hallstatt (Austria), which is documented since the Middle Bronze Age, has been recognized already 20 years ago by assigning the status of a UNESCO World Cultural Heritage Site to the Hallstatt area, particularly because of the wealth of archaeological artefacts from the Early Iron Age. Local mining activity is well documented for prehistoric times and known to have been repeatedly affected by large-scale mass movements, for example at the end of the Bronze Age and during the Late Iron Age. In contrast, evidence of mining activity between the 5th and late 13th century AD is scarce, which could be related to socio-economic changes but also to continued mass movement activity, possibly biasing the archaeological record. Within the present study, a 15.63-m-long 14C-dated sediment core from Hallstätter See has been investigated with respect to the deposits of large-scale mass movements. Most of the lake sediment sequence consists of cm- to sub-mm-scale laminated carbonate mud with frequently intercalated small-scale turbidites, reflecting seasonally variable detrital input from the tributaries, but two major event layers clearly stand out. The upper one comprises a 2.45-m-thick basal mass transport deposit (containing folded laminated sediments, homogenized sediments with liquefaction structures, and coarse gravel) and an overlying 1.45-m-thick co-genetic turbidite. From the lower event layer only the topmost part of the turbiditic sequence with a (minimum) thickness of 1.49 m was recovered. Based on their sedimentological characteristics, both event layers are interpreted as the subaqueous continuation of large-scale mass movements, which occurred at ca. 1050 and 2300 cal. years BP and possibly originated from the rock walls along the western lake shore where also the salt mining area is located. This indicates that mass movement activity not only threatened prehistoric salt mining, but occurred also repeatedly during the Common Era, possibly explaining the lack of archaeological evidence of mining activity between the 5th and late 13th century AD. However, a direct spatial and temporal relationship between documented mass movements in the mining area and those recorded in the lake sediments cannot be proven at present and requires further investigations.

Replica exchange molecular dynamics simulation of structure variation from α/4β-fold to 3α-fold protein.

PubMed

Lazim, Raudah; Mei, Ye; Zhang, Dawei

2012-03-01

Replica exchange molecular dynamics (REMD) simulation provides an efficient conformational sampling tool for the study of protein folding. In this study, we explore the mechanism directing the structure variation from α/4β-fold protein to 3α-fold protein after mutation by conducting REMD simulation on 42 replicas with temperatures ranging from 270 K to 710 K. The simulation began from a protein possessing the primary structure of GA88 but the tertiary structure of GB88, two G proteins with "high sequence identity." Albeit the large Cα-root mean square deviation (RMSD) of the folded protein (4.34 Å at 270 K and 4.75 Å at 304 K), a variation in tertiary structure was observed. Together with the analysis of secondary structure assignment, cluster analysis and principal component, it provides insights to the folding and unfolding pathway of 3α-fold protein and α/4β-fold protein respectively paving the way toward the understanding of the ongoings during conformational variation.

From 2012 HAITI-SIS Survey: thick-skin versus thin-skin tectonics partitioned along offshore strike-slip Faults-Haïti

NASA Astrophysics Data System (ADS)

Ellouz, N.; Leroy, S. D.; Momplaisir, R.; Mercier de Lepinay, B.

2013-12-01

The characterization of the deformation along large strike-slip fault-systems like transpressive boundaries between N. Caribbean/N America is a challenging topic, which requires a multi-scale approach. Thanks to Haiti-sis new data, the precise description of the fault segmentation pattern, the sedimentogical distribution, the uplift/subsidence rates, the along-fault and intra-basin fluids circulations, allows to actualize the evolution of the deformation history up to present-day . All the co-seismic surface to near-surface events, have to be also identified in order to integrate geophysical solutions for the earthquake, within the present-day geological and structural pattern. These two approaches, ranging from geological to instantaneous time-scales have been used during multi-tools Haiti-Sis oceanographic survey, allowing to document and image these different aspects at a large scale. The complex strike-slip North Caribbean boundary registered significative stress partitioning. Oblique convergence is expressed by along-strike evolution; from rifted segments (Cayman Through) to transpressive ones (Haiti, Dominican Rep.), to subduction (Porto Rico). In the Haiti-Sis survey, we acquired new offshore data surrounding the active fault areas, in the Gonâve Bay, the Jamaica Channel and along Southern Peninsula. Mapping the sea-floor, and HR seismic acquisition were our main objectives, in order to characterize the fault and fold architecture, with a new delineation of active segments. Offshore piston cores, have been used as representative of the modern basin sedimentation, and to document the catastrophic events (earthquakes, massive flood or sudden destabilization of the platform ) represented by turbiditic or mass-flow sequences, with the objective to track the time recurrence of seismic events by dating some of these catastrophic sediment deposition. At surface, the other markers of the fault activity are linked with along-fault permeability and fluid circulation pathway changes. Geochemical signature and temperature of the fluids and gas, change drastically depending on location and depth provenance. Our first results show that 1) the present-day EPGF geometry results from oblique shortening processes along different segments of the fault. Deep basins previously localized south and north of the fault are inverted at different degrees, 2) the Gonâve Island is only the emerged part of a NW-SE, either growing large " anti-formal stack" or basement inversion responsible for the large present-day fold amplitude, or both of them successively. It separates two sub-basins South and North Gonâve with independant sedimentary and deformation evolution 3) the Jeremie Basin probably has a specific long-living evolution, allowing to precise the geodynamic evolution of the Western Hispaniola Margin.

Origin of leucite-rich and sanidine-rich flow layers in the Leucite Hills Volcanic Field, Wyoming

NASA Astrophysics Data System (ADS)

Gunter, W. D.; Hoinkes, Georg; Ogden, Palmer; Pajari, G. E.

1990-09-01

Two types of orendite (sanidine-phlogopite lamproite) and wyomingite (leucite-phlogopite lamproite) intraflow layering are present in the ultrapotassic Leucite Hills Volcanic Field, Wyoming. In large-scale layering, wyomingites are confined to the base of the flow, while in centimeter-scale layering, orendite and wyomingite alternate throughout the flow. The mineralogy of the orendites and wyomingites are the same; only the relative amount of each mineral vary substantially. The chemical compositions of adjacent layers of wyomingite and orendite are almost identical except for water. The centimeter-scale flow layering probably represents fossil streamlines of the lava and therefore defines the path of circulation of the viscous melt. Toward the front of the flow, the layers are commonly folded. Structures present which are indicative that the flows may have possessed a yield strength are limb shears, boudinage, and slumping. Phlogopite phenocrysts are poorly aligned in the orendite layers, while they are often in subparallel alignment in the wyomingite layers; and they are used as a measure of shearing intensity during emplacement of the flow. Vesicle volumes are concentrated in the orendite layers. In the large-scale layering, a discontinuous base rubble zone of autobreccia is overlain by a thin platy zone followed by a massive zone which composes more than the upper 75% of the flow. Consequently, we feel that the origin of the layering may be related to shearing. Two extremes in the geometry of shearing are proposed: closely spaced, thin, densely sheared layers separated by discrete intervals throughout a lava flow as in the centimeter-scale layering and classical plug flow where all the shearing is confined to the base as in the large-scale layering. A mechanism is proposed which causes thixotropic behavior and localizes shearing: the driving force is the breakdown of molecular water to form T-OH bonds which establishes a chemical potential gradient for water in the melt. The higher activity of water in the nonsheared regions allows sandine to crystallize, whereas the lower activity of water in the areas of active shearing causes leucite to crystallize.

Atomic-level characterization of the structural dynamics of proteins.

PubMed

Shaw, David E; Maragakis, Paul; Lindorff-Larsen, Kresten; Piana, Stefano; Dror, Ron O; Eastwood, Michael P; Bank, Joseph A; Jumper, John M; Salmon, John K; Shan, Yibing; Wriggers, Willy

2010-10-15

Molecular dynamics (MD) simulations are widely used to study protein motions at an atomic level of detail, but they have been limited to time scales shorter than those of many biologically critical conformational changes. We examined two fundamental processes in protein dynamics--protein folding and conformational change within the folded state--by means of extremely long all-atom MD simulations conducted on a special-purpose machine. Equilibrium simulations of a WW protein domain captured multiple folding and unfolding events that consistently follow a well-defined folding pathway; separate simulations of the protein's constituent substructures shed light on possible determinants of this pathway. A 1-millisecond simulation of the folded protein BPTI reveals a small number of structurally distinct conformational states whose reversible interconversion is slower than local relaxations within those states by a factor of more than 1000.

Estimation of viscoelastic shear properties of vocal-fold tissues based on time-temperature superposition.

PubMed

Chan, R W

2001-09-01

Empirical data on the viscoelastic shear properties of human vocal-fold mucosa (cover) were recently reported at relatively low frequency (0.01-15 Hz). For the data to become relevant to voice production, attempts have been made to parametrize and extrapolate the data to higher frequencies using constitutive modeling [Chan and Titze, J. Acoust. Soc. Am. 107, 565-580 (2000)]. This study investigated the feasibility of an alternative approach for data extrapolation, namely the principle of time-temperature superposition (TTS). TTS is a hybrid theoretical-empirical approach widely used by rheologists to estimate the viscoelastic properties of polymeric systems at time or frequency scales not readily accessible experimentally. It is based on the observation that for many polymers, the molecular configurational changes that occur in a given time scale at a low temperature correspond to those that occur in a shorter time scale at a higher temperature. Using a rotational rheometer, the elastic shear modulus (G') and viscous shear modulus (G'') of vocal-fold cover (superficial layer of lamina propria) tissue samples were measured at 0.01-15 Hz at relatively low temperatures (5 degrees-37 degrees C). Data were empirically shifted according to TTS, yielding composite "master curves" for predicting the magnitude of the shear moduli at higher frequencies at 37 degrees C. Results showed that TTS may be a feasible approach for estimating the viscoelastic shear properties of vocal-fold tissues at frequencies of phonation (on the order of 100-1000 Hz).

Nonlinear viscoelastic characterization of human vocal fold tissues under large-amplitude oscillatory shear (LAOS)

PubMed Central

Chan, Roger W.

2018-01-01

Viscoelastic shear properties of human vocal fold tissues were previously quantified by the shear moduli (G′ and G″). Yet these small-strain linear measures were unable to describe any nonlinear tissue behavior. This study attempted to characterize the nonlinear viscoelastic response of the vocal fold lamina propria under large-amplitude oscillatory shear (LAOS) with a stress decomposition approach. Human vocal fold cover and vocal ligament specimens from eight subjects were subjected to LAOS rheometric testing with a simple-shear rheometer. The empirical total stress response was decomposed into elastic and viscous stress components, based on odd-integer harmonic decomposition approach with Fourier transform. Nonlinear viscoelastic measures derived from the decomposition were plotted in Pipkin space and as rheological fingerprints to observe the onset of nonlinearity and the type of nonlinear behavior. Results showed that both the vocal fold cover and the vocal ligament experienced intercycle strain softening, intracycle strain stiffening, as well as shear thinning both intercycle and intracycle. The vocal ligament appeared to demonstrate an earlier onset of nonlinearity at phonatory frequencies, and higher sensitivity to changes in frequency and strain. In summary, the stress decomposition approach provided much better insights into the nonlinear viscoelastic behavior of the vocal fold lamina propria than the traditional linear measures. PMID:29780189

Nonlinear viscoelastic characterization of human vocal fold tissues under large-amplitude oscillatory shear (LAOS).

PubMed

Chan, Roger W

2018-05-01

Viscoelastic shear properties of human vocal fold tissues were previously quantified by the shear moduli ( G' and G″ ). Yet these small-strain linear measures were unable to describe any nonlinear tissue behavior. This study attempted to characterize the nonlinear viscoelastic response of the vocal fold lamina propria under large-amplitude oscillatory shear (LAOS) with a stress decomposition approach. Human vocal fold cover and vocal ligament specimens from eight subjects were subjected to LAOS rheometric testing with a simple-shear rheometer. The empirical total stress response was decomposed into elastic and viscous stress components, based on odd-integer harmonic decomposition approach with Fourier transform. Nonlinear viscoelastic measures derived from the decomposition were plotted in Pipkin space and as rheological fingerprints to observe the onset of nonlinearity and the type of nonlinear behavior. Results showed that both the vocal fold cover and the vocal ligament experienced intercycle strain softening, intracycle strain stiffening, as well as shear thinning both intercycle and intracycle. The vocal ligament appeared to demonstrate an earlier onset of nonlinearity at phonatory frequencies, and higher sensitivity to changes in frequency and strain. In summary, the stress decomposition approach provided much better insights into the nonlinear viscoelastic behavior of the vocal fold lamina propria than the traditional linear measures.

Improving Protein Fold Recognition by Deep Learning Networks

NASA Astrophysics Data System (ADS)

Jo, Taeho; Hou, Jie; Eickholt, Jesse; Cheng, Jianlin

2015-12-01

For accurate recognition of protein folds, a deep learning network method (DN-Fold) was developed to predict if a given query-template protein pair belongs to the same structural fold. The input used stemmed from the protein sequence and structural features extracted from the protein pair. We evaluated the performance of DN-Fold along with 18 different methods on Lindahl’s benchmark dataset and on a large benchmark set extracted from SCOP 1.75 consisting of about one million protein pairs, at three different levels of fold recognition (i.e., protein family, superfamily, and fold) depending on the evolutionary distance between protein sequences. The correct recognition rate of ensembled DN-Fold for Top 1 predictions is 84.5%, 61.5%, and 33.6% and for Top 5 is 91.2%, 76.5%, and 60.7% at family, superfamily, and fold levels, respectively. We also evaluated the performance of single DN-Fold (DN-FoldS), which showed the comparable results at the level of family and superfamily, compared to ensemble DN-Fold. Finally, we extended the binary classification problem of fold recognition to real-value regression task, which also show a promising performance. DN-Fold is freely available through a web server at http://iris.rnet.missouri.edu/dnfold.

Fractal Folding and Medium Viscoelasticity Contribute Jointly to Chromosome Dynamics

NASA Astrophysics Data System (ADS)

Polovnikov, K. E.; Gherardi, M.; Cosentino-Lagomarsino, M.; Tamm, M. V.

2018-02-01

Chromosomes are key players of cell physiology, their dynamics provides valuable information about its physical organization. In both prokaryotes and eukaryotes, the short-time motion of chromosomal loci has been described with a Rouse model in a simple or viscoelastic medium. However, little emphasis has been put on the influence of the folded organization of chromosomes on the local dynamics. Clearly, stress propagation, and thus dynamics, must be affected by such organization, but a theory allowing us to extract such information from data, e.g., on two-point correlations, is lacking. Here, we describe a theoretical framework able to answer this general polymer dynamics question. We provide a scaling analysis of the stress-propagation time between two loci at a given arclength distance along the chromosomal coordinate. The results suggest a precise way to assess folding information from the dynamical coupling of chromosome segments. Additionally, we realize this framework in a specific model of a polymer whose long-range interactions are designed to make it fold in a fractal way and immersed in a medium characterized by subdiffusive fractional Langevin motion with a tunable scaling exponent. This allows us to derive explicit analytical expressions for the correlation functions.

Thin-skinned deformation of sedimentary rocks in Valles Marineris, Mars

USGS Publications Warehouse

Metz, Joannah; Grotzinger, John P.; Okubo, Chris; Milliken, Ralph

2010-01-01

Deformation of sedimentary rocks is widespread within Valles Marineris, characterized by both plastic and brittle deformation identified in Candor, Melas, and Ius Chasmata. We identified four deformation styles using HiRISE and CTX images: kilometer-scale convolute folds, detached slabs, folded strata, and pull-apart structures. Convolute folds are detached rounded slabs of material with alternating dark- and light-toned strata and a fold wavelength of about 1 km. The detached slabs are isolated rounded blocks of material, but they exhibit only highly localized evidence of stratification. Folded strata are composed of continuously folded layers that are not detached. Pull-apart structures are composed of stratified rock that has broken off into small irregularly shaped pieces showing evidence of brittle deformation. Some areas exhibit multiple styles of deformation and grade from one type of deformation into another. The deformed rocks are observed over thousands of kilometers, are limited to discrete stratigraphic intervals, and occur over a wide range in elevations. All deformation styles appear to be of likely thin-skinned origin. CRISM reflectance spectra show that some of the deformed sediments contain a component of monohydrated and polyhydrated sulfates. Several mechanisms could be responsible for the deformation of sedimentary rocks in Valles Marineris, such as subaerial or subaqueous gravitational slumping or sliding and soft sediment deformation, where the latter could include impact-induced or seismically induced liquefaction. These mechanisms are evaluated based on their expected pattern, scale, and areal extent of deformation. Deformation produced from slow subaerial or subaqueous landsliding and liquefaction is consistent with the deformation observed in Valles Marineris.

On the Origin of Protein Superfamilies and Superfolds

NASA Astrophysics Data System (ADS)

Magner, Abram; Szpankowski, Wojciech; Kihara, Daisuke

2015-02-01

Distributions of protein families and folds in genomes are highly skewed, having a small number of prevalent superfamiles/superfolds and a large number of families/folds of a small size. Why are the distributions of protein families and folds skewed? Why are there only a limited number of protein families? Here, we employ an information theoretic approach to investigate the protein sequence-structure relationship that leads to the skewed distributions. We consider that protein sequences and folds constitute an information theoretic channel and computed the most efficient distribution of sequences that code all protein folds. The identified distributions of sequences and folds are found to follow a power law, consistent with those observed for proteins in nature. Importantly, the skewed distributions of sequences and folds are suggested to have different origins: the skewed distribution of sequences is due to evolutionary pressure to achieve efficient coding of necessary folds, whereas that of folds is based on the thermodynamic stability of folds. The current study provides a new information theoretic framework for proteins that could be widely applied for understanding protein sequences, structures, functions, and interactions.

Purification of Immature Neuronal Cells from Neural Stem Cell Progeny

PubMed Central

Azari, Hassan; Osborne, Geoffrey W.; Yasuda, Takahiro; Golmohammadi, Mohammad G.; Rahman, Maryam; Deleyrolle, Loic P.; Esfandiari, Ebrahim; Adams, David J.; Scheffler, Bjorn; Steindler, Dennis A.; Reynolds, Brent A.

2011-01-01

Large-scale proliferation and multi-lineage differentiation capabilities make neural stem cells (NSCs) a promising renewable source of cells for therapeutic applications. However, the practical application for neuronal cell replacement is limited by heterogeneity of NSC progeny, relatively low yield of neurons, predominance of astrocytes, poor survival of donor cells following transplantation and the potential for uncontrolled proliferation of precursor cells. To address these impediments, we have developed a method for the generation of highly enriched immature neurons from murine NSC progeny. Adaptation of the standard differentiation procedure in concert with flow cytometry selection, using scattered light and positive fluorescent light selection based on cell surface antibody binding, provided a near pure (97%) immature neuron population. Using the purified neurons, we screened a panel of growth factors and found that bone morphogenetic protein-4 (BMP-4) demonstrated a strong survival effect on the cells in vitro, and enhanced their functional maturity. This effect was maintained following transplantation into the adult mouse striatum where we observed a 2-fold increase in the survival of the implanted cells and a 3-fold increase in NeuN expression. Additionally, based on the neural-colony forming cell assay (N-CFCA), we noted a 64 fold reduction of the bona fide NSC frequency in neuronal cell population and that implanted donor cells showed no signs of excessive or uncontrolled proliferation. The ability to provide defined neural cell populations from renewable sources such as NSC may find application for cell replacement therapies in the central nervous system. PMID:21687800

Purification and properties of recombinant exopolyphosphatase PPN1 and effects of its overexpression on polyphosphate in Saccharomyces cerevisiae.

PubMed

Andreeva, Nadeshda; Trilisenko, Ludmila; Kulakovskaya, Tatiana; Dumina, Maria; Eldarov, Michail

2015-01-01

Inorganic polyphosphate performs many regulatory functions in living cells. The yeast exopolyphosphatase PPN1 is an enzyme with multiple cellular localization and probably variable functions. The Saccharomyces cerevisiae strain with overexpressed PPN1 was constructed for large-scale production of the enzyme and for studying the effect of overproduction on polyphosphate metabolism. The ΔPPN1 strain was transformed by the vector containing this gene under a strong constitutive promoter of glycerol aldehyde-triphosphate dehydrogenase of S. cerevisiae. Exopolyphosphatase activity in the transformant increased 28- and 11-fold compared to the ΔPPN1 and parent strains, respectively. The content of acid-soluble polyphosphate decreased ∼6-fold and the content of acid-insoluble polyphosphate decreased ∼2.5-fold in the cells of the transformant compared to the ΔPPN1 strain. The recombinant enzyme was purified. The substrate specificity, cation requirement, and inhibition by heparin were found to be similar to native PPN1. The molecular mass of a subunit (∼33 kD) and the amino acid sequence of the recombinant enzyme were the same as in mature PPN1. The recombinant enzyme was localized mainly in the cytoplasm (40%) and vacuoles (20%). The overproducer strain had no growths defects under phosphate deficiency or phosphate excess. In contrast to the parent strains accumulating polyphosphate, the transformant accumulated orthophosphate under phosphate surplus. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Large scale isolation, growth, and function of porcine neonatal islet cells.

PubMed Central

Korbutt, G S; Elliott, J F; Ao, Z; Smith, D K; Warnock, G L; Rajotte, R V

1996-01-01

Based upon existing methods of isolating fetal porcine islet tissue, a simple, reliable procedure was developed for the preparation of porcine neonatal islet cell aggregates with a reproducible and defined cellular composition. After 9 d of in vitro culture, tissue from one neonatal pig pancreas yielded approximately 50,000 islet cell aggregates, consisting of primarily epithelial cells (57%) and pancreatic endocrine cells (35%). During the culture period, the total beta cell mass decreased initially, but subsequently increased 1.5-fold between days 3 and 9. Transplantation of grafts consisting of 3 x 10(5) beta cells (1,000 aggregated) under the kidney capsule of alloxan-diabetic nude mice corrected hyperglycemia in 75% (10/13) of the animals, whereas, 100% (20/20) of recipients implanted with 6 x 10(5) beta cells (2,000 aggregates) achieved euglycemia within 8 wk posttransplantation. Nephrectomy of the graft bearing kidney at 14 wk posttransplantation resulted in hyperglycemia in all recipients, and examination of the grafts revealed the presence of numerous well-granulated insulin- and glucagon-containing cells. The cellular insulin content of these grafts was 20 to 30-fold higher than at the time of transplantation. These results indicate that the neonatal porcine pancrease can be used as a source of large numbers of viable islet cells, which have the potential for growth both in vitro and in vivo, and exhibit the metabolic capacity to correct diabetes in nude mice. PMID:8621802

Haustral fold registration in CT colonography and its application to registration of virtual stretched view of the colon

NASA Astrophysics Data System (ADS)

Fukano, Eiichiro; Oda, Masahiro; Kitasaka, Takayuki; Suenaga, Yasuhito; Takayama, Tetsuji; Takabatake, Hirotsugu; Mori, Masaki; Natori, Hiroshi; Nawano, Shigeru; Mori, Kensaku

2010-03-01

This paper proposes a method for making correspondence between the supine and the prone positions of the colon in CT volumes. In CT colonography, two CT volumes in the supine and the prone positions are often taken to observe the whole colonic wall by comparing them. However, the colonic wall is soft and changes its shape when a patient changes positions. Therefore, physicians need to take the positional relations into account when comparing the two CT volumes. Calculation of the positional relations between the two positions of the colon can reduce load of physicians. A large number of haustral folds exists in the colon and the order doesn't change even when a patient change positions. Therefore, haustral folds are suitable for registering the supine and the prone positions of the colon. We also find sharply bending points of the centerline of the colon as landmarks for brief registration. The precise registration is then performed by finding positional correspondence of the haustral folds in the supine and the prone positions. In correspondence search, we first find the correspondence among long haustral folds, followed by small haustral folds. As the result of experiment using six pairs of 3D abdominal CT volumes, 65.1% of the correspondence of large haustral folds were correct, 25.6% were incorrect, and 9.3% could not be judged. On the other hand, 13.3% of the correspondence of small haustral folds were correct, 42.9% were incorrect, and 32.7% could not be judged.

Sophia: A Expedient UMLS Concept Extraction Annotator.

PubMed

Divita, Guy; Zeng, Qing T; Gundlapalli, Adi V; Duvall, Scott; Nebeker, Jonathan; Samore, Matthew H

2014-01-01

An opportunity exists for meaningful concept extraction and indexing from large corpora of clinical notes in the Veterans Affairs (VA) electronic medical record. Currently available tools such as MetaMap, cTAKES and HITex do not scale up to address this big data need. Sophia, a rapid UMLS concept extraction annotator was developed to fulfill a mandate and address extraction where high throughput is needed while preserving performance. We report on the development, testing and benchmarking of Sophia against MetaMap and cTAKEs. Sophia demonstrated improved performance on recall as compared to cTAKES and MetaMap (0.71 vs 0.66 and 0.38). The overall f-score was similar to cTAKES and an improvement over MetaMap (0.53 vs 0.57 and 0.43). With regard to speed of processing records, we noted Sophia to be several fold faster than cTAKES and the scaled-out MetaMap service. Sophia offers a viable alternative for high-throughput information extraction tasks.

Novel Solar Photocatalytic Reactor for Wastewater Treatment

NASA Astrophysics Data System (ADS)

Sutisna; Rokhmat, M.; Wibowo, E.; Murniati, R.; Khairurrijal; Abdullah, M.

2017-07-01

A new solar photocatalytic reactor (photoreactor) using TiO2 nanoparticles coated onto plastic granules has been designed. Catalyst granules are placed into the cavity of a reactor panel made of glass. A pump is used to circulate wastewater in the photoreactor. Methylene blue (MB) dissolved in water was chosen as the wastewater model. The performance of the photoreactor was evaluated based on changes in MB concentration with respect to time. The photoreactor showed a good performance by degrading 10 L of MB solution up to 96.54% after 48 h of solar irradiation. The photoreactor was scaled up by enlarging the panel area to twice its original size. The increase in the surface area of the reactor panel and therefore of the mass of catalyst granules and reactor volume led to a three-fold increase of the photodegradation rate. In addition, the MB degradation kinetics were also studied. Data analysis confirmed the applicability of the pseudo-first-order Langmuir-Hinshelwood model. The proposed photoreactor has great potential for use in large-scale wastewater treatment.

Sophia: A Expedient UMLS Concept Extraction Annotator

PubMed Central

Divita, Guy; Zeng, Qing T; Gundlapalli, Adi V.; Duvall, Scott; Nebeker, Jonathan; Samore, Matthew H.

2014-01-01

An opportunity exists for meaningful concept extraction and indexing from large corpora of clinical notes in the Veterans Affairs (VA) electronic medical record. Currently available tools such as MetaMap, cTAKES and HITex do not scale up to address this big data need. Sophia, a rapid UMLS concept extraction annotator was developed to fulfill a mandate and address extraction where high throughput is needed while preserving performance. We report on the development, testing and benchmarking of Sophia against MetaMap and cTAKEs. Sophia demonstrated improved performance on recall as compared to cTAKES and MetaMap (0.71 vs 0.66 and 0.38). The overall f-score was similar to cTAKES and an improvement over MetaMap (0.53 vs 0.57 and 0.43). With regard to speed of processing records, we noted Sophia to be several fold faster than cTAKES and the scaled-out MetaMap service. Sophia offers a viable alternative for high-throughput information extraction tasks. PMID:25954351

Simulating Metabolism with Statistical Thermodynamics

PubMed Central

Cannon, William R.

2014-01-01

New methods are needed for large scale modeling of metabolism that predict metabolite levels and characterize the thermodynamics of individual reactions and pathways. Current approaches use either kinetic simulations, which are difficult to extend to large networks of reactions because of the need for rate constants, or flux-based methods, which have a large number of feasible solutions because they are unconstrained by the law of mass action. This report presents an alternative modeling approach based on statistical thermodynamics. The principles of this approach are demonstrated using a simple set of coupled reactions, and then the system is characterized with respect to the changes in energy, entropy, free energy, and entropy production. Finally, the physical and biochemical insights that this approach can provide for metabolism are demonstrated by application to the tricarboxylic acid (TCA) cycle of Escherichia coli. The reaction and pathway thermodynamics are evaluated and predictions are made regarding changes in concentration of TCA cycle intermediates due to 10- and 100-fold changes in the ratio of NAD+:NADH concentrations. Finally, the assumptions and caveats regarding the use of statistical thermodynamics to model non-equilibrium reactions are discussed. PMID:25089525

Simulating metabolism with statistical thermodynamics.

PubMed

Cannon, William R

2014-01-01

New methods are needed for large scale modeling of metabolism that predict metabolite levels and characterize the thermodynamics of individual reactions and pathways. Current approaches use either kinetic simulations, which are difficult to extend to large networks of reactions because of the need for rate constants, or flux-based methods, which have a large number of feasible solutions because they are unconstrained by the law of mass action. This report presents an alternative modeling approach based on statistical thermodynamics. The principles of this approach are demonstrated using a simple set of coupled reactions, and then the system is characterized with respect to the changes in energy, entropy, free energy, and entropy production. Finally, the physical and biochemical insights that this approach can provide for metabolism are demonstrated by application to the tricarboxylic acid (TCA) cycle of Escherichia coli. The reaction and pathway thermodynamics are evaluated and predictions are made regarding changes in concentration of TCA cycle intermediates due to 10- and 100-fold changes in the ratio of NAD+:NADH concentrations. Finally, the assumptions and caveats regarding the use of statistical thermodynamics to model non-equilibrium reactions are discussed.