Linear Classifier with Reject Option for the Detection of Vocal Fold Paralysis and Vocal Fold Edema

NASA Astrophysics Data System (ADS)

Kotropoulos, Constantine; Arce, Gonzalo R.

2009-12-01

Two distinct two-class pattern recognition problems are studied, namely, the detection of male subjects who are diagnosed with vocal fold paralysis against male subjects who are diagnosed as normal and the detection of female subjects who are suffering from vocal fold edema against female subjects who do not suffer from any voice pathology. To do so, utterances of the sustained vowel "ah" are employed from the Massachusetts Eye and Ear Infirmary database of disordered speech. Linear prediction coefficients extracted from the aforementioned utterances are used as features. The receiver operating characteristic curve of the linear classifier, that stems from the Bayes classifier when Gaussian class conditional probability density functions with equal covariance matrices are assumed, is derived. The optimal operating point of the linear classifier is specified with and without reject option. First results using utterances of the "rainbow passage" are also reported for completeness. The reject option is shown to yield statistically significant improvements in the accuracy of detecting the voice pathologies under study.

Computation of the three-dimensional medial surface dynamics of the vocal folds.

PubMed

Döllinger, Michael; Berry, David A

2006-01-01

To increase our understanding of pathological and healthy voice production, quantitative measurement of the medial surface dynamics of the vocal folds is significant, albeit rarely performed because of the inaccessibility of the vocal folds. Using an excised hemilarynx methodology, a new calibration technique, herein referred to as the linear approximate (LA) method, was introduced to compute the three-dimensional coordinates of fleshpoints along the entire medial surface of the vocal fold. The results were compared with results from the direct linear transform. An associated error estimation was presented, demonstrating the improved accuracy of the new method. A test on real data was reported including computation of quantitative measurements of vocal fold dynamics.

Aromatic Cluster Sensor of Protein Folding: Near-UV Electronic Circular Dichroism Bands Assigned to Fold Compactness.

PubMed

Farkas, Viktor; Jákli, Imre; Tóth, Gábor K; Perczel, András

2016-09-19

Both far- and near-UV electronic circular dichroism (ECD) spectra have bands sensitive to thermal unfolding of Trp and Tyr residues containing proteins. Beside spectral changes at 222 nm reporting secondary structural variations (far-UV range), L b bands (near-UV range) are applicable as 3D-fold sensors of protein's core structure. In this study we show that both L b (Tyr) and L b (Trp) ECD bands could be used as sensors of fold compactness. ECD is a relative method and thus requires NMR referencing and cross-validation, also provided here. The ensemble of 204 ECD spectra of Trp-cage miniproteins is analysed as a training set for "calibrating" Trp↔Tyr folded systems of known NMR structure. While in the far-UV ECD spectra changes are linear as a function of the temperature, near-UV ECD data indicate a non-linear and thus, cooperative unfolding mechanism of these proteins. Ensemble of ECD spectra deconvoluted gives both conformational weights and insight to a protein folding↔unfolding mechanism. We found that the L b 293 band is reporting on the 3D-structure compactness. In addition, the pure near-UV ECD spectrum of the unfolded state is described here for the first time. Thus, ECD folding information now validated can be applied with confidence in a large thermal window (5≤T≤85 °C) compared to NMR for studying the unfolding of Trp↔Tyr residue pairs. In conclusion, folding propensities of important proteins (RNA polymerase II, ubiquitin protein ligase, tryptase-inhibitor etc.) can now be analysed with higher confidence. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A universal molecular clock of protein folds and its power in tracing the early history of aerobic metabolism and planet oxygenation.

PubMed

Wang, Minglei; Jiang, Ying-Ying; Kim, Kyung Mo; Qu, Ge; Ji, Hong-Fang; Mittenthal, Jay E; Zhang, Hong-Yu; Caetano-Anollés, Gustavo

2011-01-01

The standard molecular clock describes a constant rate of molecular evolution and provides a powerful framework for evolutionary timescales. Here, we describe the existence and implications of a molecular clock of folds, a universal recurrence in the discovery of new structures in the world of proteins. Using a phylogenomic structural census in hundreds of proteomes, we build phylogenies and time lines of domains at fold and fold superfamily levels of structural complexity. These time lines correlate approximately linearly with geological timescales and were here used to date two crucial events in life history, planet oxygenation and organism diversification. We first dissected the structures and functions of enzymes in simulated metabolic networks. The placement of anaerobic and aerobic enzymes in the time line revealed that aerobic metabolism emerged about 2.9 billion years (giga-annum; Ga) ago and expanded during a period of about 400 My, reaching what is known as the Great Oxidation Event. During this period, enzymes recruited old and new folds for oxygen-mediated enzymatic activities. Remarkably, the first fold lost by a superkingdom disappeared in Archaea 2.6 Ga ago, within the span of oxygen rise, suggesting that oxygen also triggered diversification of life. The implications of a molecular clock of folds are many and important for the neutral theory of molecular evolution and for understanding the growth and diversity of the protein world. The clock also extends the standard concept that was specific to molecules and their timescales and turns it into a universal timescale-generating tool.

Quantifying the influence of flow asymmetries on glottal sound sources in speech

NASA Astrophysics Data System (ADS)

Erath, Byron; Plesniak, Michael

2008-11-01

Human speech is made possible by the air flow interaction with the vocal folds. During phonation, asymmetries in the glottal flow field may arise from flow phenomena (e.g. the Coanda effect) as well as from pathological vocal fold motion (e.g. unilateral paralysis). In this study, the effects of flow asymmetries on glottal sound sources were investigated. Dynamically-programmable 7.5 times life-size vocal fold models with 2 degrees-of-freedom (linear and rotational) were constructed to provide a first-order approximation of vocal fold motion. Important parameters (Reynolds, Strouhal, and Euler numbers) were scaled to physiological values. Normal and abnormal vocal fold motions were synthesized, and the velocity field and instantaneous transglottal pressure drop were measured. Variability in the glottal jet trajectory necessitated sorting of the data according to the resulting flow configuration. The dipole sound source is related to the transglottal pressure drop via acoustic analogies. Variations in the transglottal pressure drop (and subsequently the dipole sound source) arising from flow asymmetries are discussed.

Predicting folding-unfolding transitions in proteins without a priori knowledge of the folded state

NASA Astrophysics Data System (ADS)

Okan, Osman; Turgut, Deniz; Garcia, Angel; Ozisik, Rahmi

2013-03-01

The common computational method of studying folding transitions in proteins is to compare simulated conformations against the folded structure, but this method obviously requires the folded structure to be known beforehand. In the current study, we show that the use of bond orientational order parameter (BOOP) Ql [Steinhardt PJ, Nelson DR, Ronchetti M, Phys. Rev. B 1983, 28, 784] is a viable alternative to the commonly adopted root mean squared distance (RMSD) measure in probing conformational transitions. Replica exchange molecular dynamics simulations of the trp-cage protein (with 20 residues) in TIP-3P water were used to compare BOOP against RMSD. The results indicate that the correspondence between BOOP and RMSD time series become stronger with increasing l. We finally show that robust linear models that incorporate different Ql can be parameterized from a given replica run and can be used to study other replica trajectories. This work is partially supported by NSF DUE-1003574.

Circuit topology of proteins and nucleic acids.

PubMed

Mashaghi, Alireza; van Wijk, Roeland J; Tans, Sander J

2014-09-02

Folded biomolecules display a bewildering structural complexity and diversity. They have therefore been analyzed in terms of generic topological features. For instance, folded proteins may be knotted, have beta-strands arranged into a Greek-key motif, or display high contact order. In this perspective, we present a method to formally describe the topology of all folded linear chains and hence provide a general classification and analysis framework for a range of biomolecules. Moreover, by identifying the fundamental rules that intrachain contacts must obey, the method establishes the topological constraints of folded linear chains. We also briefly illustrate how this circuit topology notion can be applied to study the equivalence of folded chains, the engineering of artificial RNA structures and DNA origami, the topological structure of genomes, and the role of topology in protein folding. Copyright © 2014 Elsevier Ltd. All rights reserved.

STRONG ORACLE OPTIMALITY OF FOLDED CONCAVE PENALIZED ESTIMATION.

PubMed

Fan, Jianqing; Xue, Lingzhou; Zou, Hui

2014-06-01

Folded concave penalization methods have been shown to enjoy the strong oracle property for high-dimensional sparse estimation. However, a folded concave penalization problem usually has multiple local solutions and the oracle property is established only for one of the unknown local solutions. A challenging fundamental issue still remains that it is not clear whether the local optimum computed by a given optimization algorithm possesses those nice theoretical properties. To close this important theoretical gap in over a decade, we provide a unified theory to show explicitly how to obtain the oracle solution via the local linear approximation algorithm. For a folded concave penalized estimation problem, we show that as long as the problem is localizable and the oracle estimator is well behaved, we can obtain the oracle estimator by using the one-step local linear approximation. In addition, once the oracle estimator is obtained, the local linear approximation algorithm converges, namely it produces the same estimator in the next iteration. The general theory is demonstrated by using four classical sparse estimation problems, i.e., sparse linear regression, sparse logistic regression, sparse precision matrix estimation and sparse quantile regression.

STRONG ORACLE OPTIMALITY OF FOLDED CONCAVE PENALIZED ESTIMATION

PubMed Central

Fan, Jianqing; Xue, Lingzhou; Zou, Hui

2014-01-01

Folded concave penalization methods have been shown to enjoy the strong oracle property for high-dimensional sparse estimation. However, a folded concave penalization problem usually has multiple local solutions and the oracle property is established only for one of the unknown local solutions. A challenging fundamental issue still remains that it is not clear whether the local optimum computed by a given optimization algorithm possesses those nice theoretical properties. To close this important theoretical gap in over a decade, we provide a unified theory to show explicitly how to obtain the oracle solution via the local linear approximation algorithm. For a folded concave penalized estimation problem, we show that as long as the problem is localizable and the oracle estimator is well behaved, we can obtain the oracle estimator by using the one-step local linear approximation. In addition, once the oracle estimator is obtained, the local linear approximation algorithm converges, namely it produces the same estimator in the next iteration. The general theory is demonstrated by using four classical sparse estimation problems, i.e., sparse linear regression, sparse logistic regression, sparse precision matrix estimation and sparse quantile regression. PMID:25598560

Stereoselective pharmacokinetic study of rhynchophylline and isorhynchophylline epimers in rat plasma by liquid chromatography-tandem mass spectrometry.

PubMed

Wang, Xin; Zheng, Mei; Liu, Jia; Qiao, Zhou; Liu, Wenyuan; Feng, Feng

2017-06-01

1. In this study, the stereoselective pharmacokinetics of rhynchophylline (RIN) and isorhynchophylline (IRN) in rat plasma were investigated using liquid chromatography-tandem mass spectrometry (LC-MS/MS). 2. A rapid, robust and sensitive LC-MS/MS method for simultaneous quantification of RIN and IRN in rat plasma was established and validated. Chromatographic separation was performed on a Poroshell 120 EC-C 18 column under a gradient elution with methanol and water containing 0.01% ammonia as mobile phase. Calibration curve was linear over a concentration range of 1-2000 ng/mL for both epimers. 3. After intravenous administration, there was no apparent difference in pharmacokinetic parameters between two epimers. However, after oral administration, RIN showed remarkable higher plasma exposure than IRN. The bioavailability, C max and AUC 0- t of RIN were about 9.2-fold, 6.4-fold and 9.1-fold higher than those of IRN at 10 mg/kg, and 7.8-fold, 4.3-fold and 7.7-fold at 20 mg/kg, respectively. Additionally, with dosage enhanced from 10 mg/kg to 20 mg/kg, the plasma concentrations of RIN or IRN increased significantly and the bioavailability enhanced about three times. 4. In conclusion, the results of this work demonstrated for the first time that the pharmacokinetics of RIN and IRN have stereoselectivity.

Circuit topology of self-interacting chains: implications for folding and unfolding dynamics.

PubMed

Mugler, Andrew; Tans, Sander J; Mashaghi, Alireza

2014-11-07

Understanding the relationship between molecular structure and folding is a central problem in disciplines ranging from biology to polymer physics and DNA origami. Topology can be a powerful tool to address this question. For a folded linear chain, the arrangement of intra-chain contacts is a topological property because rearranging the contacts requires discontinuous deformations. Conversely, the topology is preserved when continuously stretching the chain while maintaining the contact arrangement. Here we investigate how the folding and unfolding of linear chains with binary contacts is guided by the topology of contact arrangements. We formalize the topology by describing the relations between any two contacts in the structure, which for a linear chain can either be in parallel, in series, or crossing each other. We show that even when other determinants of folding rate such as contact order and size are kept constant, this 'circuit' topology determines folding kinetics. In particular, we find that the folding rate increases with the fractions of parallel and crossed relations. Moreover, we show how circuit topology constrains the conformational phase space explored during folding and unfolding: the number of forbidden unfolding transitions is found to increase with the fraction of parallel relations and to decrease with the fraction of series relations. Finally, we find that circuit topology influences whether distinct intermediate states are present, with crossed contacts being the key factor. The approach presented here can be more generally applied to questions on molecular dynamics, evolutionary biology, molecular engineering, and single-molecule biophysics.

Investigations into the Effect of Current Velocity on Amidoxime-Based Polymeric Uranium Adsorbent Performance

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

Gill, Gary A.; Kuo, Li-Jung; Strivens, Jonathan E.

2015-12-01

The Fuel Resources Program at the U.S. Department of Energy’s (DOE), Office of Nuclear Energy (DOE-NE) is developing adsorbent technology to extract uranium from seawater. This technology is being developed to provide a sustainable and economically viable supply of uranium fuel for nuclear reactors (DOE, 2010). Among the key environmental variables to understand for adsorbent deployment in the coastal ocean is what effect flow-rates or linear velocity has on uranium adsorption capacity. The goal is to find a flow conditions that optimize uranium adsorption capacity in the shortest exposure time. Understanding these criteria will be critical in choosing a locationmore » for deployment of a marine adsorbent farm. The objective of this study was to identify at what linear velocity the adsorption kinetics for uranium extraction starts to drop off due to limitations in mass transport of uranium to the surface of the adsorbent fibers. Two independent laboratory-based experimental approaches using flow-through columns and recirculating flumes for adsorbent exposure were used to assess the effect of flow-rate (linear velocity) on the kinetic uptake of uranium on amidoxime-based polymeric adsorbent material. Time series observations over a 56 day period were conducted with flow-through columns over a 35-fold range in linear velocity from 0.29 to 10.2 cm/s, while the flume study was conducted over a narrower 11-fold range, from 0.48 to 5.52 cm/s. These ranges were specifically chosen to focus on the lower end of oceanic currents and expand above and below the linear velocity of ~ 2.5 cm/s adopted for marine testing of adsorbent material at PNNL.« less

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…

Constriction structures related to viscous collision, southern Prince Charles Mountains, Antarctica

NASA Astrophysics Data System (ADS)

Corvino, Adrian F.; Boger, Steven D.; Fay, Clement

2016-09-01

Macroscopic structures are investigated in a zone of highly contorted migmatites from the southern Prince Charles Mountains, Antarctica. Here, L-tectonite fabrics, rods, mullions, boudin pods, elongate enclaves, and fold hinges, are persistent linear features all plunging gently to the northeast. In contrast, amoeboid folds, ptygmatic folds and folded boudins with different orientations are the characteristic structures in transverse sections (perpendicular to the lineation). No consistent shear sense is recognised in any dimension. Together with strain and shape analysis, these observations strongly suggest that the deformation pattern is one of folding and stretching by constriction. Previous timing constraints indicate that this deformation overlapped with the waning stages of anatexis during decompression at approximately 510 Ma, up to 30 million years after initial orogeny at 540 Ma. The zone affected by constriction is several kilometres wide and has a contorted flower-like shape confined between two broad domal antiforms. In this context, the constricted zone is interpreted as a relatively late tectonic feature that could have formed via deep-seated viscous collision in response to orogenic collapse and doming.

A simple-shear rheometer for linear viscoelastic characterization of vocal fold tissues at phonatory frequencies.

PubMed

Chan, Roger W; Rodriguez, Maritza L

2008-08-01

Previous studies reporting the linear viscoelastic shear properties of the human vocal fold cover or mucosa have been based on torsional rheometry, with measurements limited to low audio frequencies, up to around 80 Hz. This paper describes the design and validation of a custom-built, controlled-strain, linear, simple-shear rheometer system capable of direct empirical measurements of viscoelastic shear properties at phonatory frequencies. A tissue specimen was subjected to simple shear between two parallel, rigid acrylic plates, with a linear motor creating a translational sinusoidal displacement of the specimen via the upper plate, and the lower plate transmitting the harmonic shear force resulting from the viscoelastic response of the specimen. The displacement of the specimen was measured by a linear variable differential transformer whereas the shear force was detected by a piezoelectric transducer. The frequency response characteristics of these system components were assessed by vibration experiments with accelerometers. Measurements of the viscoelastic shear moduli (G' and G") of a standard ANSI S2.21 polyurethane material and those of human vocal fold cover specimens were made, along with estimation of the system signal and noise levels. Preliminary results showed that the rheometer can provide valid and reliable rheometric data of vocal fold lamina propria specimens at frequencies of up to around 250 Hz, well into the phonatory range.

Modelling of lateral fold growth and fold linkage: Applications to fold-and-thrust belt tectonics

NASA Astrophysics Data System (ADS)

Grasemann, Bernhard; Schmalholz, Stefan

2013-04-01

We use a finite element model to investigate the three-dimensional fold growth and interference of two initially isolated fold segments. The most critical parameter, which controls the fold linkage mode, is the phase difference between the laterally growing fold hinge lines: 1) "Linear-linkage" yields a sub-cylindrical fold with a saddle at the location where the two initial folds linked. 2) "Oblique-linkage" produces a curved fold resembling a Type II refold structure. 3) "Oblique-no-linkage" results in two curved folds with fold axes plunging in opposite directions. 4) "Linear-no-linkage" yields a fold train of two separate sub-cylindrical folds with fold axes plunging in opposite directions. The transition from linkage to no-linkage occurs when the fold separation between the initially isolated folds is slightly larger than one half of the low-amplitude fold wavelength. The model results compare well with previously published plasticine analogue models and can be directly applied to the investigation of fold growth history in fold-and-thust belts. An excellent natural example of lateral fold linkage is described from the Zagros fold-and-thrust belt in the Kurdistan Region of Iraq. The fold growth in this region is not controlled by major thrust faults but the shortening of the Paleozoic to Cenozoic passive margin sediments of the Arabian plate occurred mainly by detachment folding. The sub-cylindrical anticlines with hinge-parallel lengths of more than 50 km have not developed from single sub-cylindrical embryonic folds but they have merged from different fold segments that joined laterally during fold amplification and lateral fold growth. Linkage points are marked by geomorphological saddle points which are structurally the lowermost points of antiforms and points of principal curvatures with opposite sign. Linkage points can significantly influence the migration of mineral-rich fluids and hydrocarbons and are therefore of great economic importance.

Comparison of esterase gene amplification, gene expression and esterase activity in insecticide susceptible and resistant strains of the brown planthopper, Nilaparvata lugens (Stål).

PubMed

Vontas, J G; Small, G J; Hemingway, J

2000-12-01

Organophosphorus and carbamate insecticide resistance in Nilaparvata lugens is based on amplification of a carboxylesterase gene, Nl-EST1. An identical gene occurs in susceptible insects. Quantitative real-time PCR was used to demonstrate that Nl-EST1 is amplified 3-7-fold in the genome of resistant compared to susceptible planthoppers. Expression levels were similar to amplification levels, with 1-15-fold more Nl-EST1 mRNA in individual insects and 5-11-fold more Nl-EST1 mRNA in mass whole body homogenates of resistant females compared to susceptibles. These values corresponded to an 8-10-fold increase in esterase activity in the head and thorax of individual resistant insects. Although amplification, expression and activity levels of Nl-EST1 in resistant N. lugens were similar, the correlation between esterase activity and Nl-EST1 mRNA levels in resistant individuals was not linear.

Study of non-linear deformation of vocal folds in simulations of human phonation

NASA Astrophysics Data System (ADS)

Saurabh, Shakti; Bodony, Daniel

2014-11-01

Direct numerical simulation is performed on a two-dimensional compressible, viscous fluid interacting with a non-linear, viscoelastic solid as a model for the generation of the human voice. The vocal fold (VF) tissues are modeled as multi-layered with varying stiffness in each layer and using a finite-strain Standard Linear Solid (SLS) constitutive model implemented in a quadratic finite element code and coupled to a high-order compressible Navier-Stokes solver through a boundary-fitted fluid-solid interface. The large non-linear mesh deformation is handled using an elliptic/poisson smoothening technique. Supra-glottal flow shows asymmetry in the flow, which in turn has a coupling effect on the motion of the VF. The fully compressible simulations gives direct insight into the sound produced as pressure distributions and the vocal fold deformation helps study the unsteady vortical flow resulting from the fluid-structure interaction along the full phonation cycle. Supported by the National Science Foundation (CAREER Award Number 1150439).

Highly-accelerated quantitative 2D and 3D localized spectroscopy with linear algebraic modeling (SLAM) and sensitivity encoding

NASA Astrophysics Data System (ADS)

Zhang, Yi; Gabr, Refaat E.; Zhou, Jinyuan; Weiss, Robert G.; Bottomley, Paul A.

2013-12-01

Noninvasive magnetic resonance spectroscopy (MRS) with chemical shift imaging (CSI) provides valuable metabolic information for research and clinical studies, but is often limited by long scan times. Recently, spectroscopy with linear algebraic modeling (SLAM) was shown to provide compartment-averaged spectra resolved in one spatial dimension with many-fold reductions in scan-time. This was achieved using a small subset of the CSI phase-encoding steps from central image k-space that maximized the signal-to-noise ratio. Here, SLAM is extended to two- and three-dimensions (2D, 3D). In addition, SLAM is combined with sensitivity-encoded (SENSE) parallel imaging techniques, enabling the replacement of even more CSI phase-encoding steps to further accelerate scan-speed. A modified SLAM reconstruction algorithm is introduced that significantly reduces the effects of signal nonuniformity within compartments. Finally, main-field inhomogeneity corrections are provided, analogous to CSI. These methods are all tested on brain proton MRS data from a total of 24 patients with brain tumors, and in a human cardiac phosphorus 3D SLAM study at 3T. Acceleration factors of up to 120-fold versus CSI are demonstrated, including speed-up factors of 5-fold relative to already-accelerated SENSE CSI. Brain metabolites are quantified in SLAM and SENSE SLAM spectra and found to be indistinguishable from CSI measures from the same compartments. The modified reconstruction algorithm demonstrated immunity to maladjusted segmentation and errors from signal heterogeneity in brain data. In conclusion, SLAM demonstrates the potential to supplant CSI in studies requiring compartment-average spectra or large volume coverage, by dramatically reducing scan-time while providing essentially the same quantitative results.

Determination of real-time polymerase chain reaction uncertainty of measurement using replicate analysis and a graphical user interface with Fieller’s theorem

PubMed Central

Stuart, James Ian; Delport, Johan; Lannigan, Robert; Zahariadis, George

2014-01-01

BACKGROUND: Disease monitoring of viruses using real-time polymerase chain reaction (PCR) requires knowledge of the precision of the test to determine what constitutes a significant change. Calculation of quantitative PCR confidence limits requires bivariate statistical methods. OBJECTIVE: To develop a simple-to-use graphical user interface to determine the uncertainty of measurement (UOM) of BK virus, cytomegalovirus (CMV) and Epstein-Barr virus (EBV) real-time PCR assays. METHODS: Thirty positive clinical samples for each of the three viral assays were repeated once. A graphical user interface was developed using a spreadsheet (Excel, Microsoft Corporation, USA) to enable data entry and calculation of the UOM (according to Fieller’s theorem) and PCR efficiency. RESULTS: The confidence limits for the BK virus, CMV and EBV tests were ∼0.5 log, 0.5 log to 1.0 log, and 0.5 log to 1.0 log, respectively. The efficiencies of these assays, in the same order were 105%, 119% and 90%. The confidence limits remained stable over the linear range of all three tests. DISCUSSION: A >5 fold (0.7 log) and a >3-fold (0.5 log) change in viral load were significant for CMV and EBV when the results were ≤1000 copies/mL and >1000 copies/mL, respectively. A >3-fold (0.5 log) change in viral load was significant for BK virus over its entire linear range. PCR efficiency was ideal for BK virus and EBV but not CMV. Standardized international reference materials and shared reporting of UOM among laboratories are required for the development of treatment guidelines for BK virus, CMV and EBV in the context of changes in viral load. PMID:25285125

Determination of real-time polymerase chain reaction uncertainty of measurement using replicate analysis and a graphical user interface with Fieller's theorem.

PubMed

Stuart, James Ian; Delport, Johan; Lannigan, Robert; Zahariadis, George

2014-07-01

Disease monitoring of viruses using real-time polymerase chain reaction (PCR) requires knowledge of the precision of the test to determine what constitutes a significant change. Calculation of quantitative PCR confidence limits requires bivariate statistical methods. To develop a simple-to-use graphical user interface to determine the uncertainty of measurement (UOM) of BK virus, cytomegalovirus (CMV) and Epstein-Barr virus (EBV) real-time PCR assays. Thirty positive clinical samples for each of the three viral assays were repeated once. A graphical user interface was developed using a spreadsheet (Excel, Microsoft Corporation, USA) to enable data entry and calculation of the UOM (according to Fieller's theorem) and PCR efficiency. The confidence limits for the BK virus, CMV and EBV tests were ∼0.5 log, 0.5 log to 1.0 log, and 0.5 log to 1.0 log, respectively. The efficiencies of these assays, in the same order were 105%, 119% and 90%. The confidence limits remained stable over the linear range of all three tests. A >5 fold (0.7 log) and a >3-fold (0.5 log) change in viral load were significant for CMV and EBV when the results were ≤1000 copies/mL and >1000 copies/mL, respectively. A >3-fold (0.5 log) change in viral load was significant for BK virus over its entire linear range. PCR efficiency was ideal for BK virus and EBV but not CMV. Standardized international reference materials and shared reporting of UOM among laboratories are required for the development of treatment guidelines for BK virus, CMV and EBV in the context of changes in viral load.

Stress and strain evolution of folding rocks

NASA Astrophysics Data System (ADS)

Llorens, Maria-Gema; Griera, Albert; Bons, Paul; Gomez-Rivas, Enrique; Weikusat, Ilka

2015-04-01

One of the main objectives of structural geology is to unravel rock deformation histories. Fold shapes can be used to estimate the orientation and amount of strain associated with folding. However, much more information on rheology and kinematics can potentially be extracted from fold geometries (Llorens et al., 2013a). We can study the development of folds, quantify the relationships between the different parameters that determine their geometries and estimate their mechanical evolution. This approach allows us to better understand and predict not only rock but also ice deformation. One of the main parameters in fold development is the viscosity contrast between the folding layer and the matrix in which it is embedded (m), since it determines the initial fold wavelength and the amplification rate of the developing folds. Moreover, non-linear viscous rheology influences fold geometry too (Llorens et al., 2013b). We present a series of 2-dimensional simulations of folding of viscous single layers in pure and simple shear. We vary different parameters in order to compare and determine their influence on the resulting fold patterns and the associated mechanical response of the material. To perform these simulations we use the software platform ELLE (www.elle.ws) with the non-linear viscous finite element code BASIL. The results show that layers thicken at the beginning of deformation in all simulations, and visible folds start earlier or later depending on the viscosity contrast. When folds start to nucleate the layer maximum shear strain decreases, moving away from the theoretical trend for homogeneous strain (no folding). This allows the accurate determination of the onset of folding. Maximum deviatoric stresses are higher in power-law than in linear-viscosity materials, and it is initially double in pure shear than in simple shear conditions. Therefore, folding a competent layer requires less work in simple than in pure shear. The maximum deviatoric stress difference between pure and simple shear is less pronounced in power-law materials. It also depends on the original orientation of the layer relative to the shear plane, being the shortening rate initially relatively low when the layer makes a low angle with the shear plane. The mechanical behaviour is similar in pure and simple shear when the layer is oriented at a relative high angle (45°). M-G Llorens, PD Bons, A Griera and E Gomez-Rivas (2013a) When do folds unfold during progressive shear?. Geology, 41, 563-566. M-G Llorens, PD Bons, A Griera, E Gomez-Rivas and LA Evans (2013b) Single layer folding in simple shear. Journal of Structural Geology, 50, 209-220.

Realization of preconditioned Lanczos and conjugate gradient algorithms on optical linear algebra processors.

PubMed

Ghosh, A

1988-08-01

Lanczos and conjugate gradient algorithms are important in computational linear algebra. In this paper, a parallel pipelined realization of these algorithms on a ring of optical linear algebra processors is described. The flow of data is designed to minimize the idle times of the optical multiprocessor and the redundancy of computations. The effects of optical round-off errors on the solutions obtained by the optical Lanczos and conjugate gradient algorithms are analyzed, and it is shown that optical preconditioning can improve the accuracy of these algorithms substantially. Algorithms for optical preconditioning and results of numerical experiments on solving linear systems of equations arising from partial differential equations are discussed. Since the Lanczos algorithm is used mostly with sparse matrices, a folded storage scheme to represent sparse matrices on spatial light modulators is also described.

Mechanical monolithic compact sensors for real-time linear and angular broadband low frequency monitoring and control of spacecrafts and satellites

NASA Astrophysics Data System (ADS)

Barone, F.; Giordano, G.

2017-09-01

In this paper we describe the characteristics and performances of a monolithic sensor designed for low frequency motion measurement of spacecrafts and satellites, whose mechanics is based on the UNISA Folded Pendulum. The latter, developed for ground-based applications, exhibits unique features (compactness, lightness, scalability, low resonance frequency and high quality factor), consequence of the action of the gravitational force on its inertial mass. In this paper we introduce and discuss the general methodology used to extend the application of ground-based folded pendulums to space, also in total absence of gravity, still keeping all their peculiar features and characteristics.

Theory of the Protein Equilibrium Population Snapshot by H/D Exchange Electrospray Ionization Mass Spectrometry (PEPS-HDX-ESI-MS) Method used to obtain Protein Folding Energies/Rates and Selected Supporting Experimental Evidence.

PubMed

Liyanage, Rohana; Devarapalli, Nagarjuna; Pyland, Derek B; Puckett, Latisha M; Phan, N H; Starch, Joel A; Okimoto, Mark R; Gidden, Jennifer; Stites, Wesley E; Lay, Jackson O

2012-12-15

Protein equilibrium snapshot by hydrogen/deuterium exchange electrospray ionization mass spectrometry (PEPS-HDX-ESI-MS or PEPS) is a method recently introduced for estimating protein folding energies and rates. Herein we describe the basis for this method using both theory and new experiments. Benchmark experiments were conducted using ubiquitin because of the availability of reference data for folding and unfolding rates from NMR studies. A second set of experiments was also conducted to illustrate the surprising resilience of the PEPS to changes in HDX time, using staphylococcal nuclease and time frames ranging from a few seconds to several minutes. Theory suggests that PEPS experiments should be conducted at relatively high denaturant concentrations, where the protein folding/unfolding rates are slow with respect to HDX and the life times of both the closed and open states are long enough to be sampled experimentally. Upon deliberate denaturation, changes in folding/unfolding are correlated with associated changes in the ESI-MS signal upon fast HDX. When experiments are done quickly, typically within a few seconds, ESI-MS signals, corresponding to the equilibrium population of the native (closed) and denatured (open) states can both be detected. The interior of folded proteins remains largely un-exchanged. Amongst MS methods, the simultaneous detection of both states in the spectrum is unique to PEPS and provides a "snapshot" of these populations. The associated ion intensities are used to estimate the protein folding equilibrium constant (or the free energy change, ΔG). Linear extrapolation method (LEM) plots of derived ΔG values for each denaturant concentration can then be used to calculate ΔG in the absence of denaturant, ΔG(H(2)O). In accordance with the requirement for detection of signals for both the folded and unfolded states, this theoretical framework predicts that PEPS experiments work best at the middle of the denaturation curve where natured and denatured protein molecules are equilibrated at easily detectable ratios, namely 1:1. It also requires that closed and open states have lifetimes measurable in the time frame of the HDX experiment. Because both conditions are met by PEPS, these measurements can provide an accurate assessment of closed/open state populations and thus protein folding energies/rates.

Determinants of stunting and poor linear growth in children under 2 years of age in India: an in-depth analysis of Maharashtra's comprehensive nutrition survey.

PubMed

Aguayo, Víctor M; Nair, Rajilakshmi; Badgaiyan, Nina; Krishna, Vandana

2016-05-01

We use a representative sample of 2561 children 0-23 months old to identify the factors most significantly associated with child stunting in the state of Maharashtra, India. We find that 22.7% of children were stunted, with one-third (7.4%) of the stunted children severely stunted. Multivariate regression analyses indicate that children born with low birthweight had a 2.5-fold higher odds of being stunted [odds ratio (OR) 2.49; 95% confidence interval (CI) 1.96-3.27]; children 6-23 months old who were not fed a minimum number of times/day had a 63% higher odds of being stunted (OR 1.63; 95% CI 1.24-2.14); and lower consumption of eggs was associated with a two-fold increased odds of stunting in children 6-23 months old (OR 2.07; 95% CI 1.19-3.61); children whose mother's height was < 145 cm, had two-fold higher odds of being stunted (OR 2.04; 95% CI 1.46-2.81); lastly, children of households without access to improved sanitation had 88% higher odds of being severely stunted (OR 1.88; 95% CI 1.17-3.02). Attained linear growth (height-for-age z-score) was significantly lower in children from households without access to improved sanitation, children of mothers without access to electronic media, without decision making power regarding food or whose height was < 145 cm, children born with a low birthweight and children 6-23 months old who were not fed dairy products, fruits and vegetables. In Maharashtra children's birthweight and feeding practices, women's nutrition and status and household sanitation and poverty are the most significant predictors of stunting and poor linear growth in children under 2 years. Key messages One in five (22.7%) of children 0-23 months old in the state of Maharashtra were stunted, and one-third (7.4%) of the stunted children were severely stunted. Birthweight, child feeding, women's nutrition and household sanitation were the most significant predictors of stunting and poor linear growth in children under 2 years. Children born to mothers whose height was below 145 cm, had two-fold higher odds of being stunted; children born with a low birthweight had a 2.5-fold higher odds of being stunted. Low feeding frequency and low consumption of eggs, dairy products, fruits and vegetables were associated with stunting and poor linear growth in children 6-23 months old. Children of households without access to improved sanitation had 88% higher odds of being severely stunted. © 2016 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.

Measurements of vocal fold tissue viscoelasticity: Approaching the male phonatory frequency range

NASA Astrophysics Data System (ADS)

Chan, Roger W.

2004-06-01

Viscoelastic shear properties of human vocal fold tissues have been reported previously. However, data have only been obtained at very low frequencies (<=15 Hz). This necessitates data extrapolation to the frequency range of phonation based on constitutive modeling and time-temperature superposition. This study attempted to obtain empirical measurements at higher frequencies with the use of a controlled strain torsional rheometer, with a design of directly controlling input strain that introduced significantly smaller system inertial errors compared to controlled stress rheometry. Linear viscoelastic shear properties of the vocal fold mucosa (cover) from 17 canine larynges were quantified at frequencies of up to 50 Hz. Consistent with previous data, results showed that the elastic shear modulus (G'), viscous shear modulus (G''), and damping ratio (ζ) of the vocal fold mucosa were relatively constant across 0.016-50 Hz, whereas the dynamic viscosity (ɛ') decreased monotonically with frequency. Constitutive characterization of the empirical data by a quasilinear viscoelastic model and a statistical network model demonstrated trends of viscoelastic behavior at higher frequencies generally following those observed at lower frequencies. These findings supported the use of controlled strain rheometry for future investigations of the viscoelasticity of vocal fold tissues and phonosurgical biomaterials at phonatory frequencies.

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.

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

Plasmon-Enhanced Photocleaving Dynamics in Colloidal MicroRNA-Functionalized Silver Nanoparticles Monitored with Second Harmonic Generation.

PubMed

Kumal, Raju R; Abu-Laban, Mohammad; Landry, Corey R; Kruger, Blake; Zhang, Zhenyu; Hayes, Daniel J; Haber, Louis H

2016-10-11

The photocleaving dynamics of colloidal microRNA-functionalized nanoparticles are studied using time-dependent second harmonic generation (SHG) measurements. Model drug-delivery systems composed of oligonucleotides attached to either silver nanoparticles or polystyrene nanoparticles using a nitrobenzyl photocleavable linker are prepared and characterized. The photoactivated controlled release is observed to be most efficient on resonance at 365 nm irradiation, with pseudo-first-order rate constants that are linearly proportional to irradiation powers. Additionally, silver nanoparticles show a 6-fold plasmon enhancement in photocleaving efficiency over corresponding polystyrene nanoparticle rates, while our previous measurements on gold nanoparticles show a 2-fold plasmon enhancement compared to polystyrene nanoparticles. Characterizations including extinction spectroscopy, electrophoretic mobility, and fluorimetry measurements confirm the analysis from the SHG results. The real-time SHG measurements are shown to be a highly sensitive method for investigating plasmon-enhanced photocleaving dynamics in model drug delivery systems.

Microbial detection method based on sensing molecular hydrogen

NASA Technical Reports Server (NTRS)

Wilkins, J. R.; Stoner, G. E.; Boykin, E. H.

1974-01-01

A simple method for detecting bacteria, based on the time of hydrogen evolution, was developed and tested against various members of the Enterobacteriaceae group. The test system consisted of (1) two electrodes, platinum and a reference electrode, (2) a buffer amplifier, and (3) a strip-chart recorder. Hydrogen evolution was measured by an increase in voltage in the negative (cathodic) direction. A linear relationship was established between inoculum size and the time hydrogen was detected (lag period). Lag times ranged from 1 h for 1 million cells/ml to 7 h for 1 cell/ml. For each 10-fold decrease in inoculum, length of the lag period increased 60 to 70 min. Based on the linear relationship between inoculum and lag period, these results indicate the potential application of the hydrogen-sensing method for rapidly detecting coliforms and other gas-producing microorganisms in a variety of clinical, food, and other samples.

Collapse kinetics and chevron plots from simulations of denaturant-dependent folding of globular proteins

PubMed Central

Liu, Zhenxing; Reddy, Govardhan; O’Brien, Edward P.; Thirumalai, D.

2011-01-01

Quantitative description of how proteins fold under experimental conditions remains a challenging problem. Experiments often use urea and guanidinium chloride to study folding whereas the natural variable in simulations is temperature. To bridge the gap, we use the molecular transfer model that combines measured denaturant-dependent transfer free energies for the peptide group and amino acid residues, and a coarse-grained Cα-side chain model for polypeptide chains to simulate the folding of src SH3 domain. Stability of the native state decreases linearly as [C] (the concentration of guanidinium chloride) increases with the slope, m, that is in excellent agreement with experiments. Remarkably, the calculated folding rate at [C] = 0 is only 16-fold larger than the measured value. Most importantly ln kobs (kobs is the sum of folding and unfolding rates) as a function of [C] has the characteristic V (chevron) shape. In every folding trajectory, the times for reaching the native state, interactions stabilizing all the substructures, and global collapse coincide. The value of (mf is the slope of the folding arm of the chevron plot) is identical to the fraction of buried solvent accessible surface area in the structures of the transition state ensemble. In the dominant transition state, which does not vary significantly at low [C], the core of the protein and certain loops are structured. Besides solving the long-standing problem of computing the chevron plot, our work lays the foundation for incorporating denaturant effects in a physically transparent manner either in all-atom or coarse-grained simulations. PMID:21512127

Collapse kinetics and chevron plots from simulations of denaturant-dependent folding of globular proteins.

PubMed

Liu, Zhenxing; Reddy, Govardhan; O'Brien, Edward P; Thirumalai, D

2011-05-10

Quantitative description of how proteins fold under experimental conditions remains a challenging problem. Experiments often use urea and guanidinium chloride to study folding whereas the natural variable in simulations is temperature. To bridge the gap, we use the molecular transfer model that combines measured denaturant-dependent transfer free energies for the peptide group and amino acid residues, and a coarse-grained C(α)-side chain model for polypeptide chains to simulate the folding of src SH(3) domain. Stability of the native state decreases linearly as [C] (the concentration of guanidinium chloride) increases with the slope, m, that is in excellent agreement with experiments. Remarkably, the calculated folding rate at [C] = 0 is only 16-fold larger than the measured value. Most importantly ln k(obs) (k(obs) is the sum of folding and unfolding rates) as a function of [C] has the characteristic V (chevron) shape. In every folding trajectory, the times for reaching the native state, interactions stabilizing all the substructures, and global collapse coincide. The value of (m(f) is the slope of the folding arm of the chevron plot) is identical to the fraction of buried solvent accessible surface area in the structures of the transition state ensemble. In the dominant transition state, which does not vary significantly at low [C], the core of the protein and certain loops are structured. Besides solving the long-standing problem of computing the chevron plot, our work lays the foundation for incorporating denaturant effects in a physically transparent manner either in all-atom or coarse-grained simulations.

What my dogs forced me to learn about thermal energy transfer

NASA Astrophysics Data System (ADS)

Bohren, Craig F.

2015-05-01

Some objects feel colder to the touch than others at the same (room) temperature. But explaining why by linear, single-factor reasoning is inadequate because the time-dependent thermal energy transfer at solid interfaces initially at different temperatures is determined by the thermal inertia √{ k ρ c } , a function of three thermophysical properties: thermal conductivity k, density ρ, and specific heat capacity per unit mass c. In time-dependent problems 1 / √{ k ρ c } plays the role of a resistance. As an example, although the thermal conductivity of aluminum is 16 times that of stainless steel, this does not translate into a 16-fold difference in interfacial thermal energy flux densities. Nor does it result in a markedly greater perceived coldness of aluminum; the difference is barely perceptible. Similarly, despite the 600-fold difference in the thermal conductivity of iron relative to that of wood, the ratio of thermal energy flux densities is only about 4.6.

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.

Branches of Triangulated Origami Near the Unfolded State

NASA Astrophysics Data System (ADS)

Chen, Bryan Gin-ge; Santangelo, Christian D.

2018-01-01

Origami structures are characterized by a network of folds and vertices joining unbendable plates. For applications to mechanical design and self-folding structures, it is essential to understand the interplay between the set of folds in the unfolded origami and the possible 3D folded configurations. When deforming a structure that has been folded, one can often linearize the geometric constraints, but the degeneracy of the unfolded state makes a linear approach impossible there. We derive a theory for the second-order infinitesimal rigidity of an initially unfolded triangulated origami structure and use it to study the set of nearly unfolded configurations of origami with four boundary vertices. We find that locally, this set consists of a number of distinct "branches" which intersect at the unfolded state, and that the number of these branches is exponential in the number of vertices. We find numerical and analytical evidence that suggests that the branches are characterized by choosing each internal vertex to either "pop up" or "pop down." The large number of pathways along which one can fold an initially unfolded origami structure strongly indicates that a generic structure is likely to become trapped in a "misfolded" state. Thus, new techniques for creating self-folding origami are likely necessary; controlling the popping state of the vertices may be one possibility.

Quantitative Study of the Effects of Dehydration on the Viscoelastic Parameters in the Vocal Fold Mucosa.

PubMed

Yang, Shuai; Zhang, Yu; Mills, Randal D; Jiang, Jack J

2017-05-01

The goal of this study was to quantify the viscoelastic parameters of the vocal fold mucosa at varying dehydration levels. Healthy canine larynges were obtained postmortem, and the samples were separated from the subglottal wall. The samples were dehydrated in a vacuum dryer. According to the total dehydration time per sample, dehydration levels were divided into four degrees: 0%, 40%, 60%, and 80%. The stepper was set to stretch the sample to a level of 35% strain at the same rate (0.5 mm/s). Data collection was repeated five times under each dehydration condition. The compression resilience, RC% = S'/S*100%, and the hysteresis area were measured according to the stress-strain curves. The varying properties of the samples under different dehydration levels were investigated by fitting the curves. The area of the hysteresis loops observed in the stress-strain curves increased exponentially with dehydration levels, whereas the RC% decreased linearly. For all curves, low-strain stages can be explained by Hooke's law (σ = E 0 *ε). With increasing levels of dehydration, E 0 was shown to increase, whereas the linear range was shortened. High-strain stages resembled exponential rather than the linear curves. And the nonlinear stage of the curve became increasingly apparent in the stress-strain curves of increased dehydration levels. The quantitative results in this study not only provide a numerical reference for future experimental measurements, but also can be used to verify the biphasic model in future studies. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Output-only modal parameter estimator of linear time-varying structural systems based on vector TAR model and least squares support vector machine

NASA Astrophysics Data System (ADS)

Zhou, Si-Da; Ma, Yuan-Chen; Liu, Li; Kang, Jie; Ma, Zhi-Sai; Yu, Lei

2018-01-01

Identification of time-varying modal parameters contributes to the structural health monitoring, fault detection, vibration control, etc. of the operational time-varying structural systems. However, it is a challenging task because there is not more information for the identification of the time-varying systems than that of the time-invariant systems. This paper presents a vector time-dependent autoregressive model and least squares support vector machine based modal parameter estimator for linear time-varying structural systems in case of output-only measurements. To reduce the computational cost, a Wendland's compactly supported radial basis function is used to achieve the sparsity of the Gram matrix. A Gamma-test-based non-parametric approach of selecting the regularization factor is adapted for the proposed estimator to replace the time-consuming n-fold cross validation. A series of numerical examples have illustrated the advantages of the proposed modal parameter estimator on the suppression of the overestimate and the short data. A laboratory experiment has further validated the proposed estimator.

Protein Folding Free Energy Landscape along the Committor - the Optimal Folding Coordinate.

PubMed

Krivov, Sergei V

2018-06-06

Recent advances in simulation and experiment have led to dramatic increases in the quantity and complexity of produced data, which makes the development of automated analysis tools very important. A powerful approach to analyze dynamics contained in such data sets is to describe/approximate it by diffusion on a free energy landscape - free energy as a function of reaction coordinates (RC). For the description to be quantitatively accurate, RCs should be chosen in an optimal way. Recent theoretical results show that such an optimal RC exists; however, determining it for practical systems is a very difficult unsolved problem. Here we describe a solution to this problem. We describe an adaptive nonparametric approach to accurately determine the optimal RC (the committor) for an equilibrium trajectory of a realistic system. In contrast to alternative approaches, which require a functional form with many parameters to approximate an RC and thus extensive expertise with the system, the suggested approach is nonparametric and can approximate any RC with high accuracy without system specific information. To avoid overfitting for a realistically sampled system, the approach performs RC optimization in an adaptive manner by focusing optimization on less optimized spatiotemporal regions of the RC. The power of the approach is illustrated on a long equilibrium atomistic folding simulation of HP35 protein. We have determined the optimal folding RC - the committor, which was confirmed by passing a stringent committor validation test. It allowed us to determine a first quantitatively accurate protein folding free energy landscape. We have confirmed the recent theoretical results that diffusion on such a free energy profile can be used to compute exactly the equilibrium flux, the mean first passage times, and the mean transition path times between any two points on the profile. We have shown that the mean squared displacement along the optimal RC grows linear with time as for simple diffusion. The free energy profile allowed us to obtain a direct rigorous estimate of the pre-exponential factor for the folding dynamics.

The mechanics of fault-bend folding and tear-fault systems in the Niger Delta

NASA Astrophysics Data System (ADS)

Benesh, Nathan Philip

This dissertation investigates the mechanics of fault-bend folding using the discrete element method (DEM) and explores the nature of tear-fault systems in the deep-water Niger Delta fold-and-thrust belt. In Chapter 1, we employ the DEM to investigate the development of growth structures in anticlinal fault-bend folds. This work was inspired by observations that growth strata in active folds show a pronounced upward decrease in bed dip, in contrast to traditional kinematic fault-bend fold models. Our analysis shows that the modeled folds grow largely by parallel folding as specified by the kinematic theory; however, the process of folding over a broad axial surface zone yields a component of fold growth by limb rotation that is consistent with the patterns observed in natural folds. This result has important implications for how growth structures can he used to constrain slip and paleo-earthquake ages on active blind-thrust faults. In Chapter 2, we expand our DEM study to investigate the development of a wider range of fault-bend folds. We examine the influence of mechanical stratigraphy and quantitatively compare our models with the relationships between fold and fault shape prescribed by the kinematic theory. While the synclinal fault-bend models closely match the kinematic theory, the modeled anticlinal fault-bend folds show robust behavior that is distinct from the kinematic theory. Specifically, we observe that modeled structures maintain a linear relationship between fold shape (gamma) and fault-horizon cutoff angle (theta), rather than expressing the non-linear relationship with two distinct modes of anticlinal folding that is prescribed by the kinematic theory. These observations lead to a revised quantitative relationship for fault-bend folds that can serve as a useful interpretation tool. Finally, in Chapter 3, we examine the 3D relationships of tear- and thrust-fault systems in the western, deep-water Niger Delta. Using 3D seismic reflection data and new map-based structural restoration techniques, we find that the tear faults have distinct displacement patterns that distinguish them from conventional strike-slip faults and reflect their roles in accommodating displacement gradients within the fold-and-thrust belt.

Structural development of high-temperature mylonites in the Archean Wyoming province, northwestern Madison Range, Montana

USGS Publications Warehouse

Kellogg, Karl S.; Mogk, David W.

2009-01-01

The Crooked Creek mylonite, in the northwestern Madison Range, southwestern Montana, is defined by several curved lenses of high non-coaxial strain exposed over a 7-km-wide, northeast-trending strip. The country rocks, part of the Archean Wyoming province, are dominantly trondhjemitic to granitic orthogneiss with subordinate amphibolite, quartzite, aluminous gneiss, and sills of metabasite (mafic granulite). Data presented here support an interpretation that the mylonite formed during a period of rapid, heterogeneous strain at near-peak metamorphic conditions during an early deformational event (D1) caused by northwest–southeast-directed transpression. The mylonite has a well-developed L-S tectonite fabric and a fine-grained, recrystallized (granoblastic) texture. The strong linear fabric, interpreted as the stretching direction, is defined by elongate compositional “fish,” fold axes, aligned elongate minerals, and mullion axes. The margins of the mylonitic zones are concordant with and grade into regions of unmylonitized gneiss. A second deformational event (D2) has folded the mylonite surface to produce meter- to kilometer-scale, tight-to-isoclinal, gently plunging folds in both the mylonite and country rock, and represents a northwest–southeast shortening event. Planar or linear fabrics associated with D2 are remarkably absent. A third regional deformational event (D3) produced open, kilometer-scale folds generally with gently north-plunging fold axes. Thermobarometric measurements presented here indicate that metamorphic conditions during D1 were the same in both the mylonite and the country gneiss, reaching upper amphibolite- to lower granulite-facies conditions: 700 ± 50° C and 8.5 ± 0.5 kb. Previous geochronological studies of mylonitic and cross-cutting rocks in the Jerome Rock Lake area, east of the Crooked Creek mylonite, bracket the timing of this high-grade metamorphism and mylonitization between 2.78 and 2.56 Ga, nearly a billion years before the 1.78-Ga Big Sky orogeny, which overprinted the basement rocks exposed in adjacent ranges of the Wyoming province.

Multicenter evaluation of the performance characteristics of the bayer VERSANT HCV RNA 3.0 assay (bDNA).

PubMed

Elbeik, Tarek; Surtihadi, Johan; Destree, Mark; Gorlin, Jed; Holodniy, Mark; Jortani, Saeed A; Kuramoto, Ken; Ng, Valerie; Valdes, Roland; Valsamakis, Alexandra; Terrault, Norah A

2004-02-01

In this multicenter evaluation, the VERSANT HCV RNA 3.0 Assay (bDNA) (Bayer Diagnostics, Tarrytown, N.Y.) was shown to have excellent reproducibility, linearity, and analytical sensitivity across specimen collection matrices (serum, EDTA, ACD-A), and hepatitis C virus (HCV) genotypes 1 to 6. The VERSANT HCV bDNA Assay has a reportable range of 615 to 7690000 (7.69 x 10(6)) IU/ml. The total coefficient of variation (CV) ranged from 32.4% at 615 IU/ml to 17% at 6.8 x 10(6) IU/ml. The assay was linear across the reportable range. Analytical specificity of 98.8% was determined by testing 999 specimens from volunteer blood donors. Evaluation of HCV genotypes using RNA transcripts of representative clones of 1a, 1b, 2a, 2b, 2c, 3a, 4a, 5a, and 6a and patient specimens showed that the largest difference between genotype 1, upon which the assay is standardized, and non-1 genotypes was within 1.5-fold. Testing of potentially interfering endogenous substances and exogenous substances and conditions found no interference in HCV-positive or HCV-negative specimens except for unconjugated bilirubin at concentrations of >or=20 mg/dl and protein at concentrations of >or=9 g/dl. Biological variability was estimated from 29 clinically stable individuals not on HCV therapy who were tested weekly over an 8-week period. The combined estimate of total (biologic plus assay) variability was 0.15 log(10) standard deviation (CV, 36.1%), a fold change of 2.6. Thus, the observed fold change between any two consecutive HCV RNA measures is expected to be less than 2.6-fold (equivalent to 0.41 log(10) IU/ml) 95% of the time in clinically stable individuals.

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

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.

Multidisciplinary Biomarkers of Early Mammary Carcinogenesis

DTIC Science & Technology

2011-04-01

cDNA prepared. Quantitative real-time PCR (qRT-PCR) was then performed on the cDNA. All qRT-PCR reactions were performed in triplicate. ESR1 ...in Figure 4, all ER(+) cells express ESR1 at high levels (at least 4 fold higher than ER(-) cell lines). A Pearson correlation coefficient was...calculated to determine the linear relationship between the optical redox ratio and ESR1 expression levels and found to be significant (p = 0.0024, r

Wrinkle-to-fold transition in soft layers under equi-biaxial strain: A weakly nonlinear analysis

NASA Astrophysics Data System (ADS)

Ciarletta, P.

2014-12-01

Soft materials can experience a mechanical instability when subjected to a finite compression, developing wrinkles which may eventually evolve into folds or creases. The possibility to control the wrinkling network morphology has recently found several applications in many developing fields, such as scaffolds for biomaterials, stretchable electronics and surface micro-fabrication. Albeit much is known of the pattern initiation at the linear stability order, the nonlinear effects driving the pattern selection in soft materials are still unknown. This work aims at investigating the nature of the elastic bifurcation undertaken by a growing soft layer subjected to a equi-biaxial strain. Considering a skin effect at the free surface, the instability thresholds are found to be controlled by a characteristic length, defined by the ratio between capillary energy and bulk elasticity. For the first time, a weakly nonlinear analysis of the wrinkling instability is performed here using the multiple-scale perturbation method applied to the incremental theory in finite elasticity. The Ginzburg-Landau equations are derived for different superposing linear modes. This study proves that a subcritical pitchfork bifurcation drives the observed wrinkle-to-fold transition in swelling gels experiments, favoring the emergence of hexagonal creased patterns, albeit quasi-hexagonal patterns might later emerge because of an expected symmetry break. Moreover, if the surface energy is somewhat comparable to the bulk elastic energy, it has the same stabilizing effect as for fluid instabilities, driving the formation of stable wrinkles, as observed in elastic bi-layered materials.

Influence of rice straw cooking conditions in the soda-ethanol-water pulping on the mechanical properties of produced paper sheets.

PubMed

Navaee-Ardeh, S; Mohammadi-Rovshandeh, J; Pourjoozi, M

2004-03-01

A normalized design was used to examine the influence of independent variables (alcohol concentration, cooking time and temperature) in the catalytic soda-ethanol pulping of rice straw on various mechanical properties (breaking length, burst, tear index and folding endurance) of paper sheets obtained from each pulping process. An equation of each dependent variable as a function of cooking variables (independent variables) was obtained by multiple non-linear regression using the least square method by MATLAB software for developing of empirical models. The ranges of alcohol concentration, cooking time and temperature were 40-65% (w/w), 150-180 min and 195-210 degrees C, respectively. Three-dimensional graphs of dependent variables were also plotted versus independent variables. The optimum values of breaking length, burst and tear index and folding endurance were 4683.7 (m), 30.99 (kN/g), 376.93 (mN m2/g) and 27.31, respectively. However, short cooking time (150 min), high ethanol concentration (65%) and high temperature (210 degrees C) could be used to produce papers with suitable burst and tear index. However, for papers with best breaking length and folding endurance low temperature (195 degrees C) was desirable. Differences between optimum values of dependent variables obtained by normalized design and experimental data were less than 20%.

Time-on-task decrements in "steer clear" performance of patients with sleep apnea and narcolepsy

NASA Technical Reports Server (NTRS)

Findley, L. J.; Suratt, P. M.; Dinges, D. F.

1999-01-01

Loss of attention with time-on-task reflects the increasing instability of the waking state during performance in experimentally induced sleepiness. To determine whether patients with disorders of excessive sleepiness also displayed time-on-task decrements indicative of wake state instability, visual sustained attention performance on "Steer Clear," a computerized simple RT driving simulation task, was compared among 31 patients with untreated sleep apnea, 16 patients with narcolepsy, and 14 healthy control subjects. Vigilance decrement functions were generated by analyzing the number of collisions in each of six four-minute periods of Steer Clear task performance in a mixed-model analysis of variance and linear regression equations. As expected, patients had more Steer Clear collisions than control subjects (p=0.006). However, the inter-subject variability in errors among the narcoleptic patients was four-fold that of the apnea patients, and 100-fold that of the controls volunteers; the variance in errors among untreated apnea patients was 27-times that of controls. The results of transformed collision data revealed main effects for group (p=0.006), time-on-task (p=0.001), and a significant interaction (p=0.022). Control subjects showed no clear evidence of increasing collision errors with time-on-task (adjusted R2=0.22), while apnea patients showed a trend toward vigilance decrement (adjusted R2=0.42, p=0.097), and narcolepsy patients evidenced a robust linear vigilance decrement (adjusted R2=0.87, p=0.004). The association of disorders of excessive somnolence with escalating time-on-task decrements makes it imperative that when assessment of neurobehavioral performance is conducted in patients, it involves task durations and analyses that will evaluate the underlying vulnerability of potentially sleepy patients to decrements over time in tasks that require sustained attention and timely responses, both of which are key components in safe driving performance.

A phase transition in energy-filtered RNA secondary structures.

PubMed

Han, Hillary S W; Reidys, Christian M

2012-10-01

In this article we study the effect of energy parameters on minimum free energy (mfe) RNA secondary structures. Employing a simplified combinatorial energy model that is only dependent on the diagram representation and is not sequence-specific, we prove the following dichotomy result. Mfe structures derived via the Turner energy parameters contain only finitely many complex irreducible substructures, and just minor parameter changes produce a class of mfe structures that contain a large number of small irreducibles. We localize the exact point at which the distribution of irreducibles experiences this phase transition from a discrete limit to a central limit distribution and, subsequently, put our result into the context of quantifying the effect of sparsification of the folding of these respective mfe structures. We show that the sparsification of realistic mfe structures leads to a constant time and space reduction, and that the sparsification of the folding of structures with modified parameters leads to a linear time and space reduction. We, furthermore, identify the limit distribution at the phase transition as a Rayleigh distribution.

Using linear algebra for protein structural comparison and classification

PubMed Central

2009-01-01

In this article, we describe a novel methodology to extract semantic characteristics from protein structures using linear algebra in order to compose structural signature vectors which may be used efficiently to compare and classify protein structures into fold families. These signatures are built from the pattern of hydrophobic intrachain interactions using Singular Value Decomposition (SVD) and Latent Semantic Indexing (LSI) techniques. Considering proteins as documents and contacts as terms, we have built a retrieval system which is able to find conserved contacts in samples of myoglobin fold family and to retrieve these proteins among proteins of varied folds with precision of up to 80%. The classifier is a web tool available at our laboratory website. Users can search for similar chains from a specific PDB, view and compare their contact maps and browse their structures using a JMol plug-in. PMID:21637532

Using linear algebra for protein structural comparison and classification.

PubMed

Gomide, Janaína; Melo-Minardi, Raquel; Dos Santos, Marcos Augusto; Neshich, Goran; Meira, Wagner; Lopes, Júlio César; Santoro, Marcelo

2009-07-01

In this article, we describe a novel methodology to extract semantic characteristics from protein structures using linear algebra in order to compose structural signature vectors which may be used efficiently to compare and classify protein structures into fold families. These signatures are built from the pattern of hydrophobic intrachain interactions using Singular Value Decomposition (SVD) and Latent Semantic Indexing (LSI) techniques. Considering proteins as documents and contacts as terms, we have built a retrieval system which is able to find conserved contacts in samples of myoglobin fold family and to retrieve these proteins among proteins of varied folds with precision of up to 80%. The classifier is a web tool available at our laboratory website. Users can search for similar chains from a specific PDB, view and compare their contact maps and browse their structures using a JMol plug-in.

The electrical response of turtle cones to flashes and steps of light.

PubMed

Baylor, D A; Hodgkin, A L; Lamb, T D

1974-11-01

1. The linear response of turtle cones to weak flashes or steps of light was usually well fitted by equations based on a chain of six or seven reactions with time constants varying over about a 6-fold range.2. The temperature coefficient (Q(10)) of the reciprocal of the time to peak of the response to a flash was 1.8 (15-25 degrees C), corresponding to an activation energy of 10 kcal/mole.3. Electrical measurements with one internal electrode and a balancing circuit gave the following results on red-sensitive cones of high resistance: resistance across cell surface in dark 50-170 MOmega; time constant in dark 4-6.5 msec. The effect of a bright light was to increase the resistance and time constant by 10-30%.4. If the cell time constant, resting potential and maximum hyperpolarization are known, the fraction of ionic channels blocked by light at any instant can be calculated from the hyperpolarization and its rate of change. At times less than 50 msec the shape of this relation is consistent with the idea that the concentration of a blocking molecule which varies linearly with light intensity is in equilibrium with the fraction of ionic channels blocked.5. The rising phase of the response to flashes and steps of light covering a 10(5)-fold range of intensities is well fitted by a theory in which the essential assumptions are that (i) light starts a linear chain of reactions leading to the production of a substance which blocks ionic channels in the outer segment, (ii) an equilibrium between the blocking molecules and unblocked channels is established rapidly, and (iii) the electrical properties of the cell can be represented by a simple circuit with a time constant in the dark of about 6 msec.6. Deviations from the simple theory which occur after 50 msec are attributed partly to a time-dependent desensitization mechanism and partly to a change in saturation potential resulting from a voltage-dependent change in conductance.7. The existence of several components in the relaxation of the potential to its resting level can be explained by supposing that the ;substance' which blocks light sensitive ionic channels is inactivated in a series of steps.

Anytime query-tuned kernel machine classifiers via Cholesky factorization

NASA Technical Reports Server (NTRS)

DeCoste, D.

2002-01-01

We recently demonstrated 2 to 64-fold query-time speedups of Support Vector Machine and Kernel Fisher classifiers via a new computational geometry method for anytime output bounds (DeCoste,2002). This new paper refines our approach in two key ways. First, we introduce a simple linear algebra formulation based on Cholesky factorization, yielding simpler equations and lower computational overhead. Second, this new formulation suggests new methods for achieving additional speedups, including tuning on query samples. We demonstrate effectiveness on benchmark datasets.

New Protein Mimetics: The Zinc Finger Motif as a Locked-In Tertiary Fold.

PubMed

Tuchscherer, Gabriele; Lehmann, Christian; Mathieu, Marc

1998-11-16

The principle of a molecular kit is used for the covalent assembly of secondary structure forming peptide blocks to predetermined packing topologies. The resulting locked-in folds (LIFs; depicted schematically) are readily accessible and bypass the intriguing folding problem of linear peptide chains. This strategy allows, for example, mimicking of the essential structural and functional features of zinc finger proteins. © 1998 WILEY-VCH Verlag GmbH, Weinheim, Fed. Rep. of Germany.

Normal Unenhanced Raman Spectra of CO and CH/sub 4/ adsorbed on cobalt(poly)

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

Marzouk, H.A.; Bradley, E.B.; Arunkumar, K.A.

Normal Unenhanced Raman Spectra (NURS) of low-polarizability CO molecules were observed for the first time on cobalt at R.T. and residual gas pressure. We assign five bands observed between 2030--2130 cm/sup -1/ to linear chemisorbed CO species, while those observed between 1840--2010 cm/sup -1/ have been ascribed to the 2--fold chemisorbed species. The three bands observed between 1740--1830 cm/sup -1/ we believe are due to the 3--fold species. The corresponding fourteen Co-C stretches were observed and assigned. A model based upon electron backdonation is proposed for each of the three structures. NURS were also observed at R.T. for physisorbed CH/submore » 4/ and assignments are made to the four frequencies of CH/sub 4/.« less

Mechanomimetic hydrogels for vocal fold lamina propria regeneration.

PubMed

Kutty, Jaishankar K; Webb, Ken

2009-01-01

Vocal fold injury commonly leads to reduced vocal quality due to scarring-induced alterations in matrix composition and tissue biomechanics. The long-term hypothesis motivating our work is that rapid restoration of phonation and the associated dynamic mechanical environment will reduce scarring and promote regenerative healing. Toward this end, the objective of this study was to develop mechanomimetic, degradable hydrogels approximating the viscoelastic properties of the vocal ligament and mucosa that may be photopolymerized in situ to restore structural integrity to vocal fold tissues. The tensile and rheological properties of hydrogels (targeting the vocal ligament and mucosa, respectively) were varied as a function of macromer concentration. PEG diacrylate-based hydrogels exhibited linear stress-strain response and elastic modulus consistent with the properties of the vocal ligament at low strains (0-15%), but did not replicate the non-linear behavior observed in native tissue at higher strains. Methacrylated hyaluronic acid hydrogels displayed dynamic viscosity consistent with native vocal mucosa, while elastic shear moduli values were several-fold higher. Cell culture studies indicated that both hydrogels supported spreading, proliferation and collagen/proteoglycan matrix deposition by encapsulated fibroblasts throughout the 3D network.

GLOBAL SOLUTIONS TO FOLDED CONCAVE PENALIZED NONCONVEX LEARNING

PubMed Central

Liu, Hongcheng; Yao, Tao; Li, Runze

2015-01-01

This paper is concerned with solving nonconvex learning problems with folded concave penalty. Despite that their global solutions entail desirable statistical properties, there lack optimization techniques that guarantee global optimality in a general setting. In this paper, we show that a class of nonconvex learning problems are equivalent to general quadratic programs. This equivalence facilitates us in developing mixed integer linear programming reformulations, which admit finite algorithms that find a provably global optimal solution. We refer to this reformulation-based technique as the mixed integer programming-based global optimization (MIPGO). To our knowledge, this is the first global optimization scheme with a theoretical guarantee for folded concave penalized nonconvex learning with the SCAD penalty (Fan and Li, 2001) and the MCP penalty (Zhang, 2010). Numerical results indicate a significant outperformance of MIPGO over the state-of-the-art solution scheme, local linear approximation, and other alternative solution techniques in literature in terms of solution quality. PMID:27141126

RBF kernel based support vector regression to estimate the blood volume and heart rate responses during hemodialysis.

PubMed

Javed, Faizan; Chan, Gregory S H; Savkin, Andrey V; Middleton, Paul M; Malouf, Philip; Steel, Elizabeth; Mackie, James; Lovell, Nigel H

2009-01-01

This paper uses non-linear support vector regression (SVR) to model the blood volume and heart rate (HR) responses in 9 hemodynamically stable kidney failure patients during hemodialysis. Using radial bias function (RBF) kernels the non-parametric models of relative blood volume (RBV) change with time as well as percentage change in HR with respect to RBV were obtained. The e-insensitivity based loss function was used for SVR modeling. Selection of the design parameters which includes capacity (C), insensitivity region (e) and the RBF kernel parameter (sigma) was made based on a grid search approach and the selected models were cross-validated using the average mean square error (AMSE) calculated from testing data based on a k-fold cross-validation technique. Linear regression was also applied to fit the curves and the AMSE was calculated for comparison with SVR. For the model based on RBV with time, SVR gave a lower AMSE for both training (AMSE=1.5) as well as testing data (AMSE=1.4) compared to linear regression (AMSE=1.8 and 1.5). SVR also provided a better fit for HR with RBV for both training as well as testing data (AMSE=15.8 and 16.4) compared to linear regression (AMSE=25.2 and 20.1).

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.

Protein fold recognition using geometric kernel data fusion.

PubMed

Zakeri, Pooya; Jeuris, Ben; Vandebril, Raf; Moreau, Yves

2014-07-01

Various approaches based on features extracted from protein sequences and often machine learning methods have been used in the prediction of protein folds. Finding an efficient technique for integrating these different protein features has received increasing attention. In particular, kernel methods are an interesting class of techniques for integrating heterogeneous data. Various methods have been proposed to fuse multiple kernels. Most techniques for multiple kernel learning focus on learning a convex linear combination of base kernels. In addition to the limitation of linear combinations, working with such approaches could cause a loss of potentially useful information. We design several techniques to combine kernel matrices by taking more involved, geometry inspired means of these matrices instead of convex linear combinations. We consider various sequence-based protein features including information extracted directly from position-specific scoring matrices and local sequence alignment. We evaluate our methods for classification on the SCOP PDB-40D benchmark dataset for protein fold recognition. The best overall accuracy on the protein fold recognition test set obtained by our methods is ∼ 86.7%. This is an improvement over the results of the best existing approach. Moreover, our computational model has been developed by incorporating the functional domain composition of proteins through a hybridization model. It is observed that by using our proposed hybridization model, the protein fold recognition accuracy is further improved to 89.30%. Furthermore, we investigate the performance of our approach on the protein remote homology detection problem by fusing multiple string kernels. The MATLAB code used for our proposed geometric kernel fusion frameworks are publicly available at http://people.cs.kuleuven.be/∼raf.vandebril/homepage/software/geomean.php?menu=5/. © The Author 2014. Published by Oxford University Press.

Numerical solution of fluid-structure interaction represented by human vocal folds in airflow

NASA Astrophysics Data System (ADS)

Valášek, J.; Sváček, P.; Horáček, J.

2016-03-01

The paper deals with the human vocal folds vibration excited by the fluid flow. The vocal fold is modelled as an elastic body assuming small displacements and therefore linear elasticity theory is used. The viscous incompressible fluid flow is considered. For purpose of numerical solution the arbitrary Lagrangian-Euler method (ALE) is used. The whole problem is solved by the finite element method (FEM) based solver. Results of numerical experiments with different boundary conditions are presented.

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.

Limits of linearity and detection for some drugs of abuse.

PubMed

Needleman, S B; Romberg, R W

1990-01-01

The limits of linearity (LOL) and detection (LOD) are important factors in establishing the reliability of an analytical procedure for accurately assaying drug concentrations in urine specimens. Multiple analyses of analyte over an extended range of concentrations provide a measure of the ability of the analytical procedure to correctly identify known quantities of drug in a biofluid matrix. Each of the seven drugs of abuse gives linear analytical responses from concentrations at or near their LOD to concentrations several-fold higher than those generally encountered in the drug screening laboratory. The upper LOL exceeds the Department of Navy (DON) cutoff values by factors of approximately 2 to 160. The LOD varies from 0.4 to 5.0% of the DON cutoff value for each drug. The limit of quantitation (LOQ) is calculated as the LOD + 7 SD. The range for LOL is greater for drugs analyzed with deuterated internal standards compared with those using conventional internal standards. For THC acid, cocaine, PCP, and morphine, LOLs are 8 to 160-fold greater than the defined cutoff concentrations. For the other drugs, the LOL's are only 2 to 4-fold greater than the defined cutoff concentrations.

Strain Modulations as a Mechanism to Reduce Stress Relaxation in Laryngeal Tissues

PubMed Central

Hunter, Eric J.; Siegmund, Thomas; Chan, Roger W.

2014-01-01

Vocal fold tissues in animal and human species undergo deformation processes at several types of loading rates: a slow strain involved in vocal fold posturing (on the order of 1 Hz or so), cyclic and faster posturing often found in speech tasks or vocal embellishment (1–10 Hz), and shear strain associated with vocal fold vibration during phonation (100 Hz and higher). Relevant to these deformation patterns are the viscous properties of laryngeal tissues, which exhibit non-linear stress relaxation and recovery. In the current study, a large strain time-dependent constitutive model of human vocal fold tissue is used to investigate effects of phonatory posturing cyclic strain in the range of 1 Hz to 10 Hz. Tissue data for two subjects are considered and used to contrast the potential effects of age. Results suggest that modulation frequency and extent (amplitude), as well as the amount of vocal fold overall strain, all affect the change in stress relaxation with modulation added. Generally, the vocal fold cover reduces the rate of relaxation while the opposite is true for the vocal ligament. Further, higher modulation frequencies appear to reduce the rate of relaxation, primarily affecting the ligament. The potential benefits of cyclic strain, often found in vibrato (around 5 Hz modulation) and intonational inflection, are discussed in terms of vocal effort and vocal pitch maintenance. Additionally, elderly tissue appears to not exhibit these benefits to modulation. The exacerbating effect such modulations may have on certain voice disorders, such as muscle tension dysphonia, are explored. PMID:24614616

Strain modulations as a mechanism to reduce stress relaxation in laryngeal tissues.

PubMed

Hunter, Eric J; Siegmund, Thomas; Chan, Roger W

2014-01-01

Vocal fold tissues in animal and human species undergo deformation processes at several types of loading rates: a slow strain involved in vocal fold posturing (on the order of 1 Hz or so), cyclic and faster posturing often found in speech tasks or vocal embellishment (1-10 Hz), and shear strain associated with vocal fold vibration during phonation (100 Hz and higher). Relevant to these deformation patterns are the viscous properties of laryngeal tissues, which exhibit non-linear stress relaxation and recovery. In the current study, a large strain time-dependent constitutive model of human vocal fold tissue is used to investigate effects of phonatory posturing cyclic strain in the range of 1 Hz to 10 Hz. Tissue data for two subjects are considered and used to contrast the potential effects of age. Results suggest that modulation frequency and extent (amplitude), as well as the amount of vocal fold overall strain, all affect the change in stress relaxation with modulation added. Generally, the vocal fold cover reduces the rate of relaxation while the opposite is true for the vocal ligament. Further, higher modulation frequencies appear to reduce the rate of relaxation, primarily affecting the ligament. The potential benefits of cyclic strain, often found in vibrato (around 5 Hz modulation) and intonational inflection, are discussed in terms of vocal effort and vocal pitch maintenance. Additionally, elderly tissue appears to not exhibit these benefits to modulation. The exacerbating effect such modulations may have on certain voice disorders, such as muscle tension dysphonia, are explored.

Folded concave penalized sparse linear regression: sparsity, statistical performance, and algorithmic theory for local solutions.

PubMed

Liu, Hongcheng; Yao, Tao; Li, Runze; Ye, Yinyu

2017-11-01

This paper concerns the folded concave penalized sparse linear regression (FCPSLR), a class of popular sparse recovery methods. Although FCPSLR yields desirable recovery performance when solved globally, computing a global solution is NP-complete. Despite some existing statistical performance analyses on local minimizers or on specific FCPSLR-based learning algorithms, it still remains open questions whether local solutions that are known to admit fully polynomial-time approximation schemes (FPTAS) may already be sufficient to ensure the statistical performance, and whether that statistical performance can be non-contingent on the specific designs of computing procedures. To address the questions, this paper presents the following threefold results: (i) Any local solution (stationary point) is a sparse estimator, under some conditions on the parameters of the folded concave penalties. (ii) Perhaps more importantly, any local solution satisfying a significant subspace second-order necessary condition (S 3 ONC), which is weaker than the second-order KKT condition, yields a bounded error in approximating the true parameter with high probability. In addition, if the minimal signal strength is sufficient, the S 3 ONC solution likely recovers the oracle solution. This result also explicates that the goal of improving the statistical performance is consistent with the optimization criteria of minimizing the suboptimality gap in solving the non-convex programming formulation of FCPSLR. (iii) We apply (ii) to the special case of FCPSLR with minimax concave penalty (MCP) and show that under the restricted eigenvalue condition, any S 3 ONC solution with a better objective value than the Lasso solution entails the strong oracle property. In addition, such a solution generates a model error (ME) comparable to the optimal but exponential-time sparse estimator given a sufficient sample size, while the worst-case ME is comparable to the Lasso in general. Furthermore, to guarantee the S 3 ONC admits FPTAS.

Long-time uncertainty propagation using generalized polynomial chaos and flow map composition

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

Luchtenburg, Dirk M., E-mail: dluchten@cooper.edu; Brunton, Steven L.; Rowley, Clarence W.

2014-10-01

We present an efficient and accurate method for long-time uncertainty propagation in dynamical systems. Uncertain initial conditions and parameters are both addressed. The method approximates the intermediate short-time flow maps by spectral polynomial bases, as in the generalized polynomial chaos (gPC) method, and uses flow map composition to construct the long-time flow map. In contrast to the gPC method, this approach has spectral error convergence for both short and long integration times. The short-time flow map is characterized by small stretching and folding of the associated trajectories and hence can be well represented by a relatively low-degree basis. The compositionmore » of these low-degree polynomial bases then accurately describes the uncertainty behavior for long integration times. The key to the method is that the degree of the resulting polynomial approximation increases exponentially in the number of time intervals, while the number of polynomial coefficients either remains constant (for an autonomous system) or increases linearly in the number of time intervals (for a non-autonomous system). The findings are illustrated on several numerical examples including a nonlinear ordinary differential equation (ODE) with an uncertain initial condition, a linear ODE with an uncertain model parameter, and a two-dimensional, non-autonomous double gyre flow.« less

Linear and exponential TAIL-PCR: a method for efficient and quick amplification of flanking sequences adjacent to Tn5 transposon insertion sites.

PubMed

Jia, Xianbo; Lin, Xinjian; Chen, Jichen

2017-11-02

Current genome walking methods are very time consuming, and many produce non-specific amplification products. To amplify the flanking sequences that are adjacent to Tn5 transposon insertion sites in Serratia marcescens FZSF02, we developed a genome walking method based on TAIL-PCR. This PCR method added a 20-cycle linear amplification step before the exponential amplification step to increase the concentration of the target sequences. Products of the linear amplification and the exponential amplification were diluted 100-fold to decrease the concentration of the templates that cause non-specific amplification. Fast DNA polymerase with a high extension speed was used in this method, and an amplification program was used to rapidly amplify long specific sequences. With this linear and exponential TAIL-PCR (LETAIL-PCR), we successfully obtained products larger than 2 kb from Tn5 transposon insertion mutant strains within 3 h. This method can be widely used in genome walking studies to amplify unknown sequences that are adjacent to known sequences.

Multicenter Evaluation of the Performance Characteristics of the Bayer VERSANT HCV RNA 3.0 Assay (bDNA)

PubMed Central

Elbeik, Tarek; Surtihadi, Johan; Destree, Mark; Gorlin, Jed; Holodniy, Mark; Jortani, Saeed A.; Kuramoto, Ken; Ng, Valerie; Valdes, Roland; Valsamakis, Alexandra; Terrault, Norah A.

2004-01-01

In this multicenter evaluation, the VERSANT HCV RNA 3.0 Assay (bDNA) (Bayer Diagnostics, Tarrytown, N.Y.) was shown to have excellent reproducibility, linearity, and analytical sensitivity across specimen collection matrices (serum, EDTA, ACD-A), and hepatitis C virus (HCV) genotypes 1 to 6. The VERSANT HCV bDNA Assay has a reportable range of 615 to 7,690,000 (7.69 × 106) IU/ml. The total coefficient of variation (CV) ranged from 32.4% at 615 IU/ml to 17% at 6.8 × 106 IU/ml. The assay was linear across the reportable range. Analytical specificity of 98.8% was determined by testing 999 specimens from volunteer blood donors. Evaluation of HCV genotypes using RNA transcripts of representative clones of 1a, 1b, 2a, 2b, 2c, 3a, 4a, 5a, and 6a and patient specimens showed that the largest difference between genotype 1, upon which the assay is standardized, and non-1 genotypes was within 1.5-fold. Testing of potentially interfering endogenous substances and exogenous substances and conditions found no interference in HCV-positive or HCV-negative specimens except for unconjugated bilirubin at concentrations of ≥20 mg/dl and protein at concentrations of ≥9 g/dl. Biological variability was estimated from 29 clinically stable individuals not on HCV therapy who were tested weekly over an 8-week period. The combined estimate of total (biologic plus assay) variability was 0.15 log10 standard deviation (CV, 36.1%), a fold change of 2.6. Thus, the observed fold change between any two consecutive HCV RNA measures is expected to be less than 2.6-fold (equivalent to 0.41 log10 IU/ml) 95% of the time in clinically stable individuals. PMID:14766817

Second trimester serum cortisol and preterm birth: an analysis by timing and subtype.

PubMed

Bandoli, Gretchen; Jelliffe-Pawlowski, Laura L; Feuer, Sky K; Liang, Liang; Oltman, Scott P; Paynter, Randi; Ross, Kharah M; Schetter, Christine Dunkel; Ryckman, Kelli K; Chambers, Christina D

2018-05-24

We hypothesized second trimester serum cortisol would be higher in spontaneous preterm births compared to provider-initiated (previously termed 'medically indicated') preterm births. We used a nested case-control design with a sample of 993 women with live births. Cortisol was measured from serum samples collected as part of routine prenatal screening. We tested whether mean-adjusted cortisol fold-change differed by gestational age at delivery or preterm birth subtype using multivariable linear regression. An inverse association between cortisol and gestational age category (trend p = 0.09) was observed. Among deliveries prior to 37 weeks, the mean-adjusted cortisol fold-change values were highest for preterm premature rupture of the membranes (1.10), followed by premature labor (1.03) and provider-initiated preterm birth (1.01), although they did not differ statistically. Cortisol continues to be of interest as a marker of future preterm birth. Augmentation with additional biomarkers should be explored.

Resistant starch: Variation among high amylose rice varieties and its relationship with apparent amylose content, pasting properties and cooking methods.

PubMed

Chen, Ming-Hsuan; Bergman, Christine J; McClung, Anna M; Everette, Jace D; Tabien, Rodante E

2017-11-01

Resistant starch (RS), which is not hydrolyzed in the small intestine, has proposed health benefits. We evaluated 40 high amylose rice varieties for RS content in cooked rice and a 1.9-fold difference was found. Some varieties had more than two-fold greater RS content than a US long-grain intermediate-amylose rice. The high amylose varieties were grouped into four classes according to paste viscosity and gelatinization temperature based on genetic variants of the Waxy and Starch Synthase IIa genes, respectively. RS content was not different between the four paste viscosity-gelatinization temperature classes. Multiple linear regression analysis showed that apparent amylose content and pasting temperature were strong predictors of RS within each class. Two cooking methods, fixed water-to-rice ratio/time and in excess-water/minimum-cook-time, were compared using six rice varieties that were extremes in RS in each of the genetic variant classes, no difference in RS content due to cooking method was observed. Published by Elsevier Ltd.

How Does Your Protein Fold? Elucidating the Apomyoglobin Folding Pathway

PubMed Central

Dyson, H. Jane; Wright, Peter E.

2017-01-01

Conspectus Although each type of protein fold and in some cases individual proteins within a fold classification can have very different mechanisms of folding, the underlying biophysical and biochemical principles that operate to cause a linear polypeptide chain to fold into a globular structure must be the same. In an aqueous solution, the protein takes up the thermodynamically most stable structure, but the pathway along which the polypeptide proceeds in order to reach that structure is a function of the amino acid sequence, which must be the final determining factor, not only in shaping the final folded structure, but in dictating the folding pathway. A number of groups have focused on a single protein or group of proteins, to determine in detail the factors that influence the rate and mechanism of folding in a defined system, with the hope that hypothesis-driven experiments can elucidate the underlying principles governing the folding process. Our research group has focused on the folding of the globin family of proteins, and in particular on the monomeric protein apomyoglobin. Apomyoglobin (apoMb) folds relatively slowly (~2 seconds) via an ensemble of obligatory intermediates that form rapidly after the initiation of folding. The folding pathway can be dissected using rapid-mixing techniques, which can probe processes in the millisecond time range. Stopped-flow measurements detected by circular dichroism (CD) or fluorescence spectroscopy give information on the rates of folding events. Quench-flow experiments utilize the differential rates of hydrogen-deuterium exchange of amide protons protected in parts of the structure that are folded early; protection of amides can be detected by mass spectrometry or proton nuclear magnetic resonance spectroscopy (NMR). In addition, apoMb forms an intermediate at equilibrium at pH ~ 4, which is sufficiently stable for it to be structurally characterized by solution methods such as CD, fluorescence and NMR spectroscopies, and the conformational ensembles formed in the presence of denaturing agents and low pH can be characterized as models for the unfolded states of the protein. Newer NMR techniques such as measurement of residual dipolar couplings in the various partly folded states, and relaxation dispersion measurements to probe invisible states present at low concentrations, have contributed to providing a detailed picture of the apomyoglobin folding pathway. The research summarized in this review was aimed at characterizing and comparing the equilibrium and kinetic intermediates both structurally and dynamically, as well as delineating the complete folding pathway at a residue-specific level, in order to answer the question “What is it about the amino acid sequence that causes each molecule in the unfolded protein ensemble to start folding, and, once started, to proceed towards the formation of the correctly folded three-dimensional structure?” PMID:28032989

Enumeration of Extended m-Regular Linear Stacks.

PubMed

Guo, Qiang-Hui; Sun, Lisa H; Wang, Jian

2016-12-01

The contact map of a protein fold in the two-dimensional (2D) square lattice has arc length at least 3, and each internal vertex has degree at most 2, whereas the two terminal vertices have degree at most 3. Recently, Chen, Guo, Sun, and Wang studied the enumeration of [Formula: see text]-regular linear stacks, where each arc has length at least [Formula: see text] and the degree of each vertex is bounded by 2. Since the two terminal points in a protein fold in the 2D square lattice may form contacts with at most three adjacent lattice points, we are led to the study of extended [Formula: see text]-regular linear stacks, in which the degree of each terminal point is bounded by 3. This model is closed to real protein contact maps. Denote the generating functions of the [Formula: see text]-regular linear stacks and the extended [Formula: see text]-regular linear stacks by [Formula: see text] and [Formula: see text], respectively. We show that [Formula: see text] can be written as a rational function of [Formula: see text]. For a certain [Formula: see text], by eliminating [Formula: see text], we obtain an equation satisfied by [Formula: see text] and derive the asymptotic formula of the numbers of [Formula: see text]-regular linear stacks of length [Formula: see text].

Microsecond time-scale kinetics of transient biochemical reactions

PubMed Central

Mitić, Sandra; Strampraad, Marc J. F.; de Vries, Simon

2017-01-01

To afford mechanistic studies in enzyme kinetics and protein folding in the microsecond time domain we have developed a continuous-flow microsecond time-scale mixing instrument with an unprecedented dead-time of 3.8 ± 0.3 μs. The instrument employs a micro-mixer with a mixing time of 2.7 μs integrated with a 30 mm long flow-cell of 109 μm optical path length constructed from two parallel sheets of silver foil; it produces ultraviolet-visible spectra that are linear in absorbance up to 3.5 with a spectral resolution of 0.4 nm. Each spectrum corresponds to a different reaction time determined by the distance from the mixer outlet, and by the fluid flow rate. The reaction progress is monitored in steps of 0.35 μs for a total duration of ~600 μs. As a proof of principle the instrument was used to study spontaneous protein refolding of pH-denatured cytochrome c. Three folding intermediates were determined: after a novel, extremely rapid initial phase with τ = 4.7 μs, presumably reflecting histidine re-binding to the iron, refolding proceeds with time constants of 83 μs and 345 μs to a coordinatively saturated low-spin iron form in quasi steady state. The time-resolution specifications of our spectrometer for the first time open up the general possibility for comparison of real data and molecular dynamics calculations of biomacromolecules on overlapping time scales. PMID:28973014

The effect of terpene enhancer lipophilicity on the percutaneous permeation of hydrocortisone formulated in HPMC gel systems.

PubMed

El-Kattan, A F; Asbill, C S; Michniak, B B

2000-04-05

The percutaneous permeation of hydrocortisone (HC) was investigated in hairless mouse skin after application of an alcoholic hydrogel using a diffusion cell technique. The formulations contained one of 12 terpenes, the selection of which was based on an increase in their lipophilicity (log P 1.06-5.36). Flux, cumulative receptor concentrations, skin content, and lag time of HC were measured over 24 h and compared with control gels (containing no terpene). Furthermore, HC skin content and the solubility of HC in the alcoholic hydrogel solvent mixture in the presence of terpene were determined, and correlated to the enhancing activity of terpenes. The in vitro permeation experiments with hairless mouse skin revealed that the terpene enhancers varied in their ability to enhance the flux of HC. Nerolidol which possessed the highest lipophilicity (log P = 5.36+/-0.38) provided the greatest enhancement for HC flux (35.3-fold over control). Fenchone (log P = 2.13+/-0.30) exhibited the lowest enhancement of HC flux (10.1-fold over control). In addition, a linear relationship was established between the log P of terpenes and the cumulative amount of HC in the receptor after 24 h (Q(24)). Nerolidol, provided the highest Q(24) (1733+/-93 microg/cm(2)), whereas verbenone produced the lowest Q(24) (653+/-105 microg/cm(2)). Thymol provided the lowest HC skin content (1151+/-293 microg/g), while cineole produced the highest HC skin content (18999+/-5666 microg/g). No correlation was established between the log P of enhancers and HC skin content. A correlation however, existed between the log P of terpenes and the lag time. As log P increased, a linear decrease in lag time was observed. Cymene yielded the shortest HC lag time, while fenchone produced the longest lag time. Also, the increase in the log P of terpenes resulted in a proportional increase in HC solubility in the formulation solvent mixture.

Maternal blood and hair manganese concentrations, fetal growth, and length of gestation in the ISA cohort in Costa Rica

PubMed Central

Mora, Ana M.; van Wendel de Joode, Berna; Mergler, Donna; Córdoba, Leonel; Cano, Camilo; Quesada, Rosario; Smith, Donald R.; Menezes-Filho, José A.; Eskenazi, Brenda

2014-01-01

Background Animal studies have shown that both deficiency and excess manganese (Mn) may result in decreased fetal size and weight, but human studies have reported inconsistent results. Methods We examined the association of blood and hair Mn concentrations measured at different times during pregnancy with fetal growth among term births and length of gestation in a cohort of 380 mother-infant pairs living near banana plantations aerially sprayed with Mn-containing fungicides in Costa Rica. We used linear regression and generalized additive models to test for linear and nonlinear associations. Results Mean (± SD) blood Mn concentration was 24.4 ± 6.6 μg/L and geometric mean (geometric SD) hair Mn concentration was 1.8 (3.2) μg/g. Hair Mn concentrations during the second and third trimesters of gestation were positively related to infant chest circumference (β for 10-fold increase = 0.62 cm; 95% CI: 0.16, 1.08; and β = 0.55 cm; 95% CI: −0.16, 1.26, respectively). Similarly, average maternal hair Mn concentrations during pregnancy were associated with increased chest circumference (β for 10-fold increase = 1.19 cm; 95% CI: 0.43, 1.95) in infants whose mothers did not have gestational anemia, but not in infants of mothers who had gestational anemia (β = 0.39 cm; 95% CI: −0.32, 1.10; pINT = 0.14). All these associations were linear. Blood Mn concentrations did not show consistent linear nor nonlinear relationships with any of the birth outcomes. Conclusions Mn plays an important role in fetal development, but the extent to which environmental exposures may cause adverse health effects to the developing fetus is not well understood. Among women living near banana plantations in Costa Rica, we did not observe linear or nonlinear associations of Mn concentrations with lowered birth weight or head circumference, as reported in previous studies. However, we did find positive linear associations between maternal hair Mn concentrations during pregnancy and infant chest circumference. PMID:25460620

Maternal blood and hair manganese concentrations, fetal growth, and length of gestation in the ISA cohort in Costa Rica.

PubMed

Mora, Ana M; van Wendel de Joode, Berna; Mergler, Donna; Córdoba, Leonel; Cano, Camilo; Quesada, Rosario; Smith, Donald R; Menezes-Filho, José A; Eskenazi, Brenda

2015-01-01

Animal studies have shown that both deficiency and excess manganese (Mn) may result in decreased fetal size and weight, but human studies have reported inconsistent results. We examined the association of blood and hair Mn concentrations measured at different times during pregnancy with fetal growth among term births and length of gestation in a cohort of 380 mother-infant pairs living near banana plantations aerially sprayed with Mn-containing fungicides in Costa Rica. We used linear regression and generalized additive models to test for linear and nonlinear associations Mean (± SD) blood Mn concentration was 24.4 ± 6.6 μg/L and geometric mean (geometric SD) hair Mn concentration was 1.8 (3.2) μg/g. Hair Mn concentrations during the second and third trimesters of gestation were positively related to infant chest circumference (β for 10-fold increase = 0.62 cm; 95% CI: 0.16, 1.08; and β = 0.55 cm; 95% CI: -0.16, 1.26, respectively). Similarly, average maternal hair Mn concentrations during pregnancy were associated with increased chest circumference (β for 10-fold increase = 1.19 cm; 95% CI: 0.43, 1.95) in infants whose mothers did not have gestational anemia, but not in infants of mothers who had gestational anemia (β = 0.39 cm; 95% CI: -0.32, 1.10; pINT=0.14). All these associations were linear. Blood Mn concentrations did not show consistent linear nor nonlinear relationships with any of the birth outcomes Mn plays an important role in fetal development, but the extent to which environmental exposures may cause adverse health effects to the developing fetus is not well understood. Among women living near banana plantations in Costa Rica, we did not observe linear or nonlinear associations of Mn concentrations with lowered birth weight or head circumference, as reported in previous studies. However, we did find positive linear associations between maternal hair Mn concentrations during pregnancy and infant chest circumference. Copyright © 2014 Elsevier Inc. All rights reserved.

Methods for the accurate estimation of confidence intervals on protein folding ϕ-values

PubMed Central

Ruczinski, Ingo; Sosnick, Tobin R.; Plaxco, Kevin W.

2006-01-01

ϕ-Values provide an important benchmark for the comparison of experimental protein folding studies to computer simulations and theories of the folding process. Despite the growing importance of ϕ measurements, however, formulas to quantify the precision with which ϕ is measured have seen little significant discussion. Moreover, a commonly employed method for the determination of standard errors on ϕ estimates assumes that estimates of the changes in free energy of the transition and folded states are independent. Here we demonstrate that this assumption is usually incorrect and that this typically leads to the underestimation of ϕ precision. We derive an analytical expression for the precision of ϕ estimates (assuming linear chevron behavior) that explicitly takes this dependence into account. We also describe an alternative method that implicitly corrects for the effect. By simulating experimental chevron data, we show that both methods accurately estimate ϕ confidence intervals. We also explore the effects of the commonly employed techniques of calculating ϕ from kinetics estimated at non-zero denaturant concentrations and via the assumption of parallel chevron arms. We find that these approaches can produce significantly different estimates for ϕ (again, even for truly linear chevron behavior), indicating that they are not equivalent, interchangeable measures of transition state structure. Lastly, we describe a Web-based implementation of the above algorithms for general use by the protein folding community. PMID:17008714

Emergence of higher order rotational symmetry in the hidden order phase of URu 2Si 2

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

Kanchanavatee, N.; Janoschek, M.; Huang, K.

2016-09-30

Electrical resistivity measurements were performed in this paper as functions of temperature, magnetic field, and angle θ between the magnetic field and the c-axis of a URu 2Si 2 single crystal. The resistivity exhibits a two-fold oscillation as a function of θ at high temperatures, which undergoes a 180°-phase shift (sign change) with decreasing temperature at around 35 K. The hidden order transition is manifested as a minimum in the magnetoresistance and amplitude of the two-fold oscillation. Interestingly, the resistivity also showed four-fold, six-fold, and eight-fold symmetries at the hidden order transition. These higher order symmetries were also detected atmore » low temperatures, which could be a sign of the formation of another pseudogap phase above the superconducting transition, consistent with recent evidence for a pseudogap from point-contact spectroscopy measurements and NMR. Measurements of the magnetisation of single crystalline URu 2Si 2 with the magnetic field applied parallel and perpendicular to the crystallographic c-axis revealed regions with linear temperature dependencies between the hidden order transition temperature and about 25 K. Finally, this T-linear behaviour of the magnetisation may be associated with the formation of a precursor phase or ‘pseudogap’ in the density of states in the vicinity of 30–35 K.« less

Highly efficient implementation of pseudospectral time-dependent density-functional theory for the calculation of excitation energies of large molecules.

PubMed

Cao, Yixiang; Hughes, Thomas; Giesen, Dave; Halls, Mathew D; Goldberg, Alexander; Vadicherla, Tati Reddy; Sastry, Madhavi; Patel, Bhargav; Sherman, Woody; Weisman, Andrew L; Friesner, Richard A

2016-06-15

We have developed and implemented pseudospectral time-dependent density-functional theory (TDDFT) in the quantum mechanics package Jaguar to calculate restricted singlet and restricted triplet, as well as unrestricted excitation energies with either full linear response (FLR) or the Tamm-Dancoff approximation (TDA) with the pseudospectral length scales, pseudospectral atomic corrections, and pseudospectral multigrid strategy included in the implementations to improve the chemical accuracy and to speed the pseudospectral calculations. The calculations based on pseudospectral time-dependent density-functional theory with full linear response (PS-FLR-TDDFT) and within the Tamm-Dancoff approximation (PS-TDA-TDDFT) for G2 set molecules using B3LYP/6-31G*(*) show mean and maximum absolute deviations of 0.0015 eV and 0.0081 eV, 0.0007 eV and 0.0064 eV, 0.0004 eV and 0.0022 eV for restricted singlet excitation energies, restricted triplet excitation energies, and unrestricted excitation energies, respectively; compared with the results calculated from the conventional spectral method. The application of PS-FLR-TDDFT to OLED molecules and organic dyes, as well as the comparisons for results calculated from PS-FLR-TDDFT and best estimations demonstrate that the accuracy of both PS-FLR-TDDFT and PS-TDA-TDDFT. Calculations for a set of medium-sized molecules, including Cn fullerenes and nanotubes, using the B3LYP functional and 6-31G(**) basis set show PS-TDA-TDDFT provides 19- to 34-fold speedups for Cn fullerenes with 450-1470 basis functions, 11- to 32-fold speedups for nanotubes with 660-3180 basis functions, and 9- to 16-fold speedups for organic molecules with 540-1340 basis functions compared to fully analytic calculations without sacrificing chemical accuracy. The calculations on a set of larger molecules, including the antibiotic drug Ramoplanin, the 46-residue crambin protein, fullerenes up to C540 and nanotubes up to 14×(6,6), using the B3LYP functional and 6-31G(**) basis set with up to 8100 basis functions show that PS-FLR-TDDFT CPU time scales as N(2.05) with the number of basis functions. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

An optical flow-based state-space model of the vocal folds.

PubMed

Granados, Alba; Brunskog, Jonas

2017-06-01

High-speed movies of the vocal fold vibration are valuable data to reveal vocal fold features for voice pathology diagnosis. This work presents a suitable Bayesian model and a purely theoretical discussion for further development of a framework for continuum biomechanical features estimation. A linear and Gaussian nonstationary state-space model is proposed and thoroughly discussed. The evolution model is based on a self-sustained three-dimensional finite element model of the vocal folds, and the observation model involves a dense optical flow algorithm. The results show that the method is able to capture different deformation patterns between the computed optical flow and the finite element deformation, controlled by the choice of the model tissue parameters.

The concept of collision strength and its applications

NASA Astrophysics Data System (ADS)

Chang, Yongbin

Collision strength, the measure of strength for a binary collision, hasn't been defined clearly. In practice, many physical arguments have been employed for the purpose and taken for granted. A scattering angle has been widely and intensively used as a measure of collision strength in plasma physics for years. The result of this is complication and unnecessary approximation in deriving some of the basic kinetic equations and in calculating some of the basic physical terms. The Boltzmann equation has a five-fold integral collision term that is complicated. Chandrasekhar and Spitzer's approaches to the linear Fokker-Planck coefficients have several approximations. An effective variable-change technique has been developed in this dissertation as an alternative to scattering angle as the measure of collision strength. By introducing the square of the reduced impulse or its equivalencies as a collision strength variable, many plasma calculations have been simplified. The five-fold linear Boltzmann collision integral and linearized Boltzmann collision integral are simplified to three-fold integrals. The arbitrary order linear Fokker-Planck coefficients are calculated and expressed in a uniform expression. The new theory provides a simple and exact method for describing the equilibrium plasma collision rate, and a precise calculation of the equilibrium relaxation time. It generalizes bimolecular collision reaction rate theory to a reaction rate theory for plasmas. A simple formula of high precision with wide temperature range has been developed for electron impact ionization rates for carbon atoms and ions. The universality of the concept of collision strength is emphasized. This dissertation will show how Arrhenius' chemical reaction rate theory and Thomson's ionization theory can be unified as one single theory under the concept of collision strength, and how many important physical terms in different disciplines, such as activation energy in chemical reaction theory, ionization energy in Thomson's ionization theory, and the Coulomb logarithm in plasma physics, can be unified into a single one---the threshold value of collision strength. The collision strength, which is a measure of a transfer of momentum in units of energy, can be used to reconcile the differences between Descartes' opinion and Leibnitz's opinion about the "true" measure of a force. Like Newton's second law, which provides an instantaneous measure of a force, collision strength, as a cumulative measure of a force, can be regarded as part of a law of force in general.

Lines of Eigenvectors and Solutions to Systems of Linear Differential Equations

ERIC Educational Resources Information Center

Rasmussen, Chris; Keynes, Michael

2003-01-01

The purpose of this paper is to describe an instructional sequence where students invent a method for locating lines of eigenvectors and corresponding solutions to systems of two first order linear ordinary differential equations with constant coefficients. The significance of this paper is two-fold. First, it represents an innovative alternative…

Profile local linear estimation of generalized semiparametric regression model for longitudinal data.

PubMed

Sun, Yanqing; Sun, Liuquan; Zhou, Jie

2013-07-01

This paper studies the generalized semiparametric regression model for longitudinal data where the covariate effects are constant for some and time-varying for others. Different link functions can be used to allow more flexible modelling of longitudinal data. The nonparametric components of the model are estimated using a local linear estimating equation and the parametric components are estimated through a profile estimating function. The method automatically adjusts for heterogeneity of sampling times, allowing the sampling strategy to depend on the past sampling history as well as possibly time-dependent covariates without specifically model such dependence. A [Formula: see text]-fold cross-validation bandwidth selection is proposed as a working tool for locating an appropriate bandwidth. A criteria for selecting the link function is proposed to provide better fit of the data. Large sample properties of the proposed estimators are investigated. Large sample pointwise and simultaneous confidence intervals for the regression coefficients are constructed. Formal hypothesis testing procedures are proposed to check for the covariate effects and whether the effects are time-varying. A simulation study is conducted to examine the finite sample performances of the proposed estimation and hypothesis testing procedures. The methods are illustrated with a data example.

Single-Chain Folding of Synthetic Polymers: A Critical Update.

PubMed

Altintas, Ozcan; Barner-Kowollik, Christopher

2015-11-23

The current contribution serves as a critical update to a previous feature article from us (Macromol. Rapid Commun. 2012, 33, 958-971), and highlights the latest advances in the preparation of single chain polymeric nanoparticles and initial-yet promising-attempts towards mimicking the structure of natural biomacromolecules via single-chain folding of well-defined linear polymers via so-called single chain selective point folding and repeat unit folding. The contribution covers selected examples from the literature published up to ca. September 2015. Our aim is not to provide an exhaustive review but rather highlight a selection of new and exciting examples for single-chain folding based on advanced macromolecular precision chemistry. Initially, the discussion focuses on the synthesis and characterization of single-chain folded structures via selective point folding. The second part of the feature article addresses the folding of well-defined single-chain polymers by means of repeat unit folding. The current state of the art in the field of single-chain folding indicates that repeat unit folding-driven nanoparticle preparation is well-advanced, while initial encouraging steps towards building selective point folding systems have been taken. In addition, a summary of the-in our view-open key questions is provided that may guide future biomimetic design efforts. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Spherical images and inextensible curved folding

NASA Astrophysics Data System (ADS)

Seffen, Keith A.

2018-02-01

In their study, Duncan and Duncan [Proc. R. Soc. London A 383, 191 (1982), 10.1098/rspa.1982.0126] calculate the shape of an inextensible surface folded in two about a general curve. They find the analytical relationships between pairs of generators linked across the fold curve, the shape of the original path, and the fold angle variation along it. They present two special cases of generator layouts for which the fold angle is uniform or the folded curve remains planar, for simplifying practical folding in sheet-metal processes. We verify their special cases by a graphical treatment according to a method of Gauss. We replace the fold curve by a piecewise linear path, which connects vertices of intersecting pairs of hinge lines. Inspired by the d-cone analysis by Farmer and Calladine [Int. J. Mech. Sci. 47, 509 (2005), 10.1016/j.ijmecsci.2005.02.013], we construct the spherical images for developable folding of successive vertices: the operating conditions of the special cases in Duncan and Duncan are then revealed straightforwardly by the geometric relationships between the images. Our approach may be used to synthesize folding patterns for novel deployable and shape-changing surfaces without need of complex calculation.

Improving strand pairing prediction through exploring folding cooperativity

PubMed Central

Jeong, Jieun; Berman, Piotr; Przytycka, Teresa M.

2008-01-01

The topology of β-sheets is defined by the pattern of hydrogen-bonded strand pairing. Therefore, predicting hydrogen bonded strand partners is a fundamental step towards predicting β-sheet topology. At the same time, finding the correct partners is very difficult due to long range interactions involved in strand pairing. Additionally, patterns of aminoacids observed in β-sheet formations are very general and therefore difficult to use for computational recognition of specific contacts between strands. In this work, we report a new strand pairing algorithm. To address above mentioned difficulties, our algorithm attempts to mimic elements of the folding process. Namely, in addition to ensuring that the predicted hydrogen bonded strand pairs satisfy basic global consistency constraints, it takes into account hypothetical folding pathways. Consistently with this view, introducing hydrogen bonds between a pair of strands changes the probabilities of forming hydrogen bonds between other pairs of strand. We demonstrate that this approach provides an improvement over previously proposed algorithms. We also compare the performance of this method to that of a global optimization algorithm that poses the problem as integer linear programming optimization problem and solves it using ILOG CPLEX™ package. PMID:18989036

An adaptive bias - hybrid MD/kMC algorithm for protein folding and aggregation.

PubMed

Peter, Emanuel K; Shea, Joan-Emma

2017-07-05

In this paper, we present a novel hybrid Molecular Dynamics/kinetic Monte Carlo (MD/kMC) algorithm and apply it to protein folding and aggregation in explicit solvent. The new algorithm uses a dynamical definition of biases throughout the MD component of the simulation, normalized in relation to the unbiased forces. The algorithm guarantees sampling of the underlying ensemble in dependency of one average linear coupling factor 〈α〉 τ . We test the validity of the kinetics in simulations of dialanine and compare dihedral transition kinetics with long-time MD-simulations. We find that for low 〈α〉 τ values, kinetics are in good quantitative agreement. In folding simulations of TrpCage and TrpZip4 in explicit solvent, we also find good quantitative agreement with experimental results and prior MD/kMC simulations. Finally, we apply our algorithm to study growth of the Alzheimer Amyloid Aβ 16-22 fibril by monomer addition. We observe two possible binding modes, one at the extremity of the fibril (elongation) and one on the surface of the fibril (lateral growth), on timescales ranging from ns to 8 μs.

X-RAY OUTBURSTS OF ESO 243-49 HLX-1: COMPARISON WITH GALACTIC LOW-MASS X-RAY BINARY TRANSIENTS

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

Yan, Zhen; Zhang, Wenda; Yu, Wenfei

2015-09-20

We studied the outburst properties of the hyper-luminous X-ray source ESO 243-49 HLX-1, using the full set of Swift monitoring observations. We quantified the increase in the waiting time, recurrence time, and e-folding rise timescale along the outburst sequence, and the corresponding decrease in outburst duration, total radiated energy, and e-folding decay timescale, which confirms previous findings. HLX-1 spends less and less time in outburst and more and more time in quiescence, but its peak luminosity remains approximately constant. We compared the HLX-1 outburst properties with those of bright Galactic low-mass X-ray binary transients (LMXBTs). Our spectral analysis strengthens themore » similarity between state transitions in HLX-1 and those in Galactic LMXBTs. We also found that HLX-1 follows the nearly linear correlations between the hard-to-soft state transition luminosity and the peak luminosity, and between the rate of change of X-ray luminosity during the rise phase and the peak luminosity, which indicates that the occurrence of the hard-to-soft state transition of HLX-1 is similar to those of Galactic LMXBTs during outbursts. We found that HLX-1 does not follow the correlations between total radiated energy and peak luminosity, and between total radiated energy and e-folding rise/decay timescales we had previously identified in Galactic LMXBTs. HLX-1 would follow those correlations if the distance were several hundreds of kiloparsecs. However, invoking a much closer distance for HLX-1 is not a viable solution to this problem, as it introduces other, more serious inconsistencies with the observations.« less

Forced and intrinsic variability in the response to increased wind stress of an idealized Southern Ocean

NASA Astrophysics Data System (ADS)

Wilson, Chris; Hughes, Chris W.; Blundell, Jeffrey R.

2015-01-01

use ensemble runs of a three layer, quasi-geostrophic idealized Southern Ocean model to explore the roles of forced and intrinsic variability in response to a linear increase of wind stress imposed over a 30 year period. We find no increase of eastward circumpolar volume transport in response to the increased wind stress. A large part of the resulting time series can be explained by a response in which the eddy kinetic energy is linearly proportional to the wind stress with a possible time lag, but no statistically significant lag is found. However, this simple relationship is not the whole story: several intrinsic time scales also influence the response. We find an e-folding time scale for growth of small perturbations of 1-2 weeks. The energy budget for intrinsic variability at periods shorter than a year is dominated by exchange between kinetic and potential energy. At longer time scales, we find an intrinsic mode with period in the region of 15 years, which is dominated by changes in potential energy and frictional dissipation in a manner consistent with that seen by Hogg and Blundell (2006). A similar mode influences the response to changing wind stress. This influence, robust to perturbations, is different from the supposed linear relationship between wind stress and eddy kinetic energy, and persists for 5-10 years in this model, suggestive of a forced oscillatory mode with period of around 15 years. If present in the real ocean, such a mode would imply a degree of predictability of Southern Ocean dynamics on multiyear time scales.

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

Enhanced Cellular Uptake of Short Polyarginine Peptides through Fatty Acylation and Cyclization

PubMed Central

2015-01-01

Many of the reported arginine-rich cell-penetrating peptides (CPPs) for the enhanced delivery of drugs are linear peptides composed of more than seven arginine residues to retain the cell penetration properties. Herein, we synthesized a class of nine polyarginine peptides containing 5 and 6 arginines, namely, R5 and R6. We further explored the effect of acylation with long chain fatty acids (i.e., octanoic acid, dodecanoic acid, and hexadecanoic acid) and cyclization on the cell penetrating properties of the peptides. The fluorescence-labeled acylated cyclic peptide dodecanoyl-[R5] and linear peptide dodecanoyl-(R5) showed approximately 13.7- and 10.2-fold higher cellular uptake than that of control 5,6-carboxyfluorescein, respectively. The mechanism of the peptide internalization into cells was found to be energy-dependent endocytosis. Dodecanoyl-[R5] and dodecanoyl-[R6] enhanced the intracellular uptake of a fluorescence-labeled cell-impermeable negatively charged phosphopeptide (F′-GpYEEI) in human ovarian cancer cells (SK-OV-3) by 3.4-fold and 5.5-fold, respectively, as shown by flow cytometry. The cellular uptake of F′-GpYEEI in the presence of hexadecanoyl-[R5] was 9.3- and 6.0-fold higher than that in the presence of octanoyl-[R5] and dodecanoyl-[R5], respectively. Dodecanoyl-[R5] enhanced the cellular uptake of the phosphopeptide by 1.4–2.5-fold higher than the corresponding linear peptide dodecanoyl-(R5) and those of representative CPPs, such as hepta-arginine (CR7) and TAT peptide. These results showed that a combination of acylation by long chain fatty acids and cyclization on short arginine-containing peptides can improve their cell-penetrating property, possibly through efficient interaction of rigid positively charged R and hydrophobic dodecanoyl moiety with the corresponding residues in the cell membrane phospholipids. PMID:24978295

Folded Resonant Horns for Power Ultrasonic Applications

NASA Technical Reports Server (NTRS)

Sherrit, Stewart; Askins, Stephen; Gradziel, Michael; Bao, Xiaoqi; Chang, Zensheu; Dolgin, Benjamin; Bar-Cohen, Yoseph; Peterson, Tom

2003-01-01

Folded horns have been conceived as alternatives to straight horns used as resonators and strain amplifiers in power ultrasonic systems. Such systems are used for cleaning, welding, soldering, cutting, and drilling in a variety of industries. In addition, several previous NASA Tech Briefs articles have described instrumented drilling, coring, and burrowing machines that utilize combinations of sonic and ultrasonic vibrational actuation. The main advantage of a folded horn, relative to a straight horn of the same resonance frequency, is that the folded horn can be made shorter (that is, its greatest linear dimension measured from the outside can be made smaller). Alternatively, for a given length, the resonance frequency can be reduced. Hence, the folded-horn concept affords an additional degree of design freedom for reducing the length of an ultrasonic power system that includes a horn.

Viscoelastic measurements after vocal fold scarring in rabbits--short-term results after hyaluronan injection.

PubMed

Hertegård, S; Dahlqvist, A; Goodyer, E

2006-07-01

The scarring model resulted in significant damage and elevated viscoelasticity of the lamina propria. Hyaluronan preparations may alter viscoelasticity in scarred rabbit vocal folds. Vocal fold scarring results in stiffness of the lamina propria and severe voice problems. The aims of this study were to examine the degree of scarring achieved in the experiment and to measure the viscoelastic properties after injection of hyaluronan in rabbit vocal folds. Twenty-two vocal folds from 15 New Zealand rabbits were scarred, 8 vocal folds were controls. After 8 weeks 12 of the scarred vocal folds received injections with 2 types of cross-linked hyaluronan products and 10 scarred folds were injected with saline. After 11 more weeks the animals were sacrificed. After dissection, 15 vocal folds were frozen for viscoelastic measurements, whereas 14 vocal folds were prepared and stained. Measurements were made of the lamina propria thickness. Viscoelasticity was measured on intact vocal folds with a linear skin rheometer (LSR) adapted to laryngeal measurements. Measurements on the digitized slides showed a thickened lamina propria in the scarred samples as compared with the normal vocal folds (p<0.05). The viscoelastic analysis showed a tendency to stiffening of the scarred vocal folds as compared with the normal controls (p=0.05). There was large variation in stiffness between the two injected hyaluronan products.

Restoring paleomagnetic data in complex superposed folding settings: The Boltaña anticline (Southern Pyrenees)

NASA Astrophysics Data System (ADS)

Mochales, T.; Pueyo, E. L.; Casas, A. M.; Barnolas, A.

2016-03-01

Complex kinematic scenarios in fold-and-thrust belts often produce superposed and non-coaxial folding. Interpretation of primary linear indicators must be based on a careful restoration to the undeformed stage following the reverse order of the deformation events. Therefore, sequential restoration to the ancient coordinate system is of key importance to obtain reliable kinematic interpretations using paleomagnetic data. In this paper, a new paleomagnetic study in the western flank of the Boltaña anticline (Southern Pyrenees) illustrates a case study of a complex tectonic setting having superposed, non-coaxial folds. The first stage of NW-SE folding linked to the oblique Boltaña anticline took place during Lutetian times. The second stage was linked to the vertical axis rotation and placed the Boltaña anticline in its present-day N-S configuration. Our data support a long-lasting Lutetian to Priabonian period with main rotational activity during the Bartonian-Priabonian; other authors support a VAR coeval with anticlinal growth. The third stage resulted in southwards tilting related to the emplacement of the N120E striking Guarga basement thrust (Oligocene-Early Miocene). Based on this deformational history, a sequential restoration was applied and compared with the classic bedding correction. At the site scale, single bedding correction gives errors ranging between 31° and - 31° in the estimation of vertical axis rotations. At the locality scale, in sites grouped in three folds (from W to E Arbella, Planillo and San Felizes), the bedding corrected data display rotation values in accordance with those found in the Ainsa Basin by other authors. Sequential restoration (based on the afore-mentioned evolution in three-steps) improves both some locality-means and the internal consistency of the data. Therefore, reasonably-constrained sequential restoration becomes essential to reconstruct the actual history of superposed folding areas.

Sensitivity Gains, Linearity, and Spectral Reproducibility in Nonuniformly Sampled Multidimensional MAS NMR Spectra of High Dynamic Range.

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

Suiter, Christopher L.; Paramasivam, Sivakumar; Hou, Guangjin

Recently, we have demonstrated that considerable inherent sensitivity gains are attained in MAS NMR spectra acquired by nonuniform sampling (NUS) and introduced maximum entropy interpolation (MINT) processing that assures the linearity of transformation between the time and frequency domains. In this report, we examine the utility of the NUS/MINT approach in multidimensional datasets possessing high dynamic range, such as homonuclear 13C–13C correlation spectra. We demonstrate on model compounds and on 1–73-(U-13C,15N)/74–108-(U-15N) E. coli thioredoxin reassembly, that with appropriately constructed 50 % NUS schedules inherent sensitivity gains of 1.7–2.1-fold are readily reached in such datasets. We show that both linearity andmore » line width are retained under these experimental conditions throughout the entire dynamic range of the signals. Furthermore, we demonstrate that the reproducibility of the peak intensities is excellent in the NUS/MINT approach when experiments are repeated multiple times and identical experimental and processing conditions are employed. Finally, we discuss the principles for design and implementation of random exponentially biased NUS sampling schedules for homonuclear 13C–13C MAS correlation experiments that yield high quality artifact-free datasets.« less

Sensitivity gains, linearity, and spectral reproducibility in nonuniformly sampled multidimensional MAS NMR spectra of high dynamic range

PubMed Central

Suiter, Christopher L.; Paramasivam, Sivakumar; Hou, Guangjin; Sun, Shangjin; Rice, David; Hoch, Jeffrey C.; Rovnyak, David

2014-01-01

Recently, we have demonstrated that considerable inherent sensitivity gains are attained in MAS NMR spectra acquired by nonuniform sampling (NUS) and introduced maximum entropy interpolation (MINT) processing that assures the linearity of transformation between the time and frequency domains. In this report, we examine the utility of the NUS/MINT approach in multidimensional datasets possessing high dynamic range, such as homonuclear 13C–13C correlation spectra. We demonstrate on model compounds and on 1–73-(U-13C, 15N)/74–108-(U-15N) E. coli thioredoxin reassembly, that with appropriately constructed 50 % NUS schedules inherent sensitivity gains of 1.7–2.1-fold are readily reached in such datasets. We show that both linearity and line width are retained under these experimental conditions throughout the entire dynamic range of the signals. Furthermore, we demonstrate that the reproducibility of the peak intensities is excellent in the NUS/MINT approach when experiments are repeated multiple times and identical experimental and processing conditions are employed. Finally, we discuss the principles for design and implementation of random exponentially biased NUS sampling schedules for homonuclear 13C–13C MAS correlation experiments that yield high-quality artifact-free datasets. PMID:24752819

Deletion of internal structured repeats increases the stability of a leucine-rich repeat protein, YopM

PubMed Central

Barrick, Doug

2011-01-01

Mapping the stability distributions of proteins in their native folded states provides a critical link between structure, thermodynamics, and function. Linear repeat proteins have proven more amenable to this kind of mapping than globular proteins. C-terminal deletion studies of YopM, a large, linear leucine-rich repeat (LRR) protein, show that stability is distributed quite heterogeneously, yet a high level of cooperativity is maintained [1]. Key components of this distribution are three interfaces that strongly stabilize adjacent sequences, thereby maintaining structural integrity and promoting cooperativity. To better understand the distribution of interaction energy around these critical interfaces, we studied internal (rather than terminal) deletions of three LRRs in this region, including one of these stabilizing interfaces. Contrary to our expectation that deletion of structured repeats should be destabilizing, we find that internal deletion of folded repeats can actually stabilize the native state, suggesting that these repeats are destabilizing, although paradoxically, they are folded in the native state. We identified two residues within this destabilizing segment that deviate from the consensus sequence at a position that normally forms a stacked leucine ladder in the hydrophobic core. Replacement of these nonconsensus residues with leucine is stabilizing. This stability enhancement can be reproduced in the context of nonnative interfaces, but it requires an extended hydrophobic core. Our results demonstrate that different LRRs vary widely in their contribution to stability, and that this variation is context-dependent. These two factors are likely to determine the types of rearrangements that lead to folded, functional proteins, and in turn, are likely to restrict the pathways available for the evolution of linear repeat proteins. PMID:21764506

Towards Batched Linear Solvers on Accelerated Hardware Platforms

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

Haidar, Azzam; Dong, Tingzing Tim; Tomov, Stanimire

2015-01-01

As hardware evolves, an increasingly effective approach to develop energy efficient, high-performance solvers, is to design them to work on many small and independent problems. Indeed, many applications already need this functionality, especially for GPUs, which are known to be currently about four to five times more energy efficient than multicore CPUs for every floating-point operation. In this paper, we describe the development of the main one-sided factorizations: LU, QR, and Cholesky; that are needed for a set of small dense matrices to work in parallel. We refer to such algorithms as batched factorizations. Our approach is based on representingmore » the algorithms as a sequence of batched BLAS routines for GPU-contained execution. Note that this is similar in functionality to the LAPACK and the hybrid MAGMA algorithms for large-matrix factorizations. But it is different from a straightforward approach, whereby each of GPU's symmetric multiprocessors factorizes a single problem at a time. We illustrate how our performance analysis together with the profiling and tracing tools guided the development of batched factorizations to achieve up to 2-fold speedup and 3-fold better energy efficiency compared to our highly optimized batched CPU implementations based on the MKL library on a two-sockets, Intel Sandy Bridge server. Compared to a batched LU factorization featured in the NVIDIA's CUBLAS library for GPUs, we achieves up to 2.5-fold speedup on the K40 GPU.« less

Trends in Utilization of Vocal Fold Injection Procedures.

PubMed

Rosow, David E

2015-11-01

Office-based vocal fold injections have become increasingly popular over the past 15 years. Examination of trends in procedure coding for vocal fold injections in the United States from 2000 to 2012 was undertaken to see if they reflect this shift. The US Part B Medicare claims database was queried from 2000 through 2012 for multiple Current Procedural Terminology codes. Over the period studied, the number of nonoperative laryngoscopic injections (31513, 31570) and operative medialization laryngoplasties (31588) remained constant. Operative vocal fold injection (31571) demonstrated marked linear growth over the 12-year study period, from 744 procedures in 2000 to 4788 in 2012-an increase >640%. The dramatic increased incidence in the use of code 31571 reflects an increasing share of vocal fold injections being performed in the operating room and not in an office setting, running counter to the prevailing trend toward awake, office-based injection procedures. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

Predicting protein folding rate change upon point mutation using residue-level coevolutionary information.

PubMed

Mallik, Saurav; Das, Smita; Kundu, Sudip

2016-01-01

Change in folding kinetics of globular proteins upon point mutation is crucial to a wide spectrum of biological research, such as protein misfolding, toxicity, and aggregations. Here we seek to address whether residue-level coevolutionary information of globular proteins can be informative to folding rate changes upon point mutations. Generating residue-level coevolutionary networks of globular proteins, we analyze three parameters: relative coevolution order (rCEO), network density (ND), and characteristic path length (CPL). A point mutation is considered to be equivalent to a node deletion of this network and respective percentage changes in rCEO, ND, CPL are found linearly correlated (0.84, 0.73, and -0.61, respectively) with experimental folding rate changes. The three parameters predict the folding rate change upon a point mutation with 0.031, 0.045, and 0.059 standard errors, respectively. © 2015 Wiley Periodicals, Inc.

[Superimposed lichen planus pigmentosus].

PubMed

Monteagudo, Benigno; Suarez-Amor, Óscar; Cabanillas, Miguel; de Las Heras, Cristina; Álvarez, Juan Carlos

2014-05-16

Lichen planus pigmentosus is an uncommon variant of lichen planus that is characterized by the insidious onset of dark brown macules in sun-exposed areas and flexural folds. Superimposed linear lichen planus is an exceedingly rare disorder, but it has been found in both lichen planopilaris and lichen planus types. A 39-year-old woman is presented showing a segmental and linear lichen planus associated with non-segmental lesions meeting all criteria for the diagnosis of superimposed linear planus pigmentosus. The segmental lesions were always more pronounced.

Nonlinear Dynamics and Strong Cavity Cooling of Levitated Nanoparticles.

PubMed

Fonseca, P Z G; Aranas, E B; Millen, J; Monteiro, T S; Barker, P F

2016-10-21

Optomechanical systems explore and exploit the coupling between light and the mechanical motion of macroscopic matter. A nonlinear coupling offers rich new physics, in both quantum and classical regimes. We investigate a dynamic, as opposed to the usually studied static, nonlinear optomechanical system, comprising a nanosphere levitated in a hybrid electro-optical trap. The cavity offers readout of both linear-in-position and quadratic-in-position (nonlinear) light-matter coupling, while simultaneously cooling the nanosphere, for indefinite periods of time and in high vacuum. We observe the cooling dynamics via both linear and nonlinear coupling. As the background gas pressure was lowered, we observed a greater than 1000-fold reduction in temperature before temperatures fell below readout sensitivity in the present setup. This Letter opens the way to strongly coupled quantum dynamics between a cavity and a nanoparticle largely decoupled from its environment.

Application of catalytic adsorptive stripping voltammetry of the cobalt-alpha-benzil dioxime complex to analysis of cobalt traces in metallic zinc.

PubMed

Bobrowski, A

1994-05-01

The catalytic adsorptive stripping voltammetric method with alpha-benzil dioxime and nitrite affords numerous advantages in cobalt determination. The detailed conditions of the determination of the cobalt traces in metallic zinc by catalytic adsorptive stripping voltammetry have been investigated. Both the linear sweep and the differential pulse stripping modes can be used with similar sensitivity. Possible interferences by Mn, Pb, Cu, Ni and Fe are evaluated. In the presence of 5 x 10(5) fold excess of Zn the linear dependence of the cobalt CASV peak current on concentration ranged from 0.05 mug/l to 3 mug/l. Optimal conditions include the accumulation potential of -0.65 V and the accumulation time of 10 sec. The results of the determination of 10(-5)% level of Co in the metallic zinc showed good reproducibility (relative standard deviation, RSD = 0.07) and reliability.

Nonlinear Dynamics and Strong Cavity Cooling of Levitated Nanoparticles

NASA Astrophysics Data System (ADS)

Fonseca, P. Z. G.; Aranas, E. B.; Millen, J.; Monteiro, T. S.; Barker, P. F.

2016-10-01

Optomechanical systems explore and exploit the coupling between light and the mechanical motion of macroscopic matter. A nonlinear coupling offers rich new physics, in both quantum and classical regimes. We investigate a dynamic, as opposed to the usually studied static, nonlinear optomechanical system, comprising a nanosphere levitated in a hybrid electro-optical trap. The cavity offers readout of both linear-in-position and quadratic-in-position (nonlinear) light-matter coupling, while simultaneously cooling the nanosphere, for indefinite periods of time and in high vacuum. We observe the cooling dynamics via both linear and nonlinear coupling. As the background gas pressure was lowered, we observed a greater than 1000-fold reduction in temperature before temperatures fell below readout sensitivity in the present setup. This Letter opens the way to strongly coupled quantum dynamics between a cavity and a nanoparticle largely decoupled from its environment.

Achieving high peak capacity production for gas chromatography and comprehensive two-dimensional gas chromatography by minimizing off-column peak broadening.

PubMed

Wilson, Ryan B; Siegler, W Christopher; Hoggard, Jamin C; Fitz, Brian D; Nadeau, Jeremy S; Synovec, Robert E

2011-05-27

By taking into consideration band broadening theory and using those results to select experimental conditions, and also by reducing the injection pulse width, peak capacity production (i.e., peak capacity per separation time) is substantially improved for one dimensional (1D-GC) and comprehensive two dimensional (GC×GC) gas chromatography. A theoretical framework for determining the optimal linear gas velocity (the linear gas velocity producing the minimum H), from experimental parameters provides an in-depth understanding of the potential for GC separations in the absence of extra-column band broadening. The extra-column band broadening is referred to herein as off-column band broadening since it is additional band broadening not due to the on-column separation processes. The theory provides the basis to experimentally evaluate and improve temperature programmed 1D-GC separations, but in order to do so with a commercial 1D-GC instrument platform, off-column band broadening from injection and detection needed to be significantly reduced. Specifically for injection, a resistively heated transfer line is coupled to a high-speed diaphragm valve to provide a suitable injection pulse width (referred to herein as modified injection). Additionally, flame ionization detection (FID) was modified to provide a data collection rate of 5kHz. The use of long, relatively narrow open tubular capillary columns and a 40°C/min programming rate were explored for 1D-GC, specifically a 40m, 180μm i.d. capillary column operated at or above the optimal average linear gas velocity. Injection using standard auto-injection with a 1:400 split resulted in an average peak width of ∼1.5s, hence a peak capacity production of 40peaks/min. In contrast, use of modified injection produced ∼500ms peak widths for 1D-GC, i.e., a peak capacity production of 120peaks/min (a 3-fold improvement over standard auto-injection). Implementation of modified injection resulted in retention time, peak width, peak height, and peak area average RSD%'s of 0.006, 0.8, 3.4, and 4.0%, respectively. Modified injection onto the first column of a GC×GC coupled with another high-speed valve injection onto the second column produced an instrument with high peak capacity production (500-800peaks/min), ∼5-fold to 8-fold higher than typically reported for GC×GC. Copyright © 2011 Elsevier B.V. All rights reserved.

Greenstone belts: Their components and structure

NASA Technical Reports Server (NTRS)

Vearncombe, J. R.; Barton, J. M., Jr.; Vanreenen, D. D.; Phillips, G. N.; Wilson, A. H.

1986-01-01

Greenstone sucessions are defined as the nongranitoid component of granitoid-greenstone terrain and are linear to irregular in shape and where linear are termed belts. The chemical composition of greenstones is described. Also discussed are the continental environments of greenstone successions. The effects of contact with granitoids, geophysical properties, recumbent folds and late formation structures upon greenstones are examined. Large stratigraphy thicknesses are explained.

Adaptive deformable model for colonic polyp segmentation and measurement on CT colonography

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

Yao Jianhua; Summers, Ronald M.

2007-05-15

Polyp size is one important biomarker for the malignancy risk of a polyp. This paper presents an improved approach for colonic polyp segmentation and measurement on CT colonography images. The method is based on a combination of knowledge-guided intensity adjustment, fuzzy clustering, and adaptive deformable model. Since polyps on haustral folds are the most difficult to be segmented, we propose a dual-distance algorithm to first identify voxels on the folds, and then introduce a counter-force to control the model evolution. We derive linear and volumetric measurements from the segmentation. The experiment was conducted on 395 patients with 83 polyps, ofmore » which 43 polyps were on haustral folds. The results were validated against manual measurement from the optical colonoscopy and the CT colonography. The paired t-test showed no significant difference, and the R{sup 2} correlation was 0.61 for the linear measurement and 0.98 for the volumetric measurement. The mean Dice coefficient for volume overlap between automatic and manual segmentation was 0.752 (standard deviation 0.154)« less

On Ramachandran angles, closed strings and knots in protein structure

NASA Astrophysics Data System (ADS)

Chen, Si; Niemi, Antti J.

2016-08-01

The Ramachandran angles (φ,\\psi ) of a protein backbone form the vertices of a piecewise geodesic curve on the surface of a torus. When the ends of the curve are connected to each other similarly, by a geodesic, the result is a closed string that in general wraps around the torus a number of times both in the meridional and the longitudinal directions. The two wrapping numbers are global characteristics of the protein structure. A statistical analysis of the wrapping numbers in terms of crystallographic x-ray structures in the protein data bank (PDB) reveals that proteins have no net chirality in the ϕ direction but in the ψ direction, proteins prefer to display chirality. A comparison between the wrapping numbers and the concept of folding index discloses a non-linearity in their relationship. Thus these three integer valued invariants can be used in tandem, to scrutinize and classify the global loop structure of individual PDB proteins, in terms of the overall fold topology.

Kinematics of fault-related folding derived from a sandbox experiment

NASA Astrophysics Data System (ADS)

Bernard, Sylvain; Avouac, Jean-Philippe; Dominguez, StéPhane; Simoes, Martine

2007-03-01

We analyze the kinematics of fault tip folding at the front of a fold-and-thrust wedge using a sandbox experiment. The analog model consists of sand layers intercalated with low-friction glass bead layers, deposited in a glass-sided experimental device and with a total thickness h = 4.8 cm. A computerized mobile backstop induces progressive horizontal shortening of the sand layers and therefore thrust fault propagation. Active deformation at the tip of the forward propagating basal décollement is monitored along the cross section with a high-resolution CCD camera, and the displacement field between pairs of images is measured from the optical flow technique. In the early stage, when cumulative shortening is less than about h/10, slip along the décollement tapers gradually to zero and the displacement gradient is absorbed by distributed deformation of the overlying medium. In this stage of detachment tip folding, horizontal displacements decrease linearly with distance toward the foreland. Vertical displacements reflect a nearly symmetrical mode of folding, with displacements varying linearly between relatively well defined axial surfaces. When the cumulative slip on the décollement exceeds about h/10, deformation tends to localize on a few discrete shear bands at the front of the system, until shortening exceeds h/8 and deformation gets fully localized on a single emergent frontal ramp. The fault geometry subsequently evolves to a sigmoid shape and the hanging wall deforms by simple shear as it overthrusts the flat ramp system. As long as strain localization is not fully established, the sand layers experience a combination of thickening and horizontal shortening, which induces gradual limb rotation. The observed kinematics can be reduced to simple analytical expressions that can be used to restore fault tip folds, relate finite deformation to incremental folding, and derive shortening rates from deformed geomorphic markers or growth strata.

Analytic solutions to modelling exponential and harmonic functions using Chebyshev polynomials: fitting frequency-domain lifetime images with photobleaching.

PubMed

Malachowski, George C; Clegg, Robert M; Redford, Glen I

2007-12-01

A novel approach is introduced for modelling linear dynamic systems composed of exponentials and harmonics. The method improves the speed of current numerical techniques up to 1000-fold for problems that have solutions of multiple exponentials plus harmonics and decaying components. Such signals are common in fluorescence microscopy experiments. Selective constraints of the parameters being fitted are allowed. This method, using discrete Chebyshev transforms, will correctly fit large volumes of data using a noniterative, single-pass routine that is fast enough to analyse images in real time. The method is applied to fluorescence lifetime imaging data in the frequency domain with varying degrees of photobleaching over the time of total data acquisition. The accuracy of the Chebyshev method is compared to a simple rapid discrete Fourier transform (equivalent to least-squares fitting) that does not take the photobleaching into account. The method can be extended to other linear systems composed of different functions. Simulations are performed and applications are described showing the utility of the method, in particular in the area of fluorescence microscopy.

Effects of matrix composition, microstructure, and viscoelasticity on the behaviors of vocal fold fibroblasts cultured in three-dimensional hydrogel networks.

PubMed

Farran, Alexandra J E; Teller, Sean S; Jha, Amit K; Jiao, Tong; Hule, Rohan A; Clifton, Rodney J; Pochan, Darrin P; Duncan, Randall L; Jia, Xinqiao

2010-04-01

Vocal fold diseases and disorders are difficult to treat surgically or therapeutically. Tissue engineering offers an alternative strategy for the restoration of functional vocal folds. As a first step toward vocal fold tissue engineering, we investigated the responses of primary vocal fold fibroblasts (PVFFs) to two types of collagen and hyaluronic acid (HA)-based hydrogels that are compositionally similar, but structurally variable and mechanically different. Type A hydrogels were composed of mature collagen fibers reinforced by oxidized HA, whereas type B hydrogels contained immature collagen fibrils interpenetrated in an amorphous, covalently cross-linked HA matrix. PVFFs encapsulated in either matrix adopted a fibroblastic morphology and expressed genes related to important extracellular matrix proteins. DNA analysis indicated a linear growth profile for cells encapsulated in type B gels from day 0 to 21, in contrast to an initial dormant, nonproliferative period from day 0 to 3 experienced by cells in type A gels. At the end of the culture, similar DNA content was detected in both types of constructs. A reduction in collagen content was observed for both types of constructs after 28 days of culture, with type A constructs generally retaining higher amounts of collagen than type B constructs. The HA content in the constructs decreased steadily throughout the culture, with type A constructs consistently exhibiting less HA than type B constructs. Using the torsional wave analysis, we found that the elastic moduli for type A constructs decreased sharply during the first week of culture, followed by 2 weeks of matrix stabilization without significant changes in matrix stiffness. Conversely, the elastic modulus for type B constructs increased moderately over time. It is postulated that PVFFs residing in gels alter the matrix organization, chemical compositions, and viscoelasticity through cell-mediated remodeling processes.

Micromechanical-biochemical studies of mitotic chromosome elasticity and structure

NASA Astrophysics Data System (ADS)

Poirier, Michael Guy

The structure of mitotic chromosomes was studied by combining micromechanical force measurements with microfluidic biochemical exposures. Our method is to use glass micropipettes attached to either end of a single chromosome to do mechanical experiments in the extracellular buffer. A third pipette can be used to locally 'spray' reactants so as to carry out dynamical mechanical-chemical experiments. The following elastic properties of mitotic chromosomes are found: Young's modulus, Y = 300 Pa; Poisson ratio, sigma = 0.1; Bending rigidity, B = 1 x 10 -22 J·m; Internal viscosity, eta' = 100 kg/m·sec; Volume fraction, ϕ = 0.7; Extensions of less than 3 times the relaxed length are linear and reversible; Extensions beyond 30 fold exhibit a force plateau at 15 nN and convert the chromosome to a disperse ghost-like state with little change in chromatin structure; Mitotic chromosomes are relatively isotropic; dsDNA cuts of at least every 3 kb cause the a mitotic chromosomes to fall apart; dsDNA cuts less frequently than every 50 kb do not affect mitotic chromosome structure. These results lead to the conclusion that mitotic chromosomes are a network crosslinked every 50 kb between which chromatin is fold by chromatin folding proteins, which are likely to be condensins.

New insights into the folding of a β-sheet miniprotein in a reduced space of collective hydrogen bond variables: application to a hydrodynamic analysis of the folding flow.

PubMed

Kalgin, Igor V; Caflisch, Amedeo; Chekmarev, Sergei F; Karplus, Martin

2013-05-23

A new analysis of the 20 μs equilibrium folding/unfolding molecular dynamics simulations of the three-stranded antiparallel β-sheet miniprotein (beta3s) in implicit solvent is presented. The conformation space is reduced in dimensionality by introduction of linear combinations of hydrogen bond distances as the collective variables making use of a specially adapted principal component analysis (PCA); i.e., to make structured conformations more pronounced, only the formed bonds are included in determining the principal components. It is shown that a three-dimensional (3D) subspace gives a meaningful representation of the folding behavior. The first component, to which eight native hydrogen bonds make the major contribution (four in each beta hairpin), is found to play the role of the reaction coordinate for the overall folding process, while the second and third components distinguish the structured conformations. The representative points of the trajectory in the 3D space are grouped into conformational clusters that correspond to locally stable conformations of beta3s identified in earlier work. A simplified kinetic network based on the three components is constructed, and it is complemented by a hydrodynamic analysis. The latter, making use of "passive tracers" in 3D space, indicates that the folding flow is much more complex than suggested by the kinetic network. A 2D representation of streamlines shows there are vortices which correspond to repeated local rearrangement, not only around minima of the free energy surface but also in flat regions between minima. The vortices revealed by the hydrodynamic analysis are apparently not evident in folding pathways generated by transition-path sampling. Making use of the fact that the values of the collective hydrogen bond variables are linearly related to the Cartesian coordinate space, the RMSD between clusters is determined. Interestingly, the transition rates show an approximate exponential correlation with distance in the hydrogen bond subspace. Comparison with the many published studies shows good agreement with the present analysis for the parts that can be compared, supporting the robust character of our understanding of this "hydrogen atom" of protein folding.

Topology of polymer chains under nanoscale confinement.

PubMed

Satarifard, Vahid; Heidari, Maziar; Mashaghi, Samaneh; Tans, Sander J; Ejtehadi, Mohammad Reza; Mashaghi, Alireza

2017-08-24

Spatial confinement limits the conformational space accessible to biomolecules but the implications for bimolecular topology are not yet known. Folded linear biopolymers can be seen as molecular circuits formed by intramolecular contacts. The pairwise arrangement of intra-chain contacts can be categorized as parallel, series or cross, and has been identified as a topological property. Using molecular dynamics simulations, we determine the contact order distributions and topological circuits of short semi-flexible linear and ring polymer chains with a persistence length of l p under a spherical confinement of radius R c . At low values of l p /R c , the entropy of the linear chain leads to the formation of independent contacts along the chain and accordingly, increases the fraction of series topology with respect to other topologies. However, at high l p /R c , the fraction of cross and parallel topologies are enhanced in the chain topological circuits with cross becoming predominant. At an intermediate confining regime, we identify a critical value of l p /R c , at which all topological states have equal probability. Confinement thus equalizes the probability of more complex cross and parallel topologies to the level of the more simple, non-cooperative series topology. Moreover, our topology analysis reveals distinct behaviours for ring- and linear polymers under weak confinement; however, we find no difference between ring- and linear polymers under strong confinement. Under weak confinement, ring polymers adopt parallel and series topologies with equal likelihood, while linear polymers show a higher tendency for series arrangement. The radial distribution analysis of the topology reveals a non-uniform effect of confinement on the topology of polymer chains, thereby imposing more pronounced effects on the core region than on the confinement surface. Additionally, our results reveal that over a wide range of confining radii, loops arranged in parallel and cross topologies have nearly the same contact orders. Such degeneracy implies that the kinetics and transition rates between the topological states cannot be solely explained by contact order. We expect these findings to be of general importance in understanding chaperone assisted protein folding, chromosome architecture, and the evolution of molecular folds.

Three decades (1983-2010) of contaminant trends in East Greenland polar bears (Ursus maritimus). Part 2: brominated flame retardants.

PubMed

Dietz, Rune; Rigét, Frank F; Sonne, Christian; Born, Erik W; Bechshøft, Thea; McKinney, Melissa A; Drimmie, Robert J; Muir, Derek C G; Letcher, Robert J

2013-09-01

Brominated flame retardants were determined in adipose tissues from 294 polar bears (Ursus maritimus) sampled in East Greenland in 23 of the 28years between 1983 and 2010. Significant linear increases were found for sum polybrominated diphenyl ether (ΣPBDE), BDE100, BDE153, and hexabromocyclododecane (HBCD). Average increases of 5.0% per year (range: 2.9-7.6%/year) were found for the subadult polar bears. BDE47 and BDE99 concentrations did not show a significant linear trend over time, but rather a significant non-linear trend peaking between 2000 and 2004. The average ΣPBDE concentrations increased 2.3 fold from 25.0ng/g lw (95% C.I.: 15.3-34.7ng/g lw) in 1983-1986 to 58.5ng/g lw (95% C.I.: 43.6-73.4ng/g lw) in 2006-2010. Similar but fewer statistically significant trends were found for adult females and adult males likely due to smaller sample size and years. Analyses of δ(15)N and δ(13)C stable isotopes in hair revealed no clear linear temporal trends in trophic level or carbon source, respectively, and non-linear trends differed among sex and age groups. These increasing concentrations of organobromine contaminants contribute to complex organohalogen mixture, already causing health effects to the East Greenland polar bears. Copyright © 2012 Elsevier Ltd. All rights reserved.

Alternate approaches to future electron-positron linear colliders

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

Loew, G.A.

1998-07-01

The purpose of this article is two-fold: to review the current international status of various design approaches to the next generation of e{sup +}e{sup {minus}} linear colliders, and on the occasion of his 80th birthday, to celebrate Richard B. Neal`s many contributions to the field of linear accelerators. As it turns out, combining these two tasks is a rather natural enterprise because of Neal`s long professional involvement and insight into many of the problems and options which the international e{sup +}e{sup {minus}} linear collider community is currently studying to achieve a practical design for a future machine.

Detection and mapping of delays in early cortical folding derived from in utero MRI

NASA Astrophysics Data System (ADS)

Habas, Piotr A.; Rajagopalan, Vidya; Scott, Julia A.; Kim, Kio; Roosta, Ahmad; Rousseau, Francois; Barkovich, A. James; Glenn, Orit A.; Studholme, Colin

2011-03-01

Understanding human brain development in utero and detecting cortical abnormalities related to specific clinical conditions is an important area of research. In this paper, we describe and evaluate methodology for detection and mapping of delays in early cortical folding from population-based studies of fetal brain anatomies imaged in utero. We use a general linear modeling framework to describe spatiotemporal changes in curvature of the developing brain and explore the ability to detect and localize delays in cortical folding in the presence of uncertainty in estimation of the fetal age. We apply permutation testing to examine which regions of the brain surface provide the most statistical power to detect a given folding delay at a given developmental stage. The presented methodology is evaluated using MR scans of fetuses with normal brain development and gestational ages ranging from 20.57 to 27.86 weeks. This period is critical in early cortical folding and the formation of the primary and secondary sulci. Finally, we demonstrate a clinical application of the framework for detection and localization of folding delays in fetuses with isolated mild ventriculomegaly.

On the polymer physics origins of protein folding thermodynamics.

PubMed

Taylor, Mark P; Paul, Wolfgang; Binder, Kurt

2016-11-07

A remarkable feature of the spontaneous folding of many small proteins is the striking similarity in the thermodynamics of the folding process. This process is characterized by simple two-state thermodynamics with large and compensating changes in entropy and enthalpy and a funnel-like free energy landscape with a free-energy barrier that varies linearly with temperature. One might attribute the commonality of this two-state folding behavior to features particular to these proteins (e.g., chain length, hydrophobic/hydrophilic balance, attributes of the native state) or one might suspect that this similarity in behavior has a more general polymer-physics origin. Here we show that this behavior is also typical for flexible homopolymer chains with sufficiently short range interactions. Two-state behavior arises from the presence of a low entropy ground (folded) state separated from a set of high entropy disordered (unfolded) states by a free energy barrier. This homopolymer model exhibits a funneled free energy landscape that reveals a complex underlying dynamics involving competition between folding and non-folding pathways. Despite the presence of multiple pathways, this simple physics model gives the robust result of two-state thermodynamics for both the cases of folding from a basin of expanded coil states and from a basin of compact globule states.

On the polymer physics origins of protein folding thermodynamics

NASA Astrophysics Data System (ADS)

Taylor, Mark P.; Paul, Wolfgang; Binder, Kurt

2016-11-01

A remarkable feature of the spontaneous folding of many small proteins is the striking similarity in the thermodynamics of the folding process. This process is characterized by simple two-state thermodynamics with large and compensating changes in entropy and enthalpy and a funnel-like free energy landscape with a free-energy barrier that varies linearly with temperature. One might attribute the commonality of this two-state folding behavior to features particular to these proteins (e.g., chain length, hydrophobic/hydrophilic balance, attributes of the native state) or one might suspect that this similarity in behavior has a more general polymer-physics origin. Here we show that this behavior is also typical for flexible homopolymer chains with sufficiently short range interactions. Two-state behavior arises from the presence of a low entropy ground (folded) state separated from a set of high entropy disordered (unfolded) states by a free energy barrier. This homopolymer model exhibits a funneled free energy landscape that reveals a complex underlying dynamics involving competition between folding and non-folding pathways. Despite the presence of multiple pathways, this simple physics model gives the robust result of two-state thermodynamics for both the cases of folding from a basin of expanded coil states and from a basin of compact globule states.

Use of a capillary electrophoresis instrument with laser-induced fluorescence detection for DNA quantitation. Comparison of YO-PRO-1 and PicoGreen assays.

PubMed

Guillo, Christelle; Ferrance, Jerome P; Landers, James P

2006-04-28

Highly selective and sensitive assays are required for detection and quantitation of the small masses of DNA typically encountered in clinical and forensic settings. High detection sensitivity is achieved using fluorescent labeling dyes and detection techniques such as spectrofluorometers, microplate readers and cytometers. This work describes the use of a laser-induced fluorescence (LIF) detector in conjunction with a commercial capillary electrophoresis instrument for DNA quantitation. PicoGreen and YO-PRO-1, two fluorescent DNA labeling dyes, were used to assess the potential of the system for routine DNA analysis. Linearity, reproducibility, sensitivity, limits of detection and quantitation, and sample stability were examined for the two assays. The LIF detector response was found to be linear (R2 > 0.999) and reproducible (RSD < 9%) in both cases. The PicoGreen assay displayed lower limits of detection and quantitation (20 pg and 60 pg, respectively) than the YO-PRO-1 assay (60 pg and 260 pg, respectively). Although a small variation in fluorescence was observed for the DNA/dye complexes over time, quantitation was not significantly affected and the solutions were found to be relatively stable for 80 min. The advantages of the technique include a 4- to 40-fold reduction in the volume of sample required compared to traditional assays, a 2- to 20-fold reduction in the volume of reagents consumed, fast and automated analysis, and low cost (no specific instrumentation required).

The importance of hyaluronic acid in vocal fold biomechanics.

PubMed

Chan, R W; Gray, S D; Titze, I R

2001-06-01

This study examined the influence of hyaluronic acid (HA) on the biomechanical properties of the human vocal fold cover (the superficial layer of the lamina propria). Vocal fold tissues were freshly excised from 5 adult male cadavers and were treated with bovine testicular hyaluronidase to selectively remove HA from the lamina propria extracellular matrix (ECM). Linear viscoelastic shear properties (elastic shear modulus and dynamic viscosity) of the tissue samples before and after enzymatic treatment were quantified as a function of frequency (0.01 to 15 Hz) by a parallel-plate rotational rheometer at 37 degrees C. On removing HA from the vocal fold ECM, the elastic shear modulus (G' ) or stiffness of the vocal fold cover decreased by an average of around 35%, while the dynamic viscosity (eta') increased by 70% at higher frequencies (>1 Hz). The results suggested that HA plays an important role in determining the biomechanical properties of the vocal fold cover. As a highly hydrated glycosaminoglycan in the vocal fold ECM, it likely contributes to the maintenance of an optimal tissue viscosity that may facilitate phonation, and an optimal tissue stiffness that may be important for vocal fundamental frequency control. HA has been proposed as a potential bioimplant for the surgical repair of vocal fold ECM defects (eg, vocal fold scarring and sulcus vocalis). Our results suggested that such clinical use may be potentially optimal for voice production from a biomechanical perspective.

Mercury in the Soil of Two Contrasting Watersheds in the Eastern United States

PubMed Central

Burns, Douglas A.; Woodruff, Laurel G.; Bradley, Paul M.; Cannon, William F.

2014-01-01

Soil represents the largest store of mercury (Hg) in terrestrial ecosystems, and further study of the factors associated with soil Hg storage is needed to address concerns about the magnitude and persistence of global environmental Hg bioaccumulation. To address this need, we compared total Hg and methyl Hg concentrations and stores in the soil of different landscapes in two watersheds in different geographic settings with similar and relatively high methyl Hg concentrations in surface waters and biota, Fishing Brook, Adirondack Mountains, New York, and McTier Creek, Coastal Plain, South Carolina. Median total Hg concentrations and stores in organic and mineral soil samples were three-fold greater at Fishing Brook than at McTier Creek. Similarly, median methyl Hg concentrations were about two-fold greater in Fishing Brook soil than in McTier Creek soil, but this difference was significant only for mineral soil samples, and methyl Hg stores were not significantly different among these watersheds. In contrast, the methyl Hg/total Hg ratio was significantly greater at McTier Creek suggesting greater climate-driven methylation efficiency in the Coastal Plain soil than that of the Adirondack Mountains. The Adirondack soil had eight-fold greater soil organic matter than that of the Coastal Plain, consistent with greater total Hg stores in the northern soil, but soil organic matter – total Hg relations differed among the sites. A strong linear relation was evident at McTier Creek (r2 = 0.68; p<0.001), but a linear relation at Fishing Brook was weak (r2 = 0.13; p<0.001) and highly variable across the soil organic matter content range, suggesting excess Hg binding capacity in the Adirondack soil. These results suggest greater total Hg turnover time in Adirondack soil than that of the Coastal Plain, and that future declines in stream water Hg concentrations driven by declines in atmospheric Hg deposition will be more gradual and prolonged in the Adirondacks. PMID:24551042

Revision for prosthetic joint infection following hip arthroplasty: Evidence from the National Joint Registry.

PubMed

Lenguerrand, E; Whitehouse, M R; Beswick, A D; Jones, S A; Porter, M L; Blom, A W

2017-06-01

We used the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man (NJR) to investigate the risk of revision due to prosthetic joint infection (PJI) for patients undergoing primary and revision hip arthroplasty, the changes in risk over time, and the overall burden created by PJI. We analysed revision total hip arthroplasties (THAs) performed due to a diagnosis of PJI and the linked index procedures recorded in the NJR between 2003 and 2014. The cohort analysed consisted of 623 253 index primary hip arthroplasties, 63 222 index revision hip arthroplasties and 7585 revision THAs performed due to a diagnosis of PJI. The prevalence, cumulative incidence functions and the burden of PJI (total procedures) were calculated. Overall linear trends were investigated with log-linear regression. We demonstrated a prevalence of revision THA due to prosthetic joint infection of 0.4/100 procedures following primary and 1.6/100 procedures following revision hip arthroplasty. The prevalence of revision due to PJI in the three months following primary hip arthroplasty has risen 2.3-fold (95% confidence interval (CI) 1.3 to 4.1) between 2005 and 2013, and 3.0-fold (95% CI 1.1 to 8.5) following revision hip arthroplasty. Over 1000 procedures are performed annually as a consequence of hip PJI, an increase of 2.6-fold between 2005 and 2013. Although the risk of revision due to PJI following hip arthroplasty is low, it is rising and, coupled with the established and further predicted increased incidence of both primary and revision hip arthroplasty, this represents a growing and substantial treatment burden. Cite this article : E. Lenguerrand, M. R. Whitehouse, A. D. Beswick, S. A. Jones, M. L. Porter, A. W. Blom. Revision for prosthetic joint infection following hip arthroplasty: Evidence from the National Joint Registry. Bone Joint Res 2017;6:391-398. DOI: 10.1302/2046-3758.66.BJR-2017-0003.R1. © 2017 Lenguerrand et al.

A continuous-flow capillary mixing method to monitor reactions on the microsecond time scale.

PubMed Central

Shastry, M C; Luck, S D; Roder, H

1998-01-01

A continuous-flow capillary mixing apparatus, based on the original design of Regenfuss et al. (Regenfuss, P., R. M. Clegg, M. J. Fulwyler, F. J. Barrantes, and T. M. Jovin. 1985. Rev. Sci. Instrum. 56:283-290), has been developed with significant advances in mixer design, detection method and data analysis. To overcome the problems associated with the free-flowing jet used for observation in the original design (instability, optical artifacts due to scattering, poor definition of the geometry), the solution emerging from the capillary is injected directly into a flow-cell joined to the tip of the outer capillary via a ground-glass joint. The reaction kinetics are followed by measuring fluorescence versus distance downstream from the mixer, using an Hg(Xe) arc lamp for excitation and a digital camera with a UV-sensitized CCD detector for detection. Test reactions involving fluorescent dyes indicate that mixing is completed within 15 micros of its initiation and that the dead time of the measurement is 45 +/- 5 micros, which represents a >30-fold improvement in time resolution over conventional stopped-flow instruments. The high sensitivity and linearity of the CCD camera have been instrumental in obtaining artifact-free kinetic data over the time window from approximately 45 micros to a few milliseconds with signal-to-noise levels comparable to those of conventional methods. The scope of the method is discussed and illustrated with an example of a protein folding reaction. PMID:9591695

Folded concave penalized learning in identifying multimodal MRI marker for Parkinson’s disease

PubMed Central

Liu, Hongcheng; Du, Guangwei; Zhang, Lijun; Lewis, Mechelle M.; Wang, Xue; Yao, Tao; Li, Runze; Huang, Xuemei

2016-01-01

Background Brain MRI holds promise to gauge different aspects of Parkinson’s disease (PD)-related pathological changes. Its analysis, however, is hindered by the high-dimensional nature of the data. New method This study introduces folded concave penalized (FCP) sparse logistic regression to identify biomarkers for PD from a large number of potential factors. The proposed statistical procedures target the challenges of high-dimensionality with limited data samples acquired. The maximization problem associated with the sparse logistic regression model is solved by local linear approximation. The proposed procedures then are applied to the empirical analysis of multimodal MRI data. Results From 45 features, the proposed approach identified 15 MRI markers and the UPSIT, which are known to be clinically relevant to PD. By combining the MRI and clinical markers, we can enhance substantially the specificity and sensitivity of the model, as indicated by the ROC curves. Comparison to existing methods We compare the folded concave penalized learning scheme with both the Lasso penalized scheme and the principle component analysis-based feature selection (PCA) in the Parkinson’s biomarker identification problem that takes into account both the clinical features and MRI markers. The folded concave penalty method demonstrates a substantially better clinical potential than both the Lasso and PCA in terms of specificity and sensitivity. Conclusions For the first time, we applied the FCP learning method to MRI biomarker discovery in PD. The proposed approach successfully identified MRI markers that are clinically relevant. Combining these biomarkers with clinical features can substantially enhance performance. PMID:27102045

Rapid response oxygen-sensing nanofibers

PubMed Central

Xue, Ruipeng; Behera, Prajna; Viapiano, Mariano S.; Lannutti, John J.

2014-01-01

Molecular oxygen has profound effects on cell and tissue viability. Relevant sensor forms that can rapidly determine dissolved oxygen levels under biologically relevant conditions provide critical metabolic information. Using 0.5 μm diameter electrospun polycaprolactone (PCL) fiber containing an oxygen-sensitive probe, tris (4,7-diphenyl-1,10-phenanthroline) ruthenium(II) dichloride, we observed a response time of 0.9±0.12 seconds – 4–10 times faster than previous reports – while the t95 for the corresponding film was more than two orders of magnitude greater. Interestingly, the response and recovery times of slightly larger diameter PCL fibers were 1.79±0.23 s and 2.29±0.13 s, respectively, while the recovery time was not statistically different likely due to the more limited interactions of nitrogen with the polymer matrix. A more than 10-fold increase in PCL fiber diameter reduces oxygen sensitivity while having minor effects on response time; conversely, decreases in fiber diameter to less than 0.5 μm would likely decrease response times even further. In addition, a 50°C heat treatment of the electrospun fiber resulted in both increased Stern-Volmer slope and linearity likely due to secondary recrystallization that further homogenized the probe microenvironment. At exposure times up to 3600 s in length, photobleaching was observed but was largely eliminated by the use of either polyethersulfone (PES) or a PES-PCL core-shell composition. However, this resulted in 2- and 3-fold slower response times. Finally, even the non-core shell compositions containing the Ru oxygen probe result in no apparent cytotoxicity in representative glioblastoma cell populations. PMID:23706233

In-vitro Gd-DTPA Relaxometry Studies in Oxygenated Venous Human Blood and Aqueous Solution at 3 and 7T

PubMed Central

Kalavagunta, Chaitanya; Michaeli, Shalom; Metzger, Gregory J.

2014-01-01

In-vitro T1 and T2* relaxivities (r1 and r2*) of Gd-DTPA (GaD) in oxygenated human venous blood (OVB) and aqueous solution (AS) at 3T and 7T were calculated. GaD concentrations ([GaD]) in OVB and AS were prepared in the range 0–5 mM. All measurements were acquired at 37±2 °C. At both 3T and 7T, a linear relationship was observed between [GaD] and R1 in both AS and OVB. At 7T, r1 in AS decreased by 7.5% (p = 0.045) while there was a negligible change in OVB. With respect to R2*, a linear relationship with [GaD] was only observed in AS, while a more complex relationship was observed in OVB; quadratic below and linear above 2 mM at both field strengths. There was a significant increase of over four-fold in r2* with GaD in OVB at 7T (for [GaD] above 2mM, p ≪0.01) as compared to 3T. Furthermore, in comparison to r1, r2* in AS was less than two-fold higher at both field strengths while in OVB it was ~twenty-fold and ~ninety-fold higher at 3T and 7T, respectively. This observation emphasizes the importance of r2* knowledge at high magnetic fields, ≥3T. The comparison between r1 and r2* presented in this work is crucial in the design and optimization of high field MRI studies making use of paramagnetic contrast agents. This is especially true in multiple compartment systems such as blood where r2* dramatically increases while r1 remains relatively constant with increasing magnetic field strength. PMID:24523062

The Association between Nocturnal Cardiac Arrhythmias and Sleep-Disordered Breathing: The DREAM Study.

PubMed

Selim, Bernardo J; Koo, Brian B; Qin, Li; Jeon, Sangchoon; Won, Christine; Redeker, Nancy S; Lampert, Rachel J; Concato, John P; Bravata, Dawn M; Ferguson, Jared; Strohl, Kingman; Bennett, Adam; Zinchuk, Andrey; Yaggi, Henry K

2016-06-15

To determine whether sleep-disordered breathing (SDB) is associated with cardiac arrhythmia in a clinic-based population with multiple cardiovascular comorbidities and severe SDB. This was a cross-sectional analysis of 697 veterans who underwent polysomnography for suspected SDB. SDB was categorized according to the apnea-hypopnea index (AHI): none (AHI < 5), mild (5 ≥ AHI < 15), and moderate-severe (AHI ≥ 15). Nocturnal cardiac arrhythmias consisted of: (1) complex ventricular ectopy, (CVE: non-sustained ventricular tachycardia, bigeminy, trigeminy, or quadrigeminy), (2) combined supraventricular tachycardia, (CST: atrial fibrillation or supraventricular tachycardia), (3) intraventricular conduction delay (ICD), (4) tachyarrhythmias (ventricular and supraventricular), and (5) any cardiac arrhythmia. Unadjusted, adjusted logistic regression, and Cochran-Armitage testing examined the association between SDB and cardiac arrhythmias. Linear regression models explored the association between hypoxia, arousals, and cardiac arrhythmias. Compared to those without SDB, patients with moderate-severe SDB had almost three-fold unadjusted odds of any cardiac arrhythmia (2.94; CI 95%, 2.01-4.30; p < 0.0001), two-fold odds of tachyarrhythmias (2.16; CI 95%,1.47-3.18; p = 0.0011), two-fold odds of CVE (2.01; 1.36-2.96; p = 0.003), and two-fold odds of ICD (2.50; 1.58-3.95; p = 0.001). A linear trend was identified between SDB severity and all cardiac arrhythmia subtypes (p value linear trend < 0.0001). After adjusting for age, BMI, gender, and cardiovascular diseases, moderate-severe SDB patients had twice the odds of having nocturnal cardiac arrhythmias (2.24; 1.48-3.39; p = 0.004). Frequency of obstructive respiratory events and hypoxia were strong predictors of arrhythmia risk. SDB is independently associated with nocturnal cardiac arrhythmias. Increasing severity of SDB was associated with an increasing risk for any cardiac arrhythmia. © 2016 American Academy of Sleep Medicine.

Modeling time-dependent corrosion fatigue crack propagation in 7000 series aluminum alloys

NASA Technical Reports Server (NTRS)

Mason, Mark E.; Gangloff, Richard P.

1994-01-01

Stress corrosion cracking and corrosion fatigue experiments were conducted with the susceptible S-L orientation of AA7075-T651, immersed in acidified and inhibited NaCl solution, to provide a basis for incorporating environmental effects into fatigue crack propagation life prediction codes such as NASA FLAGRO. This environment enhances da/dN by five to ten-fold compared to fatigue in moist air. Time-based crack growth rates from quasi-static load experiments are an order of magnitude too small for accurate linear superposition prediction of da/dN for loading frequencies above 0.001 Hz. Alternate methods of establishing da/dt, based on rising-load or ripple-load-enhanced crack tip strain rate, do not increase da/dt and do not improve linear superposition. Corrosion fatigue is characterized by two regimes of frequency dependence; da/dN is proportional to f(exp -1) below 0.001 Hz and to F(exp 0) to F(exp -0.1) for higher frequencies. Da/dN increases mildly both with increasing hold-time at K(sub max) and with increasing rise-time for a range of loading waveforms. The mild time-dependence is due to cycle-time-dependent corrosion fatigue growth. This behavior is identical for S-L nd L-T crack orientations. The frequency response of environmental fatigue in several 7000 series alloys is variable and depends on undefined compositional or microstructural variables. Speculative explanations are based on the effect of Mg on occluded crack chemistry and embritting hydrogen uptake, or on variable hydrogen diffusion in the crack tip process zone. Cracking in the 7075/NaCl system is adequately described for life prediction by linear superposition for prolonged load-cycle periods, and by a time-dependent upper bound relationship between da/dN and delta K for moderate loading times.

Research on a high-precision calibration method for tunable lasers

NASA Astrophysics Data System (ADS)

Xiang, Na; Li, Zhengying; Gui, Xin; Wang, Fan; Hou, Yarong; Wang, Honghai

2018-03-01

Tunable lasers are widely used in the field of optical fiber sensing, but nonlinear tuning exists even for zero external disturbance and limits the accuracy of the demodulation. In this paper, a high-precision calibration method for tunable lasers is proposed. A comb filter is introduced and the real-time output wavelength and scanning rate of the laser are calibrated by linear fitting several time-frequency reference points obtained from it, while the beat signal generated by the auxiliary interferometer is interpolated and frequency multiplied to find more accurate zero crossing points, with these points being used as wavelength counters to resample the comb signal to correct the nonlinear effect, which ensures that the time-frequency reference points of the comb filter are linear. A stability experiment and a strain sensing experiment verify the calibration precision of this method. The experimental result shows that the stability and wavelength resolution of the FBG demodulation can reach 0.088 pm and 0.030 pm, respectively, using a tunable laser calibrated by the proposed method. We have also compared the demodulation accuracy in the presence or absence of the comb filter, with the result showing that the introduction of the comb filter results to a 15-fold wavelength resolution enhancement.

Border Collision and Smooth Bifurcations in a Family of Linear-Power Maps

NASA Astrophysics Data System (ADS)

Gardini, Laura; Makrooni, Roya

2016-02-01

In this work we describe some properties and bifurcations which occur in a family of linear-power maps typical in Nordmark’ systems. The continuous case has been investigated by many authors since a few years, while the discontinuous case has been considered only recently. In particular, having a vertical asymptote, it gives rise to new kinds of bifurcations. Organizing centers related to codimension-two bifurcation points, due to the intersection of a border collision bifurcation and a smooth fold bifurcation of cycles having a different symbolic sequence are evidenced. It is shown the relevant role played by a codimension-two point existing on any border collision bifurcation curve, and related to the smooth fold bifurcation of cycles with the same symbolic sequence. We recall some of the properties proved up to now, evidencing the rich structure which is still to be understood.

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

Controlled Folding, Motional, and Constitutional Dynamic Processes of Polyheterocyclic Molecular Strands.

PubMed

Barboiu, Mihail; Stadler, Adrian-Mihail; Lehn, Jean-Marie

2016-03-18

General design principles have been developed for the control of the structural features of polyheterocyclic strands and their effector-modulated shape changes. Induced defined molecular motions permit designed enforcement of helical as well as linear molecular shapes. The ability of such molecular strands to bind metal cations allows the generation of coiling/uncoiling processes between helically folded and extended linear states. Large molecular motions are produced on coordination of metal ions, which may be made reversible by competition with an ancillary complexing agent and fueled by sequential acid/base neutralization energy. The introduction of hydrazone units into the strands confers upon them constitutional dynamics, whereby interconversion between different strand compositions is achieved through component exchange. These features have relevance for nanomechanical devices. We present a morphological and functional analysis of such systems developed in our laboratories. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Development of a real-time wave field reconstruction TEM system (II): correction of coma aberration and 3-fold astigmatism, and real-time correction of 2-fold astigmatism.

PubMed

Tamura, Takahiro; Kimura, Yoshihide; Takai, Yoshizo

2018-02-01

In this study, a function for the correction of coma aberration, 3-fold astigmatism and real-time correction of 2-fold astigmatism was newly incorporated into a recently developed real-time wave field reconstruction TEM system. The aberration correction function was developed by modifying the image-processing software previously designed for auto focus tracking, as described in the first article of this series. Using the newly developed system, the coma aberration and 3-fold astigmatism were corrected using the aberration coefficients obtained experimentally before the processing was carried out. In this study, these aberration coefficients were estimated from an apparent 2-fold astigmatism induced under tilted-illumination conditions. In contrast, 2-fold astigmatism could be measured and corrected in real time from the reconstructed wave field. Here, the measurement precision for 2-fold astigmatism was found to be ±0.4 nm and ±2°. All of these aberration corrections, as well as auto focus tracking, were performed at a video frame rate of 1/30 s. Thus, the proposed novel system is promising for quantitative and reliable in situ observations, particularly in environmental TEM applications.

Direct Observation of Parallel Folding Pathways Revealed Using a Symmetric Repeat Protein System

PubMed Central

Aksel, Tural; Barrick, Doug

2014-01-01

Although progress has been made to determine the native fold of a polypeptide from its primary structure, the diversity of pathways that connect the unfolded and folded states has not been adequately explored. Theoretical and computational studies predict that proteins fold through parallel pathways on funneled energy landscapes, although experimental detection of pathway diversity has been challenging. Here, we exploit the high translational symmetry and the direct length variation afforded by linear repeat proteins to directly detect folding through parallel pathways. By comparing folding rates of consensus ankyrin repeat proteins (CARPs), we find a clear increase in folding rates with increasing size and repeat number, although the size of the transition states (estimated from denaturant sensitivity) remains unchanged. The increase in folding rate with chain length, as opposed to a decrease expected from typical models for globular proteins, is a clear demonstration of parallel pathways. This conclusion is not dependent on extensive curve-fitting or structural perturbation of protein structure. By globally fitting a simple parallel-Ising pathway model, we have directly measured nucleation and propagation rates in protein folding, and have quantified the fluxes along each path, providing a detailed energy landscape for folding. This finding of parallel pathways differs from results from kinetic studies of repeat-proteins composed of sequence-variable repeats, where modest repeat-to-repeat energy variation coalesces folding into a single, dominant channel. Thus, for globular proteins, which have much higher variation in local structure and topology, parallel pathways are expected to be the exception rather than the rule. PMID:24988356

Highly efficient and exact method for parallelization of grid-based algorithms and its implementation in DelPhi

PubMed Central

Li, Chuan; Li, Lin; Zhang, Jie; Alexov, Emil

2012-01-01

The Gauss-Seidel method is a standard iterative numerical method widely used to solve a system of equations and, in general, is more efficient comparing to other iterative methods, such as the Jacobi method. However, standard implementation of the Gauss-Seidel method restricts its utilization in parallel computing due to its requirement of using updated neighboring values (i.e., in current iteration) as soon as they are available. Here we report an efficient and exact (not requiring assumptions) method to parallelize iterations and to reduce the computational time as a linear/nearly linear function of the number of CPUs. In contrast to other existing solutions, our method does not require any assumptions and is equally applicable for solving linear and nonlinear equations. This approach is implemented in the DelPhi program, which is a finite difference Poisson-Boltzmann equation solver to model electrostatics in molecular biology. This development makes the iterative procedure on obtaining the electrostatic potential distribution in the parallelized DelPhi several folds faster than that in the serial code. Further we demonstrate the advantages of the new parallelized DelPhi by computing the electrostatic potential and the corresponding energies of large supramolecular structures. PMID:22674480

The instantaneous radial growth rate of stellar discs

NASA Astrophysics Data System (ADS)

Pezzulli, G.; Fraternali, F.; Boissier, S.; Muñoz-Mateos, J. C.

2015-08-01

We present a new and simple method to measure the instantaneous mass and radial growth rates of the stellar discs of spiral galaxies, based on their star formation rate surface density (SFRD) profiles. Under the hypothesis that discs are exponential with time-varying scalelengths, we derive a universal theoretical profile for the SFRD, with a linear dependence on two parameters: the specific mass growth rate ν _ M ≡ dot{M}_⋆ /M_⋆ and the specific radial growth rate ν _ R ≡ dot{R}_⋆ /R_⋆ of the disc. We test our theory on a sample of 35 nearby spiral galaxies, for which we derive a measurement of νM and νR. 32/35 galaxies show the signature of ongoing inside-out growth (νR > 0). The typical derived e-folding time-scales for mass and radial growth in our sample are ˜10 and ˜30 Gyr, respectively, with some systematic uncertainties. More massive discs have a larger scatter in νM and νR, biased towards a slower growth, both in mass and size. We find a linear relation between the two growth rates, indicating that our galaxy discs grow in size at ˜0.35 times the rate at which they grow in mass; this ratio is largely unaffected by systematics. Our results are in very good agreement with theoretical expectations if known scaling relations of disc galaxies are not evolving with time.

Sequestration of vacuum energy and the end of the universe.

PubMed

Kaloper, Nemanja; Padilla, Antonio

2015-03-13

Recently, we proposed a mechanism for sequestering the standard model vacuum energy that predicts that the Universe will collapse. Here we present a simple mechanism for bringing about this collapse, employing a scalar field whose potential is linear and becomes negative, providing the negative energy density required to end the expansion. The slope of the potential is chosen to allow for the expansion to last until the current Hubble time, about 10^{10} years, to accommodate our Universe. Crucially, this choice is technically natural due to a shift symmetry. Moreover, vacuum energy sequestering selects radiatively stable initial conditions for the collapse, which guarantee that immediately before the turnaround the Universe is dominated by the linear potential which drives an epoch of accelerated expansion for at least an e fold. Thus, a single, technically natural choice for the slope ensures that the collapse is imminent and is preceded by the current stage of cosmic acceleration, giving a new answer to the "why now?"

Paramagnetic fluorinated nanoemulsions for sensitive cellular fluorine-19 magnetic resonance imaging

PubMed Central

Kislukhin, Alexander A.; Xu, Hongyan; Adams, Stephen R.; Narsinh, Kazim H.; Tsien, Roger Y.; Ahrens, Eric T.

2016-01-01

Fluorine-19 magnetic resonance imaging (19F MRI) probes enable quantitative in vivo detection of cell therapies and inflammatory cells. Here, we describe the formulation of perfluorocarbon-based nanoemulsions with improved sensitivity for cellular MRI. Reduction of the 19F spin-lattice relaxation time (T1) enables rapid imaging and an improved signal-to-noise ratio, thereby improving cell detection sensitivity. We synthesized metal-binding β-diketones conjugated to linear perfluoropolyether (PFPE), formulated these fluorinated ligands as aqueous nanoemulsions, and then metalated them with various transition and lanthanide ions in the fluorous phase. Iron(III) tris-β-diketonate ('FETRIS') nanoemulsions with PFPE have low cytotoxicity (<20%) and superior MRI properties. Moreover, the 19F T1 can readily be reduced by an order of magnitude and tuned by stoichiometric modulation of the iron concentration. The resulting 19F MRI detection sensitivity is enhanced by 3-to-5 fold over previously used tracers at 11.7 T, and is predicted to increase by at least 8-fold at clinical field strength of 3 T. PMID:26974409

A novel isoflavone profiling method based on UPLC-PDA-ESI-MS.

PubMed

Zhang, Shuang; Zheng, Zong-Ping; Zeng, Mao-Mao; He, Zhi-Yong; Tao, Guan-Jun; Qin, Fang; Chen, Jie

2017-03-15

A novel non-targeted isoflavone profiling method was developed using the diagnostic fragment-ion-based extension strategy, based on ultra-high performance liquid chromatography coupled with photo-diode array detector and electrospray ionization-mass spectrometry (UPLC-PDA-ESI-MS). 16 types of isoflavones were obtained in positive mode, but only 12 were obtained in negative mode due to the absence of precursor ions. Malonyldaidzin and malonylgenistin glycosylated at the 4'-O position or malonylated at the 4″-O position of glucose were indicated by their retention behavior and fragmentation pattern. Three possible quantification methods in one run based on UPLC-PDA and UPLC-ESI-MS were validated and compared, suggesting that methods based on UPLC-ESI-MS possess remarkable selectivity and sensitivity. Impermissible quantitative deviations induced by the linearity calibration with 400-fold dynamic range was observed for the first time and was recalibrated with a 20-fold dynamic range. These results suggest that isoflavones and their stereoisomers can be simultaneously determined by positive-ion UPLC-ESI-MS in soymilk. Copyright © 2016. Published by Elsevier Ltd.

Analytical determination of flavonoids aimed to analysis of natural samples and active packaging applications.

PubMed

Castro-López, María del Mar; López-Vilariño, José Manuel; González-Rodríguez, María Victoria

2014-05-01

Several HPLC and UHPLC developed methods were compared to analyse the natural antioxidants catechins and quercetin used in active packaging and functional foods. Photodiode array detector coupled with a fluorescence detector and compared with LTQ-Orbitrap-MS was used. UHPLC was investigated as quick alternative without compromising the separation, analysis time shortened up to 6-fold. The feasibility of the four developed methods was compared. Linearity up to 0.9995, low detection limits (between 0.02 and 0.7 for HPLC-PDA, 2 to 7-fold lower for HPLC- LTQ-Orbitrap-MS and from 0.2 to 2mgL(-)(1) for UHPLC-PDA) and good precision parameters (RSD lower than 0.06%) were obtained. All methods were successfully applied to natural samples. LTQ-Orbitrap-MS allowed to identify other analytes of interest too. Good feasibility of the methods was also concluded from the analysis of catechin and quercetin release from new active packaging materials based on polypropylene added with catechins and green tea. Copyright © 2013 Elsevier Ltd. All rights reserved.

New Insights into the Folding of a β-Sheet Miniprotein in a Reduced Space of Collective Hydrogen Bond Variables: Application to a Hydrodynamic Analysis of the Folding Flow

PubMed Central

Kalgin, Igor V.; Caflisch, Amedeo; Chekmarev, Sergei F.; Karplus, Martin

2013-01-01

A new analysis of the 20 μs equilibrium folding/unfolding molecular dynamics simulations of the three-stranded antiparallel β-sheet miniprotein (beta3s) in implicit solvent is presented. The conformation space is reduced in dimensionality by introduction of linear combinations of hydrogen bond distances as the collective variables making use of a specially adapted Principal Component Analysis (PCA); i.e., to make structured conformations more pronounced, only the formed bonds are included in determining the principal components. It is shown that a three-dimensional (3D) subspace gives a meaningful representation of the folding behavior. The first component, to which eight native hydrogen bonds make the major contribution (four in each beta hairpin), is found to play the role of the reaction coordinate for the overall folding process, while the second and third components distinguish the structured conformations. The representative points of the trajectory in the 3D space are grouped into conformational clusters that correspond to locally stable conformations of beta3s identified in earlier work. A simplified kinetic network based on the three components is constructed and it is complemented by a hydrodynamic analysis. The latter, making use of “passive tracers” in 3D space, indicates that the folding flow is much more complex than suggested by the kinetic network. A 2D representation of streamlines shows there are vortices which correspond to repeated local rearrangement, not only around minima of the free energy surface, but also in flat regions between minima. The vortices revealed by the hydrodynamic analysis are apparently not evident in folding pathways generated by transition-path sampling. Making use of the fact that the values of the collective hydrogen bond variables are linearly related to the Cartesian coordinate space, the RMSD between clusters is determined. Interestingly, the transition rates show an approximate exponential correlation with distance in the hydrogen bond subspace. Comparison with the many published studies shows good agreement with the present analysis for the parts that can be compared, supporting the robust character of our understanding of this “hydrogen atom” of protein folding. PMID:23621790

Effect of anions or foods on absolute bioavailability of calcium from calcium salts in mice by pharmacokinetics.

PubMed

Ueda, Yukari; Taira, Zenei

2013-01-01

We studied the absolute bioavailability of calcium from calcium L-lactate in mice using pharmacokinetics, and reviewed the absolute bioavailability of calcium from three other calcium salts in mice previously studied: calcium chloride, calcium acetate, and calcium ascorbate. The results showed that calcium metabolism is linear between intravenous administration of 15 mg/kg and 30 mg/kg, and is not affected by anions. Results after oral calcium administration of 150 mg/kg showed that the intestinal absorption process was significantly different among the four calcium salts. The rank of absolute bioavailability of calcium was calcium ascorbate > calcium L-lactate ≥ calcium acetate > calcium chloride. The mean residence time (MRTab) of calcium from calcium ascorbate (32.2 minutes) in the intestinal tract was much longer than that from calcium L-lactate (9.5 minutes), calcium acetate (15.0 minutes) and calcium chloride (13.6 minutes). Furthermore, the foods di-D-fructo-furanose-1,2':2,3'-dianhydride, sudachi (Citrus sudachi) juice, and moromi-su (a Japanese vinegar) increased the absolute bioavailability of calcium from calcium chloride by 2.46-fold, 2.86-fold, and 1.23-fold, respectively, and prolonged MRTab by 48.5 minutes, 43.1 minutes, and 44.9 minutes, respectively. In conclusion, the prolonged MRTab of calcium in the intestinal tract by anion or food might cause the increased absorbability of calcium.

Carbon nanostructures modified LiFePO4 cathodes for lithium ion battery applications: optimized porosity and composition

NASA Astrophysics Data System (ADS)

Mahmoud, Lama; Singh Lalia, Boor; Hashaikeh, Raed

2016-12-01

Lithium iron phosphate (LiFePO4) battery cathode was fabricated without using any metallic current collector and polymeric binder. Carbon nanostructures (CNS) were used as microbinders for LiFePO4 particles and at the same time as a 3D current collector. A facile and cost effective method of fabricating composite cathodes of CNS and LiFePO4 was developed. Thick electrodes with high loading of active material (20-25 mg cm-2) were obtained that are almost 2-3 folds higher than commercial electrodes. SEM images confirm that the 3D CNS conductive network encapsulated the LiFePO4 particles homogenously facilitating the charge transfer at the electrode-CNS interface. The composition, scan rate and porosity of the paper-like cathode were sequentially varied and their influence was systematically monitored by means of linear sweep cyclic voltammetry and AC electrochemical impedance spectroscopy. Addition of CNS improved the electrode’s bulk electronic conductivity, mechanical integrity, surface area and double layer capacitance, yet compromised the charge transfer resistance at the electrode-electrolyte interface. Based on a range of the tested binder-free electrodes, this study proposes that electrodes with 20 wt% CNS having 49 ± 2.5% porosity had realized best improvements of two folds and four folds in the electronic conductivity and diffusion coefficient, respectively.

Phonation threshold pressure: Comparison of calculations and measurements taken with physical models of the vocal fold mucosa

PubMed Central

Fulcher, Lewis P.; Scherer, Ronald C.

2011-01-01

In an important paper on the physics of small amplitude oscillations, Titze showed that the essence of the vertical phase difference, which allows energy to be transferred from the flowing air to the motion of the vocal folds, could be captured in a surface wave model, and he derived a formula for the phonation threshold pressure with an explicit dependence on the geometrical and biomechanical properties of the vocal folds. The formula inspired a series of experiments [e.g., R. Chan and I. Titze, J. Acoust. Soc. Am 119, 2351–2362 (2006)]. Although the experiments support many aspects of Titze’s formula, including a linear dependence on the glottal half-width, the behavior of the experiments at the smallest values of this parameter is not consistent with the formula. It is shown that a key element for removing this discrepancy lies in a careful examination of the properties of the entrance loss coefficient. In particular, measurements of the entrance loss coefficient at small widths done with a physical model of the glottis (M5) show that this coefficient varies inversely with the glottal width. A numerical solution of the time-dependent equations of the surface wave model shows that adding a supraglottal vocal tract lowers the phonation threshold pressure by an amount approximately consistent with Chan and Titze’s experiments. PMID:21895097

Phonation threshold pressure: comparison of calculations and measurements taken with physical models of the vocal fold mucosa.

PubMed

Fulcher, Lewis P; Scherer, Ronald C

2011-09-01

In an important paper on the physics of small amplitude oscillations, Titze showed that the essence of the vertical phase difference, which allows energy to be transferred from the flowing air to the motion of the vocal folds, could be captured in a surface wave model, and he derived a formula for the phonation threshold pressure with an explicit dependence on the geometrical and biomechanical properties of the vocal folds. The formula inspired a series of experiments [e.g., R. Chan and I. Titze, J. Acoust. Soc. Am 119, 2351-2362 (2006)]. Although the experiments support many aspects of Titze's formula, including a linear dependence on the glottal half-width, the behavior of the experiments at the smallest values of this parameter is not consistent with the formula. It is shown that a key element for removing this discrepancy lies in a careful examination of the properties of the entrance loss coefficient. In particular, measurements of the entrance loss coefficient at small widths done with a physical model of the glottis (M5) show that this coefficient varies inversely with the glottal width. A numerical solution of the time-dependent equations of the surface wave model shows that adding a supraglottal vocal tract lowers the phonation threshold pressure by an amount approximately consistent with Chan and Titze's experiments. © 2011 Acoustical Society of America

Effect of anions or foods on absolute bioavailability of calcium from calcium salts in mice by pharmacokinetics

PubMed Central

Ueda, Yukari; Taira, Zenei

2013-01-01

We studied the absolute bioavailability of calcium from calcium L-lactate in mice using pharmacokinetics, and reviewed the absolute bioavailability of calcium from three other calcium salts in mice previously studied: calcium chloride, calcium acetate, and calcium ascorbate. The results showed that calcium metabolism is linear between intravenous administration of 15 mg/kg and 30 mg/kg, and is not affected by anions. Results after oral calcium administration of 150 mg/kg showed that the intestinal absorption process was significantly different among the four calcium salts. The rank of absolute bioavailability of calcium was calcium ascorbate > calcium L-lactate ≥ calcium acetate > calcium chloride. The mean residence time (MRTab) of calcium from calcium ascorbate (32.2 minutes) in the intestinal tract was much longer than that from calcium L-lactate (9.5 minutes), calcium acetate (15.0 minutes) and calcium chloride (13.6 minutes). Furthermore, the foods di-D-fructo-furanose-1,2′:2,3′-dianhydride, sudachi (Citrus sudachi) juice, and moromi-su (a Japanese vinegar) increased the absolute bioavailability of calcium from calcium chloride by 2.46-fold, 2.86-fold, and 1.23-fold, respectively, and prolonged MRTab by 48.5 minutes, 43.1 minutes, and 44.9 minutes, respectively. In conclusion, the prolonged MRTab of calcium in the intestinal tract by anion or food might cause the increased absorbability of calcium. PMID:27186137

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

How Fast is Collapse of Proteins During Folding?

NASA Astrophysics Data System (ADS)

Chahine, J.; Onuchic, J. N.; Socci, N. D.

1998-03-01

Recent experiments in fast folding proteins are now starting to address the question of how fast is collapse relative to the total folding time. Using minimalist models, we are able to investigate the way in which different scenarios of folding can arise depending on the interplay between the collapse order parameter and the order parameter sensitive to specific tertiary contacts. Most of our earlier studies have focused on the limit that collapse is very fast compared to the total folding time. In this work we focus on the opposite limit, i.e., at the folding temperature, collapse and folding occurs simultaneously. The folding mechanism becomes very different in this limit. Particularly, the non-specific collapse transition, that occurs at temperatures higher than the folding temperature for the fast collapse limit, now occurs between the folding and the glass temperature. We show how this transition can be identified and its consequences for the folding kinetics.

Quantification of change in vocal fold tissue stiffness relative to depth of artificial damage.

PubMed

Rohlfs, Anna-Katharina; Schmolke, Sebastian; Clauditz, Till; Hess, Markus; Müller, Frank; Püschel, Klaus; Roemer, Frank W; Schumacher, Udo; Goodyer, Eric

2017-10-01

To quantify changes in the biomechanical properties of human excised vocal folds with defined artificial damage. The linear skin rheometer (LSR) was used to obtain a series of rheological measurements of shear modulus from the surface of 30 human cadaver vocal folds. The tissue samples were initially measured in a native condition and then following varying intensities of thermal damage. Histological examination of each vocal fold was used to determine the depth of artificial alteration. The measured changes in stiffness were correlated with the depth of cell damage. For vocal folds in a pre-damage state the shear modulus values ranged from 537 Pa to 1,651 Pa (female) and from 583 Pa to 1,193 Pa (male). With increasing depth of damage from the intermediate layer of the lamina propria (LP), tissue stiffness increased consistently (compared with native values) following application of thermal damage to the vocal folds. The measurement showed an increase of tissue stiffness when the depth of tissue damage was extending from the intermediate LP layer downwards. Changes in the elastic characteristics of human vocal fold tissue following damage at defined depths were demonstrated in an in vitro experiment. In future, reproducible in vivo measurements of elastic vocal fold tissue alterations may enable phonosurgeons to infer the extent of subepithelial damage from changes in surface elasticity.

H-Bond Self-Assembly: Folding versus Duplex Formation.

PubMed

Núñez-Villanueva, Diego; Iadevaia, Giulia; Stross, Alexander E; Jinks, Michael A; Swain, Jonathan A; Hunter, Christopher A

2017-05-17

Linear oligomers equipped with complementary H-bond donor (D) and acceptor (A) sites can interact via intermolecular H-bonds to form duplexes or fold via intramolecular H-bonds. These competing equilibria have been quantified using NMR titration and dilution experiments for seven systems featuring different recognition sites and backbones. For all seven architectures, duplex formation is observed for homo-sequence 2-mers (AA·DD) where there are no competing folding equilibria. The corresponding hetero-sequence AD 2-mers also form duplexes, but the observed self-association constants are strongly affected by folding equilibria in the monomeric states. When the backbone is flexible (five or more rotatable bonds separating the recognition sites), intramolecular H-bonding is favored, and the folded state is highly populated. For these systems, the stability of the AD·AD duplex is 1-2 orders of magnitude lower than that of the corresponding AA·DD duplex. However, for three architectures which have more rigid backbones (fewer than five rotatable bonds), intramolecular interactions are not observed, and folding does not compete with duplex formation. These systems are promising candidates for the development of longer, mixed-sequence synthetic information molecules that show sequence-selective duplex formation.

Histologic and rheologic characterization of vocal fold scarring.

PubMed

Thibeault, Susan L; Gray, Steven D; Bless, Diane M; Chan, Roger W; Ford, Charles N

2002-03-01

Scarring of the vocal fold causes considerable dysphonia and presents significant treatment challenges. A rabbit model was developed to investigate the histologic ultrastructure and rheologic properties of the scarred vocal fold lamina propria. Eleven rabbit larynges were scarred by means of forcep biopsy. Sixty days postoperatively, the rabbits were sacrificed and their vocal folds were harvested. Histological analysis of the scarred and normal lamina propria was completed for collagen, procollagen, elastin, and hyaluronic acid. Linear viscoelastic shear properties of the tissues were also measured, including elastic shear modulus and dynamic viscosity. Compared to normal vocal fold lamina propria, scarred tissues demonstrated significantly less collagen, an increase in procollagen, and a decrease in elastin. Rheologically, both elastic shear modulus and dynamic viscosity were significantly higher for the scarred tissues. Increased stiffness and viscosity do not appear to result from an increase in collagen, but rather appear to be related to the presence of new, disorganized collagen scaffolding. Results are interpreted in terms of the possible role of interstitial proteins in the etiology of increased stiffness and viscosity, which requires further investigation. This animal model should allow for systematic future investigations of vocal fold scarring and its treatment.

Characteristics of phonation onset in a two-layer vocal fold model.

PubMed

Zhang, Zhaoyan

2009-02-01

Characteristics of phonation onset were investigated in a two-layer body-cover continuum model of the vocal folds as a function of the biomechanical and geometric properties of the vocal folds. The analysis showed that an increase in either the body or cover stiffness generally increased the phonation threshold pressure and phonation onset frequency, although the effectiveness of varying body or cover stiffness as a pitch control mechanism varied depending on the body-cover stiffness ratio. Increasing body-cover stiffness ratio reduced the vibration amplitude of the body layer, and the vocal fold motion was gradually restricted to the medial surface, resulting in more effective flow modulation and higher sound production efficiency. The fluid-structure interaction induced synchronization of more than one group of eigenmodes so that two or more eigenmodes may be simultaneously destabilized toward phonation onset. At certain conditions, a slight change in vocal fold stiffness or geometry may cause phonation onset to occur as eigenmode synchronization due to a different pair of eigenmodes, leading to sudden changes in phonation onset frequency, vocal fold vibration pattern, and sound production efficiency. Although observed in a linear stability analysis, a similar mechanism may also play a role in register changes at finite-amplitude oscillations.

The role of finite displacements in vocal fold modeling.

PubMed

Chang, Siyuan; Tian, Fang-Bao; Luo, Haoxiang; Doyle, James F; Rousseau, Bernard

2013-11-01

Human vocal folds experience flow-induced vibrations during phonation. In previous computational models, the vocal fold dynamics has been treated with linear elasticity theory in which both the strain and the displacement of the tissue are assumed to be infinitesimal (referred to as model I). The effect of the nonlinear strain, or geometric nonlinearity, caused by finite displacements is yet not clear. In this work, a two-dimensional model is used to study the effect of geometric nonlinearity (referred to as model II) on the vocal fold and the airflow. The result shows that even though the deformation is under 1 mm, i.e., less than 10% of the size of the vocal fold, the geometric nonlinear effect is still significant. Specifically, model I underpredicts the gap width, the flow rate, and the impact stress on the medial surfaces as compared to model II. The study further shows that the differences are caused by the contact mechanics and, more importantly, the fluid-structure interaction that magnifies the error from the small-displacement assumption. The results suggest that using the large-displacement formulation in a computational model would be more appropriate for accurate simulations of the vocal fold dynamics.

The "Knife-Cut Sign" Revisited: A Distinctive Presentation of Linear Erosive Herpes Simplex Virus Infection in Immunocompromised Patients.

PubMed

Cohen, Philip R

2015-10-01

The "knife-cut sign" is a distinctive presentation of linear erosive herpes simplex virus infection in immunocompromised patients. To describe a man whose herpes simplex virus infection-related skin lesions demonstrated the "knife-cut sign" and to review the characteristics of reported immunosuppressed individuals with "knife-cut" cutaneous herpes simplex virus lesions. A man with multiple myeloma and post-stem cell transplant cutaneous graft-versus-host disease managed with systemic prednisone and sirolimus developed disseminated cutaneous herpes simplex virus infection with virus-associated linear ulcers of the inguinal folds and the area between his ear and scalp; the lesions at both sites had a distinctive "knife-cut" appearance. Using the PubMed database, an extensive literature search was performed on herpes simplex virus, immunocompromised patient, and "knife-cut sign". Herpes simplex virus infection-associated skin lesions that demonstrate the "knife-cut sign" present in patients who are immunosuppressed secondary to either an underlying medical condition or a systemic therapy or both. The distinctive virus-related cutaneous lesions appear as linear ulcers and fissures in intertriginous areas, such as the folds in the inguinal area, the vulva, and the abdomen; in addition, other sites include beneath the breast, within the gluteal cleft, and the area between the ear and the scalp. Not only herpes simplex virus-2, but also herpes simplex virus-1 has been observed as the causative viral serotype; indeed, herpes simplex virus-1 has been associated with genital and inframammary lesions in addition to those above the neck. Direct fluorescent antibody testing is a rapid method for confirming the clinically suspected viral infection; however, since false-negative direct fluorescent antibody testing occurred in some of the patients, it may be prudent to also perform viral cultures and possibly lesional skin biopsies to establish the diagnosis. The herpes simplex virus infection-related skin lesions clinically improve once systemic antiviral therapy is initiated. In immunosuppressed individuals, the "knife-cut sign" is a distinctive presentation of cutaneous linear erosive herpes simplex virus infection. Recognition of the linear ulcers in intertriginous areas and body folds should prompt the clinician to consider herpes simplex virus infection-associated skin lesions in an immunocompromised patient and to initiate systemic antiviral treatment while awaiting the results of laboratory evaluation to confirm the suspected diagnosis.

Linearization improves the repeatability of quantitative dynamic contrast-enhanced MRI.

PubMed

Jones, Kyle M; Pagel, Mark D; Cárdenas-Rodríguez, Julio

2018-04-01

The purpose of this study was to compare the repeatabilities of the linear and nonlinear Tofts and reference region models (RRM) for dynamic contrast-enhanced MRI (DCE-MRI). Simulated and experimental DCE-MRI data from 12 rats with a flank tumor of C6 glioma acquired over three consecutive days were analyzed using four quantitative and semi-quantitative DCE-MRI metrics. The quantitative methods used were: 1) linear Tofts model (LTM), 2) non-linear Tofts model (NTM), 3) linear RRM (LRRM), and 4) non-linear RRM (NRRM). The following semi-quantitative metrics were used: 1) maximum enhancement ratio (MER), 2) time to peak (TTP), 3) initial area under the curve (iauc64), and 4) slope. LTM and NTM were used to estimate K trans , while LRRM and NRRM were used to estimate K trans relative to muscle (R Ktrans ). Repeatability was assessed by calculating the within-subject coefficient of variation (wSCV) and the percent intra-subject variation (iSV) determined with the Gage R&R analysis. The iSV for R Ktrans using LRRM was two-fold lower compared to NRRM at all simulated and experimental conditions. A similar trend was observed for the Tofts model, where LTM was at least 50% more repeatable than the NTM under all experimental and simulated conditions. The semi-quantitative metrics iauc64 and MER were as equally repeatable as K trans and R Ktrans estimated by LTM and LRRM respectively. The iSV for iauc64 and MER were significantly lower than the iSV for slope and TTP. In simulations and experimental results, linearization improves the repeatability of quantitative DCE-MRI by at least 30%, making it as repeatable as semi-quantitative metrics. Copyright © 2017 Elsevier Inc. All rights reserved.

Kinetic network study of the diversity and temperature dependence of Trp-Cage folding pathways: combining transition path theory with stochastic simulations.

PubMed

Zheng, Weihua; Gallicchio, Emilio; Deng, Nanjie; Andrec, Michael; Levy, Ronald M

2011-02-17

We present a new approach to study a multitude of folding pathways and different folding mechanisms for the 20-residue mini-protein Trp-Cage using the combined power of replica exchange molecular dynamics (REMD) simulations for conformational sampling, transition path theory (TPT) for constructing folding pathways, and stochastic simulations for sampling the pathways in a high dimensional structure space. REMD simulations of Trp-Cage with 16 replicas at temperatures between 270 and 566 K are carried out with an all-atom force field (OPLSAA) and an implicit solvent model (AGBNP). The conformations sampled from all temperatures are collected. They form a discretized state space that can be used to model the folding process. The equilibrium population for each state at a target temperature can be calculated using the weighted-histogram-analysis method (WHAM). By connecting states with similar structures and creating edges satisfying detailed balance conditions, we construct a kinetic network that preserves the equilibrium population distribution of the state space. After defining the folded and unfolded macrostates, committor probabilities (P(fold)) are calculated by solving a set of linear equations for each node in the network and pathways are extracted together with their fluxes using the TPT algorithm. By clustering the pathways into folding "tubes", a more physically meaningful picture of the diversity of folding routes emerges. Stochastic simulations are carried out on the network, and a procedure is developed to project sampled trajectories onto the folding tubes. The fluxes through the folding tubes calculated from the stochastic trajectories are in good agreement with the corresponding values obtained from the TPT analysis. The temperature dependence of the ensemble of Trp-Cage folding pathways is investigated. Above the folding temperature, a large number of diverse folding pathways with comparable fluxes flood the energy landscape. At low temperature, however, the folding transition is dominated by only a few localized pathways.

Polarization and Color Filtering Applied to Enhance Photogrammetric Measurements of Reflective Surfaces

NASA Technical Reports Server (NTRS)

Wells, Jeffrey M.; Jones, Thomas W.; Danehy, Paul M.

2005-01-01

Techniques for enhancing photogrammetric measurement of reflective surfaces by reducing noise were developed utilizing principles of light polarization. Signal selectivity with polarized light was also compared to signal selectivity using chromatic filters. Combining principles of linear cross polarization and color selectivity enhanced signal-to-noise ratios by as much as 800 fold. More typical improvements with combining polarization and color selectivity were about 100 fold. We review polarization-based techniques and present experimental results comparing the performance of traditional retroreflective targeting materials, cornercube targets returning depolarized light, and color selectivity.

There and back again: Two views on the protein folding puzzle.

PubMed

Finkelstein, Alexei V; Badretdin, Azat J; Galzitskaya, Oxana V; Ivankov, Dmitry N; Bogatyreva, Natalya S; Garbuzynskiy, Sergiy O

2017-07-01

The ability of protein chains to spontaneously form their spatial structures is a long-standing puzzle in molecular biology. Experimentally measured folding times of single-domain globular proteins range from microseconds to hours: the difference (10-11 orders of magnitude) is the same as that between the life span of a mosquito and the age of the universe. This review describes physical theories of rates of overcoming the free-energy barrier separating the natively folded (N) and unfolded (U) states of protein chains in both directions: "U-to-N" and "N-to-U". In the theory of protein folding rates a special role is played by the point of thermodynamic (and kinetic) equilibrium between the native and unfolded state of the chain; here, the theory obtains the simplest form. Paradoxically, a theoretical estimate of the folding time is easier to get from consideration of protein unfolding (the "N-to-U" transition) rather than folding, because it is easier to outline a good unfolding pathway of any structure than a good folding pathway that leads to the stable fold, which is yet unknown to the folding protein chain. And since the rates of direct and reverse reactions are equal at the equilibrium point (as follows from the physical "detailed balance" principle), the estimated folding time can be derived from the estimated unfolding time. Theoretical analysis of the "N-to-U" transition outlines the range of protein folding rates in a good agreement with experiment. Theoretical analysis of folding (the "U-to-N" transition), performed at the level of formation and assembly of protein secondary structures, outlines the upper limit of protein folding times (i.e., of the time of search for the most stable fold). Both theories come to essentially the same results; this is not a surprise, because they describe overcoming one and the same free-energy barrier, although the way to the top of this barrier from the side of the unfolded state is very different from the way from the side of the native state; and both theories agree with experiment. In addition, they predict the maximal size of protein domains that fold under solely thermodynamic (rather than kinetic) control and explain the observed maximal size of the "foldable" protein domains. Copyright © 2017 Elsevier B.V. All rights reserved.

There and back again: Two views on the protein folding puzzle

NASA Astrophysics Data System (ADS)

Finkelstein, Alexei V.; Badretdin, Azat J.; Galzitskaya, Oxana V.; Ivankov, Dmitry N.; Bogatyreva, Natalya S.; Garbuzynskiy, Sergiy O.

2017-07-01

The ability of protein chains to spontaneously form their spatial structures is a long-standing puzzle in molecular biology. Experimentally measured folding times of single-domain globular proteins range from microseconds to hours: the difference (10-11 orders of magnitude) is the same as that between the life span of a mosquito and the age of the universe. This review describes physical theories of rates of overcoming the free-energy barrier separating the natively folded (N) and unfolded (U) states of protein chains in both directions: ;U-to-N; and ;N-to-U;. In the theory of protein folding rates a special role is played by the point of thermodynamic (and kinetic) equilibrium between the native and unfolded state of the chain; here, the theory obtains the simplest form. Paradoxically, a theoretical estimate of the folding time is easier to get from consideration of protein unfolding (the ;N-to-U; transition) rather than folding, because it is easier to outline a good unfolding pathway of any structure than a good folding pathway that leads to the stable fold, which is yet unknown to the folding protein chain. And since the rates of direct and reverse reactions are equal at the equilibrium point (as follows from the physical ;detailed balance; principle), the estimated folding time can be derived from the estimated unfolding time. Theoretical analysis of the ;N-to-U; transition outlines the range of protein folding rates in a good agreement with experiment. Theoretical analysis of folding (the ;U-to-N; transition), performed at the level of formation and assembly of protein secondary structures, outlines the upper limit of protein folding times (i.e., of the time of search for the most stable fold). Both theories come to essentially the same results; this is not a surprise, because they describe overcoming one and the same free-energy barrier, although the way to the top of this barrier from the side of the unfolded state is very different from the way from the side of the native state; and both theories agree with experiment. In addition, they predict the maximal size of protein domains that fold under solely thermodynamic (rather than kinetic) control and explain the observed maximal size of the ;foldable; protein domains.

GPU-accelerated computation of electron transfer.

PubMed

Höfinger, Siegfried; Acocella, Angela; Pop, Sergiu C; Narumi, Tetsu; Yasuoka, Kenji; Beu, Titus; Zerbetto, Francesco

2012-11-05

Electron transfer is a fundamental process that can be studied with the help of computer simulation. The underlying quantum mechanical description renders the problem a computationally intensive application. In this study, we probe the graphics processing unit (GPU) for suitability to this type of problem. Time-critical components are identified via profiling of an existing implementation and several different variants are tested involving the GPU at increasing levels of abstraction. A publicly available library supporting basic linear algebra operations on the GPU turns out to accelerate the computation approximately 50-fold with minor dependence on actual problem size. The performance gain does not compromise numerical accuracy and is of significant value for practical purposes. Copyright © 2012 Wiley Periodicals, Inc.

[Feature extraction for breast cancer data based on geometric algebra theory and feature selection using differential evolution].

PubMed

Li, Jing; Hong, Wenxue

2014-12-01

The feature extraction and feature selection are the important issues in pattern recognition. Based on the geometric algebra representation of vector, a new feature extraction method using blade coefficient of geometric algebra was proposed in this study. At the same time, an improved differential evolution (DE) feature selection method was proposed to solve the elevated high dimension issue. The simple linear discriminant analysis was used as the classifier. The result of the 10-fold cross-validation (10 CV) classification of public breast cancer biomedical dataset was more than 96% and proved superior to that of the original features and traditional feature extraction method.

Analysis of photo linear elements, Laramie Mountains, Wyoming

NASA Technical Reports Server (NTRS)

Blackstone, D. L., Jr.

1973-01-01

The author has identified the following significant results. Photo linear features in the Precambrian rocks of the Laramie Mountains are delineated, and the azimuths plotted on rose diagrams. Three strike directions are dominant, two of which are in the northeast quadrant. Laramide folds in the Laramie basin to the west of the mountains appear to have the same trend, and apparently have been controlled by response of the basement along fractures such as have been measured from the imagery.

Rheometric properties of canine vocal fold tissues: Variation with anatomic location

PubMed Central

Kimura, Miwako; Mau, Ted; Chan, Roger W.

2010-01-01

Objective To evaluate the in vitro rheometric properties of the canine vocal fold lamina propria and muscle at phonatory frequencies, and their changes with anatomic location. Methods Six canine larynges were harvested immediately postmortem. Viscoelastic shear properties of anterior, middle, and posterior portions of the vocal fold cover (lamina propria) as well as those of the medial thyroarytenoid (TA) muscle (vocalis muscle) were quantified by a linear, controlled-strain simple-shear rheometer. Measurements of elastic shear modulus (G’) and dynamic viscosity (η’) of the specimens were conducted with small-amplitude sinusoidal shear deformation over a frequency range of 1 Hz to 250 Hz. Results All specimens showed similar frequency dependence of the viscoelastic functions, with G’ gradually increasing with frequency and η’ decreasing with frequency monotonically. G’ and η’ of the canine vocalis muscle were significantly higher than those of the canine vocal fold cover, and η’ of the canine vocal fold cover was significantly higher than that of the human vocal fold cover. There were no significant differences in G’ and in η’ between different portions of the canine vocal fold cover. Conclusion These preliminary data based on the canine model suggested that the vocalis muscle, while in a relaxed state in vitro, is significantly stiffer and more viscous than the vocal fold cover during vibration at phonatory frequencies. For large-amplitude vocal fold vibration involving the medial portion of the TA muscle, such distinct differences in viscoelastic properties of different layers of the vocal fold should be taken into account in multi-layered biomechanical models of phonation. PMID:21035291

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.

A mixed-effects model approach for the statistical analysis of vocal fold viscoelastic shear properties.

PubMed

Xu, Chet C; Chan, Roger W; Sun, Han; Zhan, Xiaowei

2017-11-01

A mixed-effects model approach was introduced in this study for the statistical analysis of rheological data of vocal fold tissues, in order to account for the data correlation caused by multiple measurements of each tissue sample across the test frequency range. Such data correlation had often been overlooked in previous studies in the past decades. The viscoelastic shear properties of the vocal fold lamina propria of two commonly used laryngeal research animal species (i.e. rabbit, porcine) were measured by a linear, controlled-strain simple-shear rheometer. Along with published canine and human rheological data, the vocal fold viscoelastic shear moduli of these animal species were compared to those of human over a frequency range of 1-250Hz using the mixed-effects models. Our results indicated that tissues of the rabbit, canine and porcine vocal fold lamina propria were significantly stiffer and more viscous than those of human. Mixed-effects models were shown to be able to more accurately analyze rheological data generated from repeated measurements. Copyright © 2017 Elsevier Ltd. All rights reserved.

Geology of the southwestern Pasco Basin

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

Not Available

1978-09-01

The objective of this study was to define those aspects of the stratigraphic, structural, and tectonic setting which are important to the integrity of a deep-mined waste-isolation cavern in the Columbia River basalts. Three principal structural features received the focus of the field effort in the 1,485-square-kilometer area. These are the northern end of the Horse Heaven uplift, the linear ridges of the Badger Mountain-Red Mountain trend, and the Rattlesnake uplift. The thickest sequence of basalt exposed in the study area is on the steep, northeastern slope of Rattlesnake Mountain; about 485 meters of stratigraphic section can be examined inmore » the field area. Subsidence and weak deformation of the southwestern Pasco Basin area during Yakima time can be recognized in the disposition of flows and interbeds. In the southwestern Pasco Basin, most of the topographically expressed basalt bedrock mountains, ridges, hills, and knolls have developed since spreading of the Saddle Mountains flows. Deformation since Ice Harbor time (about 8 million years ago) has been by folding, faulting, and in some structures, by a combination of both. The doubly plunging anticlinal folds of Badger Mountain, Red Mountain, and easternmost Rattlesnake Hills have vertical structural amplitudes in the 80 to 200-meter range. The high-angle, possibly reverse Badger Mountain fault has offset up to 60 meters; offset is downward on the northeast. Rattlesnake Mountain is, in part, a tilted fault-block structure. The western end of the Rattlesnake uplift, Rattlesnake Hills, is principally a broad anticline with numerous minor folds and faults. Geomorphic relations suggest that the post-Ice Harbor structural movement in the study area is of one episode. 65 figures, 8 tables.« less

General mechanism of two-state protein folding kinetics.

PubMed

Rollins, Geoffrey C; Dill, Ken A

2014-08-13

We describe here a general model of the kinetic mechanism of protein folding. In the Foldon Funnel Model, proteins fold in units of secondary structures, which form sequentially along the folding pathway, stabilized by tertiary interactions. The model predicts that the free energy landscape has a volcano shape, rather than a simple funnel, that folding is two-state (single-exponential) when secondary structures are intrinsically unstable, and that each structure along the folding path is a transition state for the previous structure. It shows how sequential pathways are consistent with multiple stochastic routes on funnel landscapes, and it gives good agreement with the 9 order of magnitude dependence of folding rates on protein size for a set of 93 proteins, at the same time it is consistent with the near independence of folding equilibrium constant on size. This model gives estimates of folding rates of proteomes, leading to a median folding time in Escherichia coli of about 5 s.

Kinetic Network Study of the Diversity and Temperature Dependence of Trp-Cage Folding Pathways: Combining Transition Path Theory with Stochastic Simulations

PubMed Central

Zheng, Weihua; Gallicchio, Emilio; Deng, Nanjie; Andrec, Michael; Levy, Ronald M.

2011-01-01

We present a new approach to study a multitude of folding pathways and different folding mechanisms for the 20-residue mini-protein Trp-Cage using the combined power of replica exchange molecular dynamics (REMD) simulations for conformational sampling, Transition Path Theory (TPT) for constructing folding pathways and stochastic simulations for sampling the pathways in a high dimensional structure space. REMD simulations of Trp-Cage with 16 replicas at temperatures between 270K and 566K are carried out with an all-atom force field (OPLSAA) and an implicit solvent model (AGBNP). The conformations sampled from all temperatures are collected. They form a discretized state space that can be used to model the folding process. The equilibrium population for each state at a target temperature can be calculated using the Weighted-Histogram-Analysis Method (WHAM). By connecting states with similar structures and creating edges satisfying detailed balance conditions, we construct a kinetic network that preserves the equilibrium population distribution of the state space. After defining the folded and unfolded macrostates, committor probabilities (Pfold) are calculated by solving a set of linear equations for each node in the network and pathways are extracted together with their fluxes using the TPT algorithm. By clustering the pathways into folding “tubes”, a more physically meaningful picture of the diversity of folding routes emerges. Stochastic simulations are carried out on the network and a procedure is developed to project sampled trajectories onto the folding tubes. The fluxes through the folding tubes calculated from the stochastic trajectories are in good agreement with the corresponding values obtained from the TPT analysis. The temperature dependence of the ensemble of Trp-Cage folding pathways is investigated. Above the folding temperature, a large number of diverse folding pathways with comparable fluxes flood the energy landscape. At low temperature, however, the folding transition is dominated by only a few localized pathways. PMID:21254767

Characterizing liquid redistribution in a biphasic vibrating vocal fold using finite element analysis.

PubMed

Kvit, Anton A; Devine, Erin E; Jiang, Jack J; Vamos, Andrew C; Tao, Chao

2015-05-01

Vocal fold tissue is biphasic and consists of a solid extracellular matrix skeleton swelled with interstitial fluid. Interactions between the liquid and solid impact the material properties and stress response of the tissue. The objective of this study was to model the movement of liquid during vocal fold vibration and to estimate the volume of liquid accumulation and stress experienced by the tissue near the anterior-posterior midline, where benign lesions are observed to form. A three-dimensional biphasic finite element model of a single vocal fold was built to solve for the liquid velocity, pore pressure, and von Mises stress during and just after vibration using the commercial finite element software COMSOL Multiphysics (Version 4.3a, 2013, Structural Mechanics and Subsurface Flow Modules). Vibration was induced by applying direct load pressures to the subglottal and intraglottal surfaces. Pressure ranges, frequency, and material parameters were chosen based on those reported in the literature. Postprocessing included liquid velocity, pore pressure, and von Mises stress calculations as well as the frequency-stress and amplitude-stress relationships. Resulting time-averaged velocity vectors during vibration indicated liquid movement toward the midline of the fold, as well as upward movement in the inferior-superior direction. Pore pressure and von Misses stresses were higher in this region just after vibration. A linear relationship was found between the amplitude and pore pressure, whereas a nonlinear relationship was found between the frequency and pore pressure. Although this study had certain computational simplifications, it is the first biphasic finite element model to use a realistic geometry and demonstrate the ability to characterize liquid movement due to vibration. Results indicate that there is a significant amount of liquid that accumulates at the midline; however, the role of this accumulation still requires investigation. Further investigation of these mechanical factors may lend insight into the mechanism of benign lesion formation. Copyright © 2015 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Characterizing liquid redistribution in a biphasic vibrating vocal fold using finite element analysis

PubMed Central

Kvit, Anton A.; Devine, Erin E.; Vamos, Andrew C.; Tao, Chao; Jiang, Jack J.

2015-01-01

OBJECTIVE Vocal fold tissue is biphasic and consists of a solid extracellular matric skeleton swelled with interstitial fluid. Interactions between the liquid and solid impact the material properties and stress response of the tissue. The objective of this study was to model the movement of liquid during vocal fold vibration and estimate the volume of liquid accumulation and stress experienced by the tissue near the anterior-posterior midline, where benign lesions are observed to form. METHODS A three-dimensional biphasic finite element model of a single vocal fold was built to solve for the liquid velocity, pore pressure, and von Mises stress during and just after vibration using the commercial finite element software COMSOL Multiphysics (Version 4.3a, 2013, Structural Mechanics and Subsurface Flow Modules). Vibration was induced by applying direct-load pressures to the subglottal and intraglottal surfaces. Pressure ranges, frequency and material parameters were chosen based on those reported in the literature. Post-processing included liquid velocity, pore pressure and von Mises stress calculations, as well as the frequency-stress and amplitude-stress relationships. RESULTS Resulting time-averaged velocity vectors during vibration indicated liquid movement towards the midline of the fold, as upwards movement in the inferior-superior direction. Pore pressure and von Misses stresses were higher in this region just following vibration. A linear relationship was found between the amplitude and pore pressure, while a nonlinear relationship was found between the frequency and pore pressure. CONCLUSIONS While this study had certain computational simplifications, it is the first biphasic finite element model to employ a realistic geometry and demonstrated the ability to characterize liquid movement due to vibration. Results indicate that there is a significant amount of liquid that accumulates at the midline, however the role of this accumulation still requires investigation. Further investigation of these mechanical factors may lend insight into the mechanism of benign lesion formation. PMID:25619469

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

Increasing the space-time product of super-resolution structured illumination microscopy by means of two-pattern illumination

NASA Astrophysics Data System (ADS)

Inochkin, F. M.; Pozzi, P.; Bezzubik, V. V.; Belashenkov, N. R.

2017-06-01

Superresolution image reconstruction method based on the structured illumination microscopy (SIM) principle with reduced and simplified pattern set is presented. The method described needs only 2 sinusoidal patterns shifted by half a period for each spatial direction of reconstruction, instead of the minimum of 3 for the previously known methods. The method is based on estimating redundant frequency components in the acquired set of modulated images. Digital processing is based on linear operations. When applied to several spatial orientations, the image set can be further reduced to a single pattern for each spatial orientation, complemented by a single non-modulated image for all the orientations. By utilizing this method for the case of two spatial orientations, the total input image set is reduced up to 3 images, providing up to 2-fold improvement in data acquisition time compared to the conventional 3-pattern SIM method. Using the simplified pattern design, the field of view can be doubled with the same number of spatial light modulator raster elements, resulting in a total 4-fold increase in the space-time product. The method requires precise knowledge of the optical transfer function (OTF). The key limitation is the thickness of object layer that scatters or emits light, which requires to be sufficiently small relatively to the lens depth of field. Numerical simulations and experimental results are presented. Experimental results are obtained on the SIM setup with the spatial light modulator based on the 1920x1080 digital micromirror device.

Co-evolutionary constraints of globular proteins correlate with their folding rates.

PubMed

Mallik, Saurav; Kundu, Sudip

2015-08-04

Folding rates (lnkf) of globular proteins correlate with their biophysical properties, but relationship between lnkf and patterns of sequence evolution remains elusive. We introduce 'relative co-evolution order' (rCEO) as length-normalized average primary chain separation of co-evolving pairs (CEPs), which negatively correlates with lnkf. In addition to pairs in native 3D contact, indirectly connected and structurally remote CEPs probably also play critical roles in protein folding. Correlation between rCEO and lnkf is stronger in multi-state proteins than two-state proteins, contrasting the case of contact order (co), where stronger correlation is found in two-state proteins. Finally, rCEO, co and lnkf are fitted into a 3D linear correlation. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

The Effects of the Menstrual Cycle on Vibratory Characteristics of the Vocal Folds Investigated With High-Speed Digital Imaging.

PubMed

Kunduk, Melda; Vansant, Mathew B; Ikuma, Takeshi; McWhorter, Andrew

2017-03-01

This study investigated the effect of menstrual cycle on vocal fold vibratory characteristics in young women using high-speed digital imaging. This study examined the menstrual phase effect on five objective high-speed imaging parameters and two self-rated perceptual parameters. The effects of oral birth control use were also investigated. Thirteen subjects with no prior voice complaints were included in this study. All data were collected at three different time periods (premenses, postmenses, ovulation) over the course of one menstrual cycle. For five of the 13 subjects, data were collected for two consecutive cycles. Six of 13 subjects were oral birth control users. From high-speed imaging data, five objective parameters were computed: fundamental frequency, fundamental frequency deviation, harmonics-to-noise ratio, harmonic richness factor, and ratio of first and second harmonics. They were supplemented by two self-rated parameters: Reflux Severity Index and perceptual voice quality rating. Analysis included mixed model linear analysis with repeated measures. Results indicated no significant main effects for menstrual phase, between-cycle, or birth control use in the analysis for mean fundamental frequency, fundamental frequency deviation, harmonics-to-noise ratio, harmonic richness factor, first and second harmonics, Reflux Severity Index, and perceptual voice quality rating. Additionally, there were no interaction effects. Hormone fluctuations observed across the menstrual cycle do not appear to have direct effect on vocal fold vibratory characteristics in young women with no voice concerns. Birth control use, on the other hand, may have influence on spectral richness of vocal fold vibration. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Electrodynamic pressure modulation of protein stability in cosolvents.

PubMed

Damodaran, Srinivasan

2013-11-19

Cosolvents affect structural stability of proteins in aqueous solutions. A clear understanding of the mechanism by which cosolvents impact protein stability is critical to understanding protein folding in a biological milieu. In this study, we investigated the Lifshitz-van der Waals dispersion interaction of seven different solutes with nine globular proteins and report that in an aqueous medium the structure-stabilizing solutes exert a positive electrodynamic pressure, whereas the structure-destabilizing solutes exert a negative electrodynamic pressure on the proteins. The net increase in the thermal denaturation temperature (ΔTd) of a protein in 1 M solution of various solutes was linearly related to the electrodynamic pressure (PvdW) between the solutes and the protein. The slope of the PvdW versus ΔTd plots was protein-dependent. However, we find a positive linear relationship (r(2) = 0.79) between the slope (i.e., d(ΔTd)/dPvdW) and the adiabatic compressibility (βs) of the proteins. Together, these results clearly indicate that the Lifshitz's dispersion forces are inextricably involved in solute-induced stabilization/destabilization of globular proteins. The positive and/or negative electrodynamic pressure generated by the solute-protein interaction across the water medium seems to be the fundamental mechanism by which solutes affect protein stability. This is at variance with the existing preferential hydration concept. The implication of these results is significant in the sense that, in addition to the hydrophobic effect that drives protein folding, the electrodynamic forces between the proteins and solutes in the biological milieu also might play a role in the folding process as well as in the stability of the folded state.

Prediction of area under the curve for a p-glycoprotein, a CYP3A4 and a CYP2C9 substrate using a single time point strategy: assessment using fexofenadine, itraconazole and losartan and metabolites.

PubMed

Srinivas, Nuggehally R

2016-01-01

In the present age of polypharmacy, limited sampling strategy becomes important to verify if drug levels are within the prescribed threshold limits from efficacy and safety considerations. The need to establish reliable single time concentration dependent models to predict exposure becomes important from cost and time perspectives. A simple unweighted linear regression model was developed to describe the relationship between Cmax versus AUC for fexofenadine, losartan, EXP3174, itraconazole and hydroxyitraconazole. The fold difference, defined as the quotient of the observed and predicted AUC values, were evaluated along with statistical comparison of the predicted versus observed values. The correlation between Cmax versus AUC was well established for all the five drugs with a correlation coefficient (r) ranging from 0.9130 to 0.9997. Majority of the predicted values for all the five drugs (77%) were contained within a narrow boundary of 0.75- to 1.5-fold difference. The r values for observed versus predicted AUC were 0.9653 (n = 145), 0.8342 (n = 76), 0.9524 (n = 88), 0.9339 (n = 89) and 0.9452 (n = 66) for fexofenadine, losartan, EXP3174, itraconazole and hydroxyitraconazole, respectively. Cmax versus AUC relationships were established for all drugs and were amenable for limited sampling strategy for AUC prediction. However, fexofenadine, EXP3174 and hydroxyitraconazole may be most relevant for AUC prediction by a single time concentration as judged by the various criteria applied in this study.

Controlling protein molecular dynamics: How to accelerate folding while preserving the native state

NASA Astrophysics Data System (ADS)

Jensen, Christian H.; Nerukh, Dmitry; Glen, Robert C.

2008-12-01

The dynamics of peptides and proteins generated by classical molecular dynamics (MD) is described by using a Markov model. The model is built by clustering the trajectory into conformational states and estimating transition probabilities between the states. Assuming that it is possible to influence the dynamics of the system by varying simulation parameters, we show how to use the Markov model to determine the parameter values that preserve the folded state of the protein and at the same time, reduce the folding time in the simulation. We investigate this by applying the method to two systems. The first system is an imaginary peptide described by given transition probabilities with a total folding time of 1μs. We find that only small changes in the transition probabilities are needed to accelerate (or decelerate) the folding. This implies that folding times for slowly folding peptides and proteins calculated using MD cannot be meaningfully compared to experimental results. The second system is a four residue peptide valine-proline-alanine-leucine in water. We control the dynamics of the transitions by varying the temperature and the atom masses. The simulation results show that it is possible to find the combinations of parameter values that accelerate the dynamics and at the same time preserve the native state of the peptide. A method for accelerating larger systems without performing simulations for the whole folding process is outlined.

Solvent friction changes the folding pathway of the tryptophan zipper TZ2.

PubMed

Narayanan, Ranjani; Pelakh, Leslie; Hagen, Stephen J

2009-07-17

Because the rate of a diffusional process such as protein folding is controlled by friction encountered along the reaction pathway, the speed of folding is readily tunable through adjustment of solvent viscosity. The precise relationship between solvent viscosity and the rate of diffusion is complex and even conformation-dependent, however, because both solvent friction and protein internal friction contribute to the total reaction friction. The heterogeneity of the reaction friction along the folding pathway may have subtle consequences. For proteins that fold on a multidimensional free-energy surface, an increase in solvent friction may drive a qualitative change in folding trajectory. Our time-resolved experiments on the rapidly and heterogeneously folding beta-hairpin TZ2 show a shift in the folding pathway as viscosity increases, even though the energetics of folding is unaltered. We also observe a nonlinear or saturating behavior of the folding relaxation time with rising solvent viscosity, potentially an experimental signature of the shifting pathway for unfolding. Our results show that manipulations of solvent viscosity in folding experiments and simulations may have subtle and unexpected consequences on the folding dynamics being studied.

Dependence of phonation threshold pressure on vocal tract acoustics and vocal fold tissue mechanics.

PubMed

Chan, Roger W; Titze, Ingo R

2006-04-01

Analytical and computer simulation studies have shown that the acoustic impedance of the vocal tract as well as the viscoelastic properties of vocal fold tissues are critical for determining the dynamics and the energy transfer mechanism of vocal fold oscillation. In the present study, a linear, small-amplitude oscillation theory was revised by taking into account the propagation of a mucosal wave and the inertive reactance (inertance) of the supraglottal vocal tract as the major energy transfer mechanisms for flow-induced self-oscillation of the vocal fold. Specifically, analytical results predicted that phonation threshold pressure (Pth) increases with the viscous shear properties of the vocal fold, but decreases with vocal tract inertance. This theory was empirically tested using a physical model of the larynx, where biological materials (fat, hyaluronic acid, and fibronectin) were implanted into the vocal fold cover to investigate the effect of vocal fold tissue viscoelasticity on Pth. A uniform-tube supraglottal vocal tract was also introduced to examine the effect of vocal tract inertance on Pth. Results showed that Pth decreased with the inertive impedance of the vocal tract and increased with the viscous shear modulus (G") or dynamic viscosity (eta') of the vocal fold cover, consistent with theoretical predictions. These findings supported the potential biomechanical benefits of hyaluronic acid as a surgical bioimplant for repairing voice disorders involving the superficial layer of the lamina propria, such as scarring, sulcus vocalis, atrophy, and Reinke's edema.

Heat capacity changes in RNA folding: application of perturbation theory to hammerhead ribozyme cold denaturation

PubMed Central

Mikulecky, Peter J.; Feig, Andrew L.

2004-01-01

In proteins, empirical correlations have shown that changes in heat capacity (ΔCP) scale linearly with the hydrophobic surface area buried upon folding. The influence of ΔCP on RNA folding has been widely overlooked and is poorly understood. In addition to considerations of solvent reorganization, electrostatic effects might contribute to ΔCPs of folding in polyanionic species such as RNAs. Here, we employ a perturbation method based on electrostatic theory to probe the hot and cold denaturation behavior of the hammerhead ribozyme. This treatment avoids much of the error associated with imposing two-state folding models on non-two-state systems. Ribozyme stability is perturbed across a matrix of solvent conditions by varying the concentration of NaCl and methanol co-solvent. Temperature-dependent unfolding is then monitored by circular dichroism spectroscopy. The resulting array of unfolding transitions can be used to calculate a ΔCP of folding that accurately predicts the observed cold denaturation temperature. We confirm the accuracy of the calculated ΔCP by using isothermal titration calorimetry, and also demonstrate a methanol-dependence of the ΔCP. We weigh the strengths and limitations of this method for determining ΔCP values. Finally, we discuss the data in light of the physical origins of the ΔCPs for RNA folding and consider their impact on biological function. PMID:15282329

A Computational Study of Vocal Fold Dehydration During Phonation.

PubMed

Wu, Liang; Zhang, Zhaoyan

2017-12-01

While vocal fold dehydration is often considered an important factor contributing to vocal fatigue, it still remains unclear whether vocal fold vibration alone is able to induce severe dehydration that has a noticeable effect on phonation and perceived vocal effort. A three-dimensional model was developed to investigate vocal fold systemic dehydration and surface dehydration during phonation. Based on the linear poroelastic theory, the model considered water resupply from blood vessels through the lateral boundary, water movement within the vocal folds, water exchange between the vocal folds and the surface liquid layer through the epithelium, and surface fluid accumulation and discharge to the glottal airway. Parametric studies were conducted to investigate water loss within the vocal folds and from the surface after a 5-min sustained phonation under different permeability and vibration conditions. The results showed that the dehydration generally increased with increasing vibration amplitude, increasing epithelial permeability, and reduced water resupply. With adequate water resupply, a large-amplitude vibration can induce an overall systemic dehydration as high as 3%. The distribution of water loss within the vocal folds was non-uniform, and a local dehydration higher than 5% was observed even under conditions of a low overall systemic dehydration (<1%). Such high level of water loss may severely affect tissue properties, muscular functions, and phonations characteristics. In contrast, water loss of the surface liquid layer was generally an order of magnitude higher than water loss inside the vocal folds, indicating that the surface dehydration level is likely not a good indicator of the systemic dehydration.

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.

Time-Varying Vocal Folds Vibration Detection Using a 24 GHz Portable Auditory Radar

PubMed Central

Hong, Hong; Zhao, Heng; Peng, Zhengyu; Li, Hui; Gu, Chen; Li, Changzhi; Zhu, Xiaohua

2016-01-01

Time-varying vocal folds vibration information is of crucial importance in speech processing, and the traditional devices to acquire speech signals are easily smeared by the high background noise and voice interference. In this paper, we present a non-acoustic way to capture the human vocal folds vibration using a 24-GHz portable auditory radar. Since the vocal folds vibration only reaches several millimeters, the high operating frequency and the 4 × 4 array antennas are applied to achieve the high sensitivity. The Variational Mode Decomposition (VMD) based algorithm is proposed to decompose the radar-detected auditory signal into a sequence of intrinsic modes firstly, and then, extract the time-varying vocal folds vibration frequency from the corresponding mode. Feasibility demonstration, evaluation, and comparison are conducted with tonal and non-tonal languages, and the low relative errors show a high consistency between the radar-detected auditory time-varying vocal folds vibration and acoustic fundamental frequency, except that the auditory radar significantly improves the frequency-resolving power. PMID:27483261

Time-Varying Vocal Folds Vibration Detection Using a 24 GHz Portable Auditory Radar.

PubMed

Hong, Hong; Zhao, Heng; Peng, Zhengyu; Li, Hui; Gu, Chen; Li, Changzhi; Zhu, Xiaohua

2016-07-28

Time-varying vocal folds vibration information is of crucial importance in speech processing, and the traditional devices to acquire speech signals are easily smeared by the high background noise and voice interference. In this paper, we present a non-acoustic way to capture the human vocal folds vibration using a 24-GHz portable auditory radar. Since the vocal folds vibration only reaches several millimeters, the high operating frequency and the 4 × 4 array antennas are applied to achieve the high sensitivity. The Variational Mode Decomposition (VMD) based algorithm is proposed to decompose the radar-detected auditory signal into a sequence of intrinsic modes firstly, and then, extract the time-varying vocal folds vibration frequency from the corresponding mode. Feasibility demonstration, evaluation, and comparison are conducted with tonal and non-tonal languages, and the low relative errors show a high consistency between the radar-detected auditory time-varying vocal folds vibration and acoustic fundamental frequency, except that the auditory radar significantly improves the frequency-resolving power.

General Mechanism of Two-State Protein Folding Kinetics

PubMed Central

Rollins, Geoffrey C.; Dill, Ken A.

2016-01-01

We describe here a general model of the kinetic mechanism of protein folding. In the Foldon Funnel Model, proteins fold in units of secondary structures, which form sequentially along the folding pathway, stabilized by tertiary interactions. The model predicts that the free energy landscape has a volcano shape, rather than a simple funnel, that folding is two-state (single-exponential) when secondary structures are intrinsically unstable, and that each structure along the folding path is a transition state for the previous structure. It shows how sequential pathways are consistent with multiple stochastic routes on funnel landscapes, and it gives good agreement with the 9 order of magnitude dependence of folding rates on protein size for a set of 93 proteins, at the same time it is consistent with the near independence of folding equilibrium constant on size. This model gives estimates of folding rates of proteomes, leading to a median folding time in Escherichia coli of about 5 s. PMID:25056406

Integration of Attributes from Non-Linear Characterization of Cardiovascular Time-Series for Prediction of Defibrillation Outcomes

PubMed Central

Shandilya, Sharad; Kurz, Michael C.; Ward, Kevin R.; Najarian, Kayvan

2016-01-01

Objective The timing of defibrillation is mostly at arbitrary intervals during cardio-pulmonary resuscitation (CPR), rather than during intervals when the out-of-hospital cardiac arrest (OOH-CA) patient is physiologically primed for successful countershock. Interruptions to CPR may negatively impact defibrillation success. Multiple defibrillations can be associated with decreased post-resuscitation myocardial function. We hypothesize that a more complete picture of the cardiovascular system can be gained through non-linear dynamics and integration of multiple physiologic measures from biomedical signals. Materials and Methods Retrospective analysis of 153 anonymized OOH-CA patients who received at least one defibrillation for ventricular fibrillation (VF) was undertaken. A machine learning model, termed Multiple Domain Integrative (MDI) model, was developed to predict defibrillation success. We explore the rationale for non-linear dynamics and statistically validate heuristics involved in feature extraction for model development. Performance of MDI is then compared to the amplitude spectrum area (AMSA) technique. Results 358 defibrillations were evaluated (218 unsuccessful and 140 successful). Non-linear properties (Lyapunov exponent > 0) of the ECG signals indicate a chaotic nature and validate the use of novel non-linear dynamic methods for feature extraction. Classification using MDI yielded ROC-AUC of 83.2% and accuracy of 78.8%, for the model built with ECG data only. Utilizing 10-fold cross-validation, at 80% specificity level, MDI (74% sensitivity) outperformed AMSA (53.6% sensitivity). At 90% specificity level, MDI had 68.4% sensitivity while AMSA had 43.3% sensitivity. Integrating available end-tidal carbon dioxide features into MDI, for the available 48 defibrillations, boosted ROC-AUC to 93.8% and accuracy to 83.3% at 80% sensitivity. Conclusion At clinically relevant sensitivity thresholds, the MDI provides improved performance as compared to AMSA, yielding fewer unsuccessful defibrillations. Addition of partial end-tidal carbon dioxide (PetCO2) signal improves accuracy and sensitivity of the MDI prediction model. PMID:26741805

Design of ET(B) receptor agonists: NMR spectroscopic and conformational studies of ET7-21[Leu7, Aib11, Cys(Acm)15].

PubMed

Hewage, Chandralal M; Jiang, Lu; Parkinson, John A; Ramage, Robert; Sadler, Ian H

2002-03-01

In a previous report we have shown that the endothelin-B receptor-selective linear endothelin peptide, ET-1[Cys (Acm)1,15, Ala3, Leu7, Aib11], folds into an alpha-helical conformation in a methanol-d3/water co-solvent [Hewage et al. (1998) FEBS Lett., 425, 234-238]. To study the requirements for the structure-activity relationships, truncated analogues of this peptide were subjected to further studies. Here we report the solution conformation of ET7-21[Leu7, Aib11, Cys(Acm)15], in a methanol-d3/water co-solvent at pH 3.6, by NMR spectroscopic and molecular modelling studies. Further truncation of this short peptide results in it displaying poor agonist activity. The modelled structure shows that the peptide folds into an alpha-helical conformation between residues Lys9-His16, whereas the C-terminus prefers no fixed conformation. This truncated linear endothelin analogue is pivotal for designing endothelin-B receptor agonists.

Prediction of atrial fibrillation recurrence after cardioversion-interaction analysis of cardiac autonomic regulation.

PubMed

Seeck, A; Rademacher, W; Fischer, C; Haueisen, J; Surber, R; Voss, A

2013-03-01

Today atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice accounting for approximately one third of hospitalizations and accompanied with a 5 fold increased risk for ischemic stroke and a 1.5 fold increased mortality risk. The role of the cardiac regulation system in AF recurrence after electrical cardioversion (CV) is still unclear. The aim of this study was to investigate the autonomic regulation by analyzing the interaction between heart rate and blood pressure using novel methods of nonlinear interaction dynamics, namely joint symbolic dynamics (JSD) and segmented Poincaré plot analysis (SPPA). For the first time, we applied SPPA to analyze the interaction between two time series. Introducing a parameter set of two indices, one derived from JSD and one from SPPA, the linear discriminant function analysis revealed an overall accuracy of 89% (sensitivity 91.7%, specificity 86.7%) for the classification between patients with stable sinus rhythm (group SR, n = 15) and with AF recurrence (group REZ, n = 12). This study proves that the assessment of the autonomic regulation by analyzing the coupling of heart rate and systolic blood pressure provides a potential tool for the prediction of AF recurrence after CV and could aid in the adjustment of therapeutic options for patients with AF. Copyright © 2012 IPEM. Published by Elsevier Ltd. All rights reserved.

Sublethal effects of four insecticides on folding and spinning behavior in the rice leaffolder, Cnaphalocrocis medinalis (Guenée) (Lepidoptera: Pyralidae).

PubMed

Yang, Yajun; Wang, Caiyun; Xu, Hongxing; Lu, Zhongxian

2018-03-01

The rice leaffolder, Cnaphalocrocis medinalis, is an important rice pest. The sublethal effects of chlorpyrifos, chlorantraniliprole, emamectin benzoate and spinosad were investigated on the folding and spinning behaviors of third- to fifth-instar C. medinalis larvae (L3 - L5) after insecticidal exposure of the second instar. A 25% lethal concentration (LC 25 ) of chlorpyrifos prolonged the leaf selection time of L5, and reduced the number of binds per primary fold for L4 and L5. An LC 10 of chlorantraniliprole reduced the number of binds per primary fold for L4 and increased the number of head swings per bind for L5. An LC 10 of emamectin benzoate shortened the primary fold length for L5 and decreased the number of head swings per primary fold for L3 and L4 and the number of head swings per bind for L3, while an LC 25 of emamectin benzoate shortened the fold length per 24 h for L5 and folding time for L3. An LC 10 of spinosad lowered the fold length per 24 h and the number of head swings for L5. An LC 25 of spinosad prolonged leaf selection time, and decreased primary fold length, binds per primary fold, binds per fold and fold length per 24 h in L5. Emamectin benzoate and spinosad exerted stronger sublethal effects on the folding and spinning behavior of C. medinalis than chlorpyrifos and chlorantraniliprole. These results provide better understanding of the sublethal effects of interactions of insecticides on C. medinalis. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Pressure-dependent refractive indices of gases by THz time-domain spectroscopy.

PubMed

Sang, Bark Hyeon; Jeon, Tea-In

2016-12-12

Noncontact terahertz time-domain spectroscopy was employed to measure pressure-dependent refractive indices of gases such as helium (He), argon (Ar), krypton (Kr), oxygen (O₂), nitrogen (N₂), methane (CH₄), and carbon dioxide (CO₂). The refractive indices of these gases scaled linearly with pressure, for pressures in the 55-3,750 torr range. At the highest pressure, the refractive indices ((n-1) x 10⁶) of He and CO₂ were 170 and 2,390, respectively. The refractive index of CO₂ was 14.1-fold higher than that of He, owing to the stronger polarizability of CO₂. Although the studied gases differed in terms of their molecular structure, their refractive indices were strongly determined by polarizability. The measured refractive indices agreed well with the theoretical calculations.

Direct multiplexed measurement of gene expression with color-coded probe pairs.

PubMed

Geiss, Gary K; Bumgarner, Roger E; Birditt, Brian; Dahl, Timothy; Dowidar, Naeem; Dunaway, Dwayne L; Fell, H Perry; Ferree, Sean; George, Renee D; Grogan, Tammy; James, Jeffrey J; Maysuria, Malini; Mitton, Jeffrey D; Oliveri, Paola; Osborn, Jennifer L; Peng, Tao; Ratcliffe, Amber L; Webster, Philippa J; Davidson, Eric H; Hood, Leroy; Dimitrov, Krassen

2008-03-01

We describe a technology, the NanoString nCounter gene expression system, which captures and counts individual mRNA transcripts. Advantages over existing platforms include direct measurement of mRNA expression levels without enzymatic reactions or bias, sensitivity coupled with high multiplex capability, and digital readout. Experiments performed on 509 human genes yielded a replicate correlation coefficient of 0.999, a detection limit between 0.1 fM and 0.5 fM, and a linear dynamic range of over 500-fold. Comparison of the NanoString nCounter gene expression system with microarrays and TaqMan PCR demonstrated that the nCounter system is more sensitive than microarrays and similar in sensitivity to real-time PCR. Finally, a comparison of transcript levels for 21 genes across seven samples measured by the nCounter system and SYBR Green real-time PCR demonstrated similar patterns of gene expression at all transcript levels.

CONDENSED MATTER: ELECTRONIC STRUCTURE, ELECTRICAL, MAGNETIC, AND OPTICAL PROPERTIES Magnetic Manipulation of Massless Dirac Fermions in Graphene Quantum Dot

NASA Astrophysics Data System (ADS)

Lin, Xin; Pan, Hui; Xu, Huai-Zhe

2010-12-01

We have theoretically analyzed the quasibound states in a graphene quantum dot (GQD) with a magnetic flux Φ in the centre. It is shown that the two-fold time reversal degeneracy is broken and the quasibound states of GQD with positive/negative angular momentum shifted upwards / downwards with increasing the magnetic flux. The variation of the quasibound energy depends linearly on the magnetic flux, which is quite different from the parabolic relationship for Schrödinger electrons. The GQD's quasibound states spectrum shows an obvious Aharonov—Bohm (AB) oscillations with the magnetic flux. It is also shown that the quasibound state with energy equal to the barrier height becomes a bound state completely confined in GQD.

Hybrid optical materials of plasmon-coupled CdSe/ZnS coreshells for photonic applications

PubMed Central

Seo, Jaetae; Fudala, Rafal; Kim, Wan-Joong; Rich, Ryan; Tabibi, Bagher; Cho, Hyoyeong; Gryczynski, Zygmunt; Gryczynski, Ignacy; Yu, William

2013-01-01

A hybrid optical nanostructure of plasmon-coupled SQDs was developed for photonic applications. The coupling distances between the mono-layers of Au nanoparticles with a surface concentration of ~9.18 × 10−4 nm−2 and CdSe/ZnS SQDs with that of ~3.7 × 10−3 nm−2 were controlled by PMMA plasma etching. Time-resolved spectroscopy of plasmon-coupled SQDs revealed a strong shortening of the longest lifetime and ~9-fold PL enhancement. Polarization-resolved PL spectroscopy displayed linear polarization and depolarization at near- and far-field plasmon-coupling, respectively. The physical origin of PL enhancement could be attributable to both the large local field enhancement and the fast resonant energy transfer. PMID:23457661

Fluid-acoustic interactions and their impact on pathological voiced speech

NASA Astrophysics Data System (ADS)

Erath, Byron D.; Zanartu, Matias; Peterson, Sean D.; Plesniak, Michael W.

2011-11-01

Voiced speech is produced by vibration of the vocal fold structures. Vocal fold dynamics arise from aerodynamic pressure loadings, tissue properties, and acoustic modulation of the driving pressures. Recent speech science advancements have produced a physiologically-realistic fluid flow solver (BLEAP) capable of prescribing asymmetric intraglottal flow attachment that can be easily assimilated into reduced order models of speech. The BLEAP flow solver is extended to incorporate acoustic loading and sound propagation in the vocal tract by implementing a wave reflection analog approach for sound propagation based on the governing BLEAP equations. This enhanced physiological description of the physics of voiced speech is implemented into a two-mass model of speech. The impact of fluid-acoustic interactions on vocal fold dynamics is elucidated for both normal and pathological speech through linear and nonlinear analysis techniques. Supported by NSF Grant CBET-1036280.

Folding dynamics of linear emulsion polymers into 3D architectures

NASA Astrophysics Data System (ADS)

McMullen, Angus; Bargteil, Dylan; Brujic, Jasna

Colloidal polymers have been limited to inflexible, solid colloids. Here we show that the fluidity of emulsion droplets allows for the self-assembly of flexible droplet chains, which can subsequently be folded into 3D structures via secondary interactions. We achieve this using DNA-guided interactions, to initially form the chain, and then program its folding pathways. When two emulsion droplets labeled with complementary DNA meet, the balance of hybridization energy and droplet deformation yields an equilibrium patch size. Therefore, the concentration of DNA on the surface determines the number of droplet-droplet bonds in the assembly. We find that 96 % of bound droplets successfully self-assemble into chains. Droplet binding is a stochastic process, following a Poisson distribution of lengths. Since the fluid droplets can rearrange, we compare the dynamics of emulsion chains to that of polymers. We also trigger secondary interactions along the chain, causing the formation of specific loops or compact clusters. This approach will allow us to fold our emulsion polymers into a wide array of soft structures, giving us a powerful biomimetic colloidal system to investigate protein folding on the mesoscopic scale. This work was supported by the NSF MRSEC Program (DMR-0820341).

Possible origin and significance of extension-parallel drainages in Arizona's metamophic core complexes

USGS Publications Warehouse

Spencer, J.E.

2000-01-01

The corrugated form of the Harcuvar, South Mountains, and Catalina metamorphic core complexes in Arizona reflects the shape of the middle Tertiary extensional detachment fault that projects over each complex. Corrugation axes are approximately parallel to the fault-displacement direction and to the footwall mylonitic lineation. The core complexes are locally incised by enigmatic, linear drainages that parallel corrugation axes and the inferred extension direction and are especially conspicuous on the crests of antiformal corrugations. These drainages have been attributed to erosional incision on a freshly denuded, planar, inclined fault ramp followed by folding that elevated and preserved some drainages on the crests of rising antiforms. According to this hypothesis, corrugations were produced by folding after subacrial exposure of detachment-fault foot-walls. An alternative hypothesis, proposed here, is as follows. In a setting where preexisting drainages cross an active normal fault, each fault-slip event will cut each drainage into two segments separated by a freshly denuded fault ramp. The upper and lower drainage segments will remain hydraulically linked after each fault-slip event if the drainage in the hanging-wall block is incised, even if the stream is on the flank of an antiformal corrugation and there is a large component of strike-slip fault movement. Maintenance of hydraulic linkage during sequential fault-slip events will guide the lengthening stream down the fault ramp as the ramp is uncovered, and stream incision will form a progressively lengthening, extension-parallel, linear drainage segment. This mechanism for linear drainage genesis is compatible with corrugations as original irregularities of the detachment fault, and does not require folding after early to middle Miocene footwall exhumations. This is desirable because many drainages are incised into nonmylonitic crystalline footwall rocks that were probably not folded under low-temperature, surface conditions. An alternative hypothesis, that drainages were localized by small fault grooves as footwalls were uncovered, is not supported by analysis of a down-plunge fault projection for the southern Rincon Mountains that shows a linear drainage aligned with the crest of a small antiformal groove on the detachment fault, but this process could have been effective elsewhere. Lineation-parallel drainages now plunge gently southwestward on the southwest ends of antiformal corrugations in the South and Buckskin Mountains, but these drainages must have originally plunged northeastward if they formed by either of the two alternative processes proposed here. Footwall exhumation and incision by northeast-flowing streams was apparently followed by core-complex arching and drainage reversal.

How Kinetics within the Unfolded State Affects Protein Folding: an Analysis Based on Markov State Models and an Ultra-Long MD Trajectory

PubMed Central

Deng, Nan-jie; Dai, Wei

2013-01-01

Understanding how kinetics in the unfolded state affects protein folding is a fundamentally important yet less well-understood issue. Here we employ three different models to analyze the unfolded landscape and folding kinetics of the miniprotein Trp-cage. The first is a 208 μs explicit solvent molecular dynamics (MD) simulation from D. E. Shaw Research containing tens of folding events. The second is a Markov state model (MSM-MD) constructed from the same ultra-long MD simulation; MSM-MD can be used to generate thousands of folding events. The third is a Markov state model built from temperature replica exchange MD simulations in implicit solvent (MSM-REMD). All the models exhibit multiple folding pathways, and there is a good correspondence between the folding pathways from direct MD and those computed from the MSMs. The unfolded populations interconvert rapidly between extended and collapsed conformations on time scales ≤ 40 ns, compared with the folding time of ≈ 5 μs. The folding rates are independent of where the folding is initiated from within the unfolded ensemble. About 90 % of the unfolded states are sampled within the first 40 μs of the ultra-long MD trajectory, which on average explores ~27 % of the unfolded state ensemble between consecutive folding events. We clustered the folding pathways according to structural similarity into “tubes”, and kinetically partitioned the unfolded state into populations that fold along different tubes. From our analysis of the simulations and a simple kinetic model, we find that when the mixing within the unfolded state is comparable to or faster than folding, the folding waiting times for all the folding tubes are similar and the folding kinetics is essentially single exponential despite the presence of heterogeneous folding paths with non-uniform barriers. When the mixing is much slower than folding, different unfolded populations fold independently leading to non-exponential kinetics. A kinetic partition of the Trp-cage unfolded state is constructed which reveals that different unfolded populations have almost the same probability to fold along any of the multiple folding paths. We are investigating whether the results for the kinetics in the unfolded state of the twenty-residue Trp-cage is representative of larger single domain proteins. PMID:23705683

Discovery of Linear Cyclotides in Monocot Plant Panicum laxum of Poaceae Family Provides New Insights into Evolution and Distribution of Cyclotides in Plants*

PubMed Central

Nguyen, Giang Kien Truc; Lian, Yilong; Pang, Edmund Weng Hou; Nguyen, Phuong Quoc Thuc; Tran, Tuan Dinh; Tam, James P.

2013-01-01

Cyclotides are disulfide-rich macrocyclic peptides that display a wide range of bioactivities and represent an important group of plant defense peptide biologics. A few linear variants of cyclotides have recently been identified. They share a high sequence homology with cyclotides but are biosynthetically unable to cyclize from their precursors. All hitherto reported cyclotides and their acyclic variants were isolated from dicot plants of the Rubiaceae, Violaceae, Cucurbitaceae, and recently the Fabaceae and Solanaceae families. Although several cyclotide-like genes in the Poaceae family were known from the data mining of the National Center for Biotechnology Information (NCBI) nucleotide database, their expression at the protein level has yet to be proven. Here, we report the discovery and characterization of nine novel linear cyclotides, designated as panitides L1–9, from the Panicum laxum of the Poaceae family and provide the first evidence of linear cyclotides at the protein level in a monocot plant. Disulfide mapping of panitide L3 showed that it possesses a cystine knot arrangement similar to cyclotides. Several panitides were shown to be active against Escherichia coli and cytotoxic to HeLa cells. They also displayed a high stability against heat and proteolytic degradation. Oxidative folding of the disulfide-reduced panitide L1 showed that it can fold efficiently into its native form. The presence of linear cyclotides in both dicots and monocots suggests their ancient origin and existence before the divergence of these two groups of flowering plants. Moreover, the Poaceae family contains many important food crops, and our discovery may open up new avenues of research using cyclotides and their acyclic variants in crop protection. PMID:23195955

Turning limited experimental information into 3D models of RNA.

PubMed

Flores, Samuel Coulbourn; Altman, Russ B

2010-09-01

Our understanding of RNA functions in the cell is evolving rapidly. As for proteins, the detailed three-dimensional (3D) structure of RNA is often key to understanding its function. Although crystallography and nuclear magnetic resonance (NMR) can determine the atomic coordinates of some RNA structures, many 3D structures present technical challenges that make these methods difficult to apply. The great flexibility of RNA, its charged backbone, dearth of specific surface features, and propensity for kinetic traps all conspire with its long folding time, to challenge in silico methods for physics-based folding. On the other hand, base-pairing interactions (either in runs to form helices or isolated tertiary contacts) and motifs are often available from relatively low-cost experiments or informatics analyses. We present RNABuilder, a novel code that uses internal coordinate mechanics to satisfy user-specified base pairing and steric forces under chemical constraints. The code recapitulates the topology and characteristic L-shape of tRNA and obtains an accurate noncrystallographic structure of the Tetrahymena ribozyme P4/P6 domain. The algorithm scales nearly linearly with molecule size, opening the door to the modeling of significantly larger structures.

A HPLC-UV method for the determination of puerarin in rat plasma after intravenous administration of PEGylated puerarin conjugate.

PubMed

Liu, Xinyi; Zhi, Hongying; Du, Feng; Ye, Zuguang; Wang, Naijie; Qin, Wenjie; Li, Jianrong

2010-12-01

A sensitive and reproducible HPLC method for quantitative determination of puerarin (PUE) in rat plasma was developed and validated using 4-hydroxybenzaldehyde as an internal standard. The separation of PUE was performed on a CAPCELL PAK C18 column by gradient elution with 0.2% aqueous phosphoric acid and acetonitrile as the mobile phase. The method was validated and found to be linear in the range of 80-12,000ng/mL. The limit of quantification was 80ng/mL based on 100μL of plasma. The variations for intra- and inter-day precision were less than 8.3%, and the accuracy values were between 98% and 105.2%. The extraction recoveries were more than 85%. The method was successfully applied in the comparative study of pharmacokinetics of PEGylated puerarin (PEG-PUE) versus PUE in rats. Compared with PUE, PEG-PUE showed a 5.2-fold increase in half-life of PUE and a 4.7-fold increase in mean residence time. In addition, this method was also successfully applied to determine the low plasma concentration of PUE regenerated from PEG-PUE in vitro. Copyright © 2010 Elsevier B.V. All rights reserved.

Strongly Cavity-Enhanced Spontaneous Emission from Silicon-Vacancy Centers in Diamond

DOE PAGES

Zhang, Jingyuan Linda; Sun, Shuo; Burek, Michael J.; ...

2018-01-29

Quantum emitters are an integral component for a broad range of quantum technologies, including quantum communication, quantum repeaters, and linear optical quantum computation. Solid-state color centers are promising candidates for scalable quantum optics due to their long coherence time and small inhomogeneous broadening. However, once excited, color centers often decay through phonon-assisted processes, limiting the efficiency of single-photon generation and photon-mediated entanglement generation. Herein, we demonstrate strong enhancement of spontaneous emission rate of a single silicon-vacancy center in diamond embedded within a monolithic optical cavity, reaching a regime in which the excited-state lifetime is dominated by spontaneous emission into themore » cavity mode. We observe 10-fold lifetime reduction and 42-fold enhancement in emission intensity when the cavity is tuned into resonance with the optical transition of a single silicon-vacancy center, corresponding to 90% of the excited-state energy decay occurring through spontaneous emission into the cavity mode. Here, we also demonstrate the largest coupling strength ( g/2π = 4.9 ± 0.3 GHz) and cooperativity ( C = 1.4) to date for color-center-based cavity quantum electrodynamics systems, bringing the system closer to the strong coupling regime.« less

Strongly Cavity-Enhanced Spontaneous Emission from Silicon-Vacancy Centers in Diamond

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

Zhang, Jingyuan Linda; Sun, Shuo; Burek, Michael J.

Quantum emitters are an integral component for a broad range of quantum technologies, including quantum communication, quantum repeaters, and linear optical quantum computation. Solid-state color centers are promising candidates for scalable quantum optics due to their long coherence time and small inhomogeneous broadening. However, once excited, color centers often decay through phonon-assisted processes, limiting the efficiency of single-photon generation and photon-mediated entanglement generation. Herein, we demonstrate strong enhancement of spontaneous emission rate of a single silicon-vacancy center in diamond embedded within a monolithic optical cavity, reaching a regime in which the excited-state lifetime is dominated by spontaneous emission into themore » cavity mode. We observe 10-fold lifetime reduction and 42-fold enhancement in emission intensity when the cavity is tuned into resonance with the optical transition of a single silicon-vacancy center, corresponding to 90% of the excited-state energy decay occurring through spontaneous emission into the cavity mode. Here, we also demonstrate the largest coupling strength ( g/2π = 4.9 ± 0.3 GHz) and cooperativity ( C = 1.4) to date for color-center-based cavity quantum electrodynamics systems, bringing the system closer to the strong coupling regime.« less

A kMC-MD method with generalized move-sets for the simulation of folding of α-helical and β-stranded peptides.

PubMed

Peter, Emanuel K; Pivkin, Igor V; Shea, Joan-Emma

2015-04-14

In Monte-Carlo simulations of protein folding, pathways and folding times depend on the appropriate choice of the Monte-Carlo move or process path. We developed a generalized set of process paths for a hybrid kinetic Monte Carlo-Molecular dynamics algorithm, which makes use of a novel constant time-update and allows formation of α-helical and β-stranded secondary structures. We apply our new algorithm to the folding of 3 different proteins: TrpCage, GB1, and TrpZip4. All three systems are seen to fold within the range of the experimental folding times. For the β-hairpins, we observe that loop formation is the rate-determining process followed by collapse and formation of the native core. Cluster analysis of both peptides reveals that GB1 folds with equal likelihood along a zipper or a hydrophobic collapse mechanism, while TrpZip4 follows primarily a zipper pathway. The difference observed in the folding behavior of the two proteins can be attributed to the different arrangements of their hydrophobic core, strongly packed, and dry in case of TrpZip4, and partially hydrated in the case of GB1.

Formation of dome and basin structures: Results from scaled experiments using non-linear rock analogues

NASA Astrophysics Data System (ADS)

Zulauf, J.; Zulauf, G.; Zanella, F.

2016-09-01

Dome and basin folds are structures with circular or slightly elongate outcrop patterns, which can form during single- and polyphase deformation in various tectonic settings. We used power-law viscous rock analogues to simulate single-phase dome-and-basin folding of rocks undergoing dislocation creep. The viscosity ratio between a single competent layer and incompetent matrix was 5, and the stress exponent of both materials was 7. The samples underwent layer-parallel shortening under bulk pure constriction. Increasing initial layer thickness resulted in a decrease in the number of domes and basins and an increase in amplitude, A, arc-length, L, wavelength, λ, and layer thickness, Hf. Samples deformed incrementally show progressive development of domes and basins until a strain of eY=Z = -30% is attained. During the dome-and-basin formation the layer thickened permanently, while A, L, and λ increased. A dominant wavelength was not attained. The normalized amplitude (A/λ) increased almost linearly reaching a maximum of 0.12 at eY=Z = -30%. During the last increment of shortening (eY=Z = -30 to -40%) the domes and basins did not further grow, but were overprinted by a second generation of non-cylindrical folds. Most of the geometrical parameters of the previously formed domes and basins behaved stable or decreased during this phase. The normalized arc-length (L/Hf) of domes and basins is significantly higher than that of 2D cylindrical folds. For this reason, the normalized arc length can probably be used to identify domes and basins in the field, even if these structures are not fully exposed in 3D.

Radical-induced purine lesion formation is dependent on DNA helical topology.

PubMed

Terzidis, Michael A; Prisecaru, Andreea; Molphy, Zara; Barron, Niall; Randazzo, Antonio; Dumont, Elise; Krokidis, Marios G; Kellett, Andrew; Chatgilialoglu, Chryssostomos

2016-11-01

Herein we report the quantification of purine lesions arising from gamma-radiation sourced hydroxyl radicals (HO • ) on tertiary dsDNA helical forms of supercoiled (SC), open circular (OC), and linear (L) conformation, along with single-stranded folded and non-folded sequences of guanine-rich DNA in selected G-quadruplex structures. We identify that DNA helical topology and folding plays major, and unexpected, roles in the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) and 8-oxo-7,8-dihydro-2'-deoxyadenosine (8-oxo-dA), along with tandem-type purine lesions 5',8-cyclo-2'-deoxyguanosine (5',8-cdG) and 5',8-cyclo-2'-deoxyadenosine (5',8-cdA). SC, OC, and L dsDNA conformers together with folded and non-folded G-quadruplexes d[TGGGGT] 4 (TG4T), d[AGGG(TTAGGG) 3 ] (Tel22), and the mutated tel24 d[TTGGG(TTAGGG) 3 A] (mutTel24) were exposed to HO • radicals and purine lesions were then quantified via stable isotope dilution LC-MS/MS analysis. Purine oxidation in dsDNA follows L > OC ≫ SC indicating greater damage towards the extended B-DNA topology. Conversely, G-quadruplex sequences were significantly more resistant toward purine oxidation in their unfolded states as compared with G-tetrad folded topologies; this effect is confirmed upon comparative analysis of Tel22 (∼50% solution folded) and mutTel24 (∼90% solution folded). In an effort to identify the accessibly of hydroxyl radicals to quadruplex purine nucleobases, G-quadruplex solvent cavities were then modeled at 1.33 Å with evidence suggesting that folded G-tetrads may act as potential oxidant traps to protect against chromosomal DNA damage.

A computational study on convolutional feature combination strategies for grade classification in colon cancer using fluorescence microscopy data

NASA Astrophysics Data System (ADS)

Chowdhury, Aritra; Sevinsky, Christopher J.; Santamaria-Pang, Alberto; Yener, Bülent

2017-03-01

The cancer diagnostic workflow is typically performed by highly specialized and trained pathologists, for which analysis is expensive both in terms of time and money. This work focuses on grade classification in colon cancer. The analysis is performed over 3 protein markers; namely E-cadherin, beta actin and colagenIV. In addition, we also use a virtual Hematoxylin and Eosin (HE) stain. This study involves a comparison of various ways in which we can manipulate the information over the 4 different images of the tissue samples and come up with a coherent and unified response based on the data at our disposal. Pre- trained convolutional neural networks (CNNs) is the method of choice for feature extraction. The AlexNet architecture trained on the ImageNet database is used for this purpose. We extract a 4096 dimensional feature vector corresponding to the 6th layer in the network. Linear SVM is used to classify the data. The information from the 4 different images pertaining to a particular tissue sample; are combined using the following techniques: soft voting, hard voting, multiplication, addition, linear combination, concatenation and multi-channel feature extraction. We observe that we obtain better results in general than when we use a linear combination of the feature representations. We use 5-fold cross validation to perform the experiments. The best results are obtained when the various features are linearly combined together resulting in a mean accuracy of 91.27%.

Vastly accelerated linear least-squares fitting with numerical optimization for dual-input delay-compensated quantitative liver perfusion mapping.

PubMed

Jafari, Ramin; Chhabra, Shalini; Prince, Martin R; Wang, Yi; Spincemaille, Pascal

2018-04-01

To propose an efficient algorithm to perform dual input compartment modeling for generating perfusion maps in the liver. We implemented whole field-of-view linear least squares (LLS) to fit a delay-compensated dual-input single-compartment model to very high temporal resolution (four frames per second) contrast-enhanced 3D liver data, to calculate kinetic parameter maps. Using simulated data and experimental data in healthy subjects and patients, whole-field LLS was compared with the conventional voxel-wise nonlinear least-squares (NLLS) approach in terms of accuracy, performance, and computation time. Simulations showed good agreement between LLS and NLLS for a range of kinetic parameters. The whole-field LLS method allowed generating liver perfusion maps approximately 160-fold faster than voxel-wise NLLS, while obtaining similar perfusion parameters. Delay-compensated dual-input liver perfusion analysis using whole-field LLS allows generating perfusion maps with a considerable speedup compared with conventional voxel-wise NLLS fitting. Magn Reson Med 79:2415-2421, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Microbial Transformation of Esters of Chlorinated Carboxylic Acids

PubMed Central

Paris, D. F.; Wolfe, N. L.; Steen, W. C.

1984-01-01

Two groups of compounds were selected for microbial transformation studies. In the first group were carboxylic acid esters having a fixed aromatic moiety and an increasing length of the alkyl component. Ethyl esters of chlorine-substituted carboxylic acids were in the second group. Microorganisms from environmental waters and a pure culture of Pseudomonas putida U were used. The bacterial populations were monitored by plate counts, and disappearance of the parent compound was followed by gas-liquid chromatography as a function of time. The products of microbial hydrolysis were the respective carboxylic acids. Octanol-water partition coefficients (Kow) for the compounds were measured. These values spanned three orders of magnitude, whereas microbial transformation rate constants (kb) varied only 50-fold. The microbial rate constants of the carboxylic acid esters with a fixed aromatic moiety increased with an increasing length of alkyl substituents. The regression coefficient for the linear relationships between log kb and log Kow was high for group 1 compounds, indicating that these parameters correlated well. The regression coefficient for the linear relationships for group 2 compounds, however, was low, indicating that these parameters correlated poorly. PMID:16346459

Effects of desolvation barriers and sidechains on local-nonlocal coupling and chevron behaviors in coarse-grained models of protein folding.

PubMed

Chen, Tao; Chan, Hue Sun

2014-04-14

Local-nonlocal coupling is an organizational principle in protein folding. It envisions a cooperative energetic interplay between local conformational preferences and favorable nonlocal contacts. Previous theoretical studies by our group showed that two classes of native-centric coarse-grained models can capture the experimentally observed high degrees of protein folding cooperativity and diversity in folding rates. These models either embody an explicit local-nonlocal coupling mechanism or incorporate desolvation barriers in the models' pairwise interactions. Here a conceptual connection is made between these two paradigmatic coarse-grained interaction schemes by showing that desolvation barriers enhance local-nonlocal coupling. Furthermore, we find that a class of coarse-grained protein models with a single-site representation of sidechains also increases local-nonlocal coupling relative to mainchain models without sidechains. Enhanced local-nonlocal coupling generally leads to higher folding cooperativity and chevron plots with more linear folding arms. For the sidechain models studied, the chevron plot simulated with entirely native-centric intrachain interactions behaves very similarly to the corresponding chevron plots simulated with interactions that are partly modulated by sequence- and denaturant-dependent transfer free energies. In these essentially native-centric models, the mild chevron rollovers in the simulated folding arm are caused by occasionally populated intermediates as well as the movement of the unfolded and putative folding transition states. The strength and limitation of the models are analyzed by comparison with experiment. New formulations of sidechain models that may provide a physical account for nonnative interactions are also explored.

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.

Predictor variables for half marathon race time in recreational female runners

PubMed Central

Knechtle, Beat; Knechtle, Patrizia; Barandun, Ursula; Rosemann, Thomas; Lepers, Romuald

2011-01-01

INTRODUCTION: The relationship between skin-fold thickness and running performance has been investigated from 100 m to the marathon distance, except the half marathon distance. OBJECTIVE: To investigate whether anthropometry characteristics or training practices were related to race time in 42 recreational female half marathoners to determine the predictor variables of half-marathon race time and to inform future novice female half marathoners. METHODS: Observational field study at the ‘Half Marathon Basel’ in Switzerland. RESULTS: In the bivariate analysis, body mass (r = 0.60), body mass index (r = 0.48), body fat (r = 0.56), skin-fold at pectoral (r = 0.61), mid-axilla (r = 0.69), triceps (r = 0.49), subscapular (r = 0.61), abdominal (r = 0.59), suprailiac (r = 0.55) medial calf (r = 0.53) site, and speed of the training sessions (r = -0.68) correlated to race time. Mid-axilla skin-fold (p = 0.04) and speed of the training sessions (p = 0.0001) remained significant after multi-variate analysis. Race time in a half marathon might be predicted by the following equation (r2 = 0.71): Race time (min)  =  166.7 + 1.7x (mid-axilla skin-fold, mm) - 6.4x (speed in training, km/h). Running speed during training was related to skin-fold thickness at mid-axilla (r = -0.31), subscapular (r = -0.38), abdominal (r = -0.44), suprailiacal (r = -0.41), the sum of eight skin-folds (r = -0.36) and percent body fat (r = -0.31). CONCLUSION: Anthropometric and training variables were related to half-marathon race time in recreational female runners. Skin-fold thicknesses at various upper body locations were related to training intensity. High running speed in training appears to be important for fast half-marathon race times and may reduce upper body skin-fold thicknesses in recreational female half marathoners. PMID:21484048

Predictor variables for half marathon race time in recreational female runners.

PubMed

Knechtle, Beat; Knechtle, Patrizia; Barandun, Ursula; Rosemann, Thomas; Lepers, Romuald

2011-01-01

The relationship between skin-fold thickness and running performance has been investigated from 100 m to the marathon distance, except the half marathon distance. To investigate whether anthropometry characteristics or training practices were related to race time in 42 recreational female half marathoners to determine the predictor variables of half-marathon race time and to inform future novice female half marathoners. Observational field study at the 'Half Marathon Basel' in Switzerland. In the bivariate analysis, body mass (r = 0.60), body mass index (r = 0.48), body fat (r = 0.56), skin-fold at pectoral (r = 0.61), mid-axilla (r = 0.69), triceps (r = 0.49), subscapular (r = 0.61), abdominal (r = 0.59), suprailiac (r = 0.55) medial calf (r = 0.53) site, and speed of the training sessions (r = -0.68) correlated to race time. Mid-axilla skin-fold (p = 0.04) and speed of the training sessions (p = 0.0001) remained significant after multi-variate analysis. Race time in a half marathon might be predicted by the following equation (r² = 0.71): Race time (min) = 166.7 + 1.7x (mid-axilla skin-fold, mm) - 6.4x (speed in training, km/h). Running speed during training was related to skinfold thickness at mid-axilla (r = -0.31), subscapular (r = -0.38), abdominal (r = -0.44), suprailiacal (r = -0.41), the sum of eight skin-folds (r = -0.36) and percent body fat (r = -0.31). Anthropometric and training variables were related to half-marathon race time in recreational female runners. Skin-fold thicknesses at various upper body locations were related to training intensity. High running speed in training appears to be important for fast half-marathon race times and may reduce upper body skin-fold thicknesses in recreational female half marathoners.

New Structural and Functional Contexts of the Dx[DN]xDG Linear Motif: Insights into Evolution of Calcium-Binding Proteins

PubMed Central

Rigden, Daniel J.; Woodhead, Duncan D.; Wong, Prudence W. H.; Galperin, Michael Y.

2011-01-01

Binding of calcium ions (Ca2+) to proteins can have profound effects on their structure and function. Common roles of calcium binding include structure stabilization and regulation of activity. It is known that diverse families – EF-hands being one of at least twelve – use a Dx[DN]xDG linear motif to bind calcium in near-identical fashion. Here, four novel structural contexts for the motif are described. Existing experimental data for one of them, a thermophilic archaeal subtilisin, demonstrate for the first time a role for Dx[DN]xDG-bound calcium in protein folding. An integrin-like embedding of the motif in the blade of a β-propeller fold – here named the calcium blade – is discovered in structures of bacterial and fungal proteins. Furthermore, sensitive database searches suggest a common origin for the calcium blade in β-propeller structures of different sizes and a pan-kingdom distribution of these proteins. Factors favouring the multiple convergent evolution of the motif appear to include its general Asp-richness, the regular spacing of the Asp residues and the fact that change of Asp into Gly and vice versa can occur though a single nucleotide change. Among the known structural contexts for the Dx[DN]xDG motif, only the calcium blade and the EF-hand are currently found intracellularly in large numbers, perhaps because the higher extracellular concentration of Ca2+ allows for easier fixing of newly evolved motifs that have acquired useful functions. The analysis presented here will inform ongoing efforts toward prediction of similar calcium-binding motifs from sequence information alone. PMID:21720552

Folding time dependence of the motions of a molecular motor in an amorphous medium

NASA Astrophysics Data System (ADS)

Ciobotarescu, Simona; Bechelli, Solene; Rajonson, Gabriel; Migirditch, Samuel; Hester, Brooke; Hurduc, Nicolae; Teboul, Victor

2017-12-01

We investigate the dependence of the displacements of a molecular motor embedded inside a glassy material on its folding characteristic time τf. We observe two different time regimes. For slow foldings (regime I) the diffusion evolves very slowly with τf, while for rapid foldings (regime II) the diffusion increases strongly with τf(D ≈τf-2 ), suggesting two different physical mechanisms. We find that in regime I the motor's displacement during the folding process is counteracted by a reverse displacement during the unfolding, while in regime II this counteraction is much weaker. We notice that regime I behavior is reminiscent of the scallop theorem that holds for larger motors in a continuous medium. We find that the difference in the efficiency of the motor's motion explains most of the observed difference between the two regimes. For fast foldings the motor trajectories differ significantly from the opposite trajectories induced by the following unfolding process, resulting in a more efficient global motion than for slow foldings. This result agrees with the fluctuation theorems expectation for time reversal mechanisms. In agreement with the fluctuation theorems we find that the motors are unexpectedly more efficient when they are generating more entropy, a result that can be used to increase dramatically the motor's motion.

Sex differences in association of race performance, skin-fold thicknesses, and training variables for recreational half-marathon runners.

PubMed

Knechtle, Beat; Knechtle, Patrizia; Rosemann, Thomas; Senn, Oliver

2010-12-01

The purpose of this study was to investigate the association between selected skin-fold thicknesses and training variables with a half-marathon race time, for both male and female recreational runners, using bi- and multivariate analysis. In 52 men, two skin-fold thicknesses (abdominal and calf) were significantly and positively correlated with race time; whereas in 15 women, five (pectoral, mid-axilla, subscapular, abdominal, and suprailiac) showed positive and significant relations with total race time. In men, the mean weekly running distance, minimum distance run per week, maximum distance run per week, mean weekly hours of running, number of running training sessions per week, and mean speed of the training sessions were significantly and negatively related to total race time, but not in women. Interaction analyses suggested that race time was more strongly associated with anthropometry in women than men. Race time for the women was independently associated with the sum of eight skin-folds; but for the men, only the mean speed during training sessions was independently associated. Skin-fold thicknesses and training variables in these groups were differently related to race time according to their sex.

Human telomere sequence DNA in water-free and high-viscosity solvents: G-quadruplex folding governed by Kramers rate theory.

PubMed

Lannan, Ford M; Mamajanov, Irena; Hud, Nicholas V

2012-09-19

Structures formed by human telomere sequence (HTS) DNA are of interest due to the implication of telomeres in the aging process and cancer. We present studies of HTS DNA folding in an anhydrous, high viscosity deep eutectic solvent (DES) comprised of choline choride and urea. In this solvent, the HTS DNA forms a G-quadruplex with the parallel-stranded ("propeller") fold, consistent with observations that reduced water activity favors the parallel fold, whereas alternative folds are favored at high water activity. Surprisingly, adoption of the parallel structure by HTS DNA in the DES, after thermal denaturation and quick cooling to room temperature, requires several months, as opposed to less than 2 min in an aqueous solution. This extended folding time in the DES is, in part, due to HTS DNA becoming kinetically trapped in a folded state that is apparently not accessed in lower viscosity solvents. A comparison of times required for the G-quadruplex to convert from its aqueous-preferred folded state to its parallel fold also reveals a dependence on solvent viscosity that is consistent with Kramers rate theory, which predicts that diffusion-controlled transitions will slow proportionally with solvent friction. These results provide an enhanced view of a G-quadruplex folding funnel and highlight the necessity to consider solvent viscosity in studies of G-quadruplex formation in vitro and in vivo. Additionally, the solvents and analyses presented here should prove valuable for understanding the folding of many other nucleic acids and potentially have applications in DNA-based nanotechnology where time-dependent structures are desired.

Testing Taylor’s hypothesis in Amazonian rainfall fields during the WETAMC/LBA experiment

NASA Astrophysics Data System (ADS)

Poveda, Germán; Zuluaga, Manuel D.

2005-11-01

Taylor's hypothesis (TH) for rainfall fields states that the spatial correlation of rainfall intensity at two points at the same instant of time can be equated with the temporal correlation at two instants of time at some fixed location. The validity of TH is tested in a set of 12 storms developed in Rondonia, southwestern Amazonia, Brazil, during the January-February 1999 Wet Season Atmospheric Meso-scale Campaign. The time Eulerian and Lagrangian Autocorrelation Functions (ACF) are estimated, as well as the time-averaged space ACF, using radar rainfall rates of storms spanning between 3.2 and 23 h, measured at 7-10-min time resolution, over a circle of 100 km radius, at 2 km spatial resolution. TH does not hold in 9 out of the 12 studied storms, due to their erratic trajectories and very low values of zonal wind velocity at 700 hPa, independently from underlying atmospheric stability conditions. TH was shown to hold for 3 storms, up to a cutoff time scale of 10-15 min, which is closely related to observed features of the life cycle of convective cells in the region. Such cutoff time scale in Amazonian storms is much shorter than the 40 min identified in mid-latitude convective storms, due to much higher values of CAPE and smaller values of storm speed in Amazonian storms as compared to mid-latitude ones, which in turn contribute to a faster destruction of the rainfall field isotropy. Storms satisfying TH undergo smooth linear trajectories over space, and exhibit the highest negative values of maximum, mean and minimum zonal wind velocity at 700 hPa, within narrow ranges of atmospheric stability conditions. Non-dimensional parameters involving CAPE (maximum, mean and minimum) and CINE (mean) are identified during the storms life cycle, for which TH holds: CAPE mean/CINE mean = [30-35], CAPE max/CINE mean = [32-40], and CAPE min/CINE mean = [22-28]. These findings are independent upon the timing of storms within the diurnal cycle. Also, the estimated Eulerian time ACF's decay faster than the time-averaged space and the Lagrangian time ACF's, irrespectively of TH validity. The Eulerian ACF's exhibit shorter e-folding times, reflecting smaller correlations over short time scales, but also shorter scale of fluctuation, reflecting less persistence in time than over space. No significant associations (linear, exponential or power law) were found between estimated e-folding times and scale of fluctuation, with all estimates of CAPE and CINE. Secondary correlation maxima appear between 50 and 70 min in the Lagrangian time ACF's for storms satisfying TH. No differences were found in the behavior of each of the three ACF's for storms developed during either the Easterly or Westerly zonal wind regimes which characterize the development of meso-scale convective systems over the region. These results have important implications for modelling and downscaling rainfall fields over tropical land areas.

SAAFEC: Predicting the Effect of Single Point Mutations on Protein Folding Free Energy Using a Knowledge-Modified MM/PBSA Approach.

PubMed

Getov, Ivan; Petukh, Marharyta; Alexov, Emil

2016-04-07

Folding free energy is an important biophysical characteristic of proteins that reflects the overall stability of the 3D structure of macromolecules. Changes in the amino acid sequence, naturally occurring or made in vitro, may affect the stability of the corresponding protein and thus could be associated with disease. Several approaches that predict the changes of the folding free energy caused by mutations have been proposed, but there is no method that is clearly superior to the others. The optimal goal is not only to accurately predict the folding free energy changes, but also to characterize the structural changes induced by mutations and the physical nature of the predicted folding free energy changes. Here we report a new method to predict the Single Amino Acid Folding free Energy Changes (SAAFEC) based on a knowledge-modified Molecular Mechanics Poisson-Boltzmann (MM/PBSA) approach. The method is comprised of two main components: a MM/PBSA component and a set of knowledge based terms delivered from a statistical study of the biophysical characteristics of proteins. The predictor utilizes a multiple linear regression model with weighted coefficients of various terms optimized against a set of experimental data. The aforementioned approach yields a correlation coefficient of 0.65 when benchmarked against 983 cases from 42 proteins in the ProTherm database. the webserver can be accessed via http://compbio.clemson.edu/SAAFEC/.

Shear properties of vocal fold mucosal tissues and their effect on vocal fold oscillation

NASA Astrophysics Data System (ADS)

Chan, Roger Wai Kai

Viscoelastic shear properties of vocal fold mucosal tissues and phonosurgical biomaterials were measured with a parallel-plate rotational rheometer. Elastic, viscous and damping properties were quantified as a function of frequency (0.01 Hz to 15 Hz) for human vocal fold mucosal tissues (N = 15), implantable biomaterials commonly used in the treatment of vocal fold paralysis (Teflon, gelatin, and collagen) (the non-mucosal group), and biomaterials currently or potentially useful in the treatment of vocal fold mucosal defects (adipose tissue or fat, hyaluronic acid, and fibronectin) (the mucosal group). It was found that intersubject differences as large as an order of magnitude were often observed for the shear properties of vocal fold mucosal tissues, part of which may be age- and gender-related. Shear properties of the non-mucosal group biomaterials were often much higher than those of the mucosal group biomaterials, which were relatively close to the shear properties of mucosal tissues. Viscoelastic and rheological modeling showed that shear properties of human vocal fold mucosa may be described by a quasi-linear viscoelastic theory and a statistical network theory, based upon which extrapolations to audio frequencies were possible. A theory of small-amplitude vocal fold oscillation was revisited to describe the effects of tissue shear properties on vocal fold oscillation and phonation threshold pressure, a measure of the 'ease' of phonation and an objective indication of vocal function. It was found that phonation threshold pressure is directly related to the viscous shear modulus or the 'effective damping modulus', a concept proposed to quantify the effective amount of damping in vocal fold oscillation. The mucosal group biomaterials were incorporated into the artificial vocal fold mucosa of a physical model in order to empirically assess their effects on phonation threshold pressure. Results showed that higher threshold pressures were consistently observed for higher concentrations of hyaluronic acid and for hyaluronic acid mixed with fibronectin, in correlation with their differences in viscous shear modulus and effective damping modulus. Implications for phonosurgery were discussed in terms of the choice of optimal biomaterials for the surgical management of vocal fold mucosal defects and lamina propria deficiencies.

Artificial Intelligence vs. Statistical Modeling and Optimization of Continuous Bead Milling Process for Bacterial Cell Lysis.

PubMed

Haque, Shafiul; Khan, Saif; Wahid, Mohd; Dar, Sajad A; Soni, Nipunjot; Mandal, Raju K; Singh, Vineeta; Tiwari, Dileep; Lohani, Mohtashim; Areeshi, Mohammed Y; Govender, Thavendran; Kruger, Hendrik G; Jawed, Arshad

2016-01-01

For a commercially viable recombinant intracellular protein production process, efficient cell lysis and protein release is a major bottleneck. The recovery of recombinant protein, cholesterol oxidase (COD) was studied in a continuous bead milling process. A full factorial response surface methodology (RSM) design was employed and compared to artificial neural networks coupled with genetic algorithm (ANN-GA). Significant process variables, cell slurry feed rate (A), bead load (B), cell load (C), and run time (D), were investigated and optimized for maximizing COD recovery. RSM predicted an optimum of feed rate of 310.73 mL/h, bead loading of 79.9% (v/v), cell loading OD 600 nm of 74, and run time of 29.9 min with a recovery of ~3.2 g/L. ANN-GA predicted a maximum COD recovery of ~3.5 g/L at an optimum feed rate (mL/h): 258.08, bead loading (%, v/v): 80%, cell loading (OD 600 nm ): 73.99, and run time of 32 min. An overall 3.7-fold increase in productivity is obtained when compared to a batch process. Optimization and comparison of statistical vs. artificial intelligence techniques in continuous bead milling process has been attempted for the very first time in our study. We were able to successfully represent the complex non-linear multivariable dependence of enzyme recovery on bead milling parameters. The quadratic second order response functions are not flexible enough to represent such complex non-linear dependence. ANN being a summation function of multiple layers are capable to represent complex non-linear dependence of variables in this case; enzyme recovery as a function of bead milling parameters. Since GA can even optimize discontinuous functions present study cites a perfect example of using machine learning (ANN) in combination with evolutionary optimization (GA) for representing undefined biological functions which is the case for common industrial processes involving biological moieties.

Artificial Intelligence vs. Statistical Modeling and Optimization of Continuous Bead Milling Process for Bacterial Cell Lysis

PubMed Central

Haque, Shafiul; Khan, Saif; Wahid, Mohd; Dar, Sajad A.; Soni, Nipunjot; Mandal, Raju K.; Singh, Vineeta; Tiwari, Dileep; Lohani, Mohtashim; Areeshi, Mohammed Y.; Govender, Thavendran; Kruger, Hendrik G.; Jawed, Arshad

2016-01-01

For a commercially viable recombinant intracellular protein production process, efficient cell lysis and protein release is a major bottleneck. The recovery of recombinant protein, cholesterol oxidase (COD) was studied in a continuous bead milling process. A full factorial response surface methodology (RSM) design was employed and compared to artificial neural networks coupled with genetic algorithm (ANN-GA). Significant process variables, cell slurry feed rate (A), bead load (B), cell load (C), and run time (D), were investigated and optimized for maximizing COD recovery. RSM predicted an optimum of feed rate of 310.73 mL/h, bead loading of 79.9% (v/v), cell loading OD600 nm of 74, and run time of 29.9 min with a recovery of ~3.2 g/L. ANN-GA predicted a maximum COD recovery of ~3.5 g/L at an optimum feed rate (mL/h): 258.08, bead loading (%, v/v): 80%, cell loading (OD600 nm): 73.99, and run time of 32 min. An overall 3.7-fold increase in productivity is obtained when compared to a batch process. Optimization and comparison of statistical vs. artificial intelligence techniques in continuous bead milling process has been attempted for the very first time in our study. We were able to successfully represent the complex non-linear multivariable dependence of enzyme recovery on bead milling parameters. The quadratic second order response functions are not flexible enough to represent such complex non-linear dependence. ANN being a summation function of multiple layers are capable to represent complex non-linear dependence of variables in this case; enzyme recovery as a function of bead milling parameters. Since GA can even optimize discontinuous functions present study cites a perfect example of using machine learning (ANN) in combination with evolutionary optimization (GA) for representing undefined biological functions which is the case for common industrial processes involving biological moieties. PMID:27920762

The ALE Discontinuous Galerkin Method for the Simulatio of Air Flow Through Pulsating Human Vocal Folds

NASA Astrophysics Data System (ADS)

Feistauer, Miloslav; Kučera, Václav; Prokopová, Jaroslav; Horáček, Jaromír

2010-09-01

The aim of this work is the simulation of viscous compressible flows in human vocal folds during phonation. The computational domain is a bounded subset of IR2, whose geometry mimics the shape of the human larynx. During phonation, parts of the solid impermeable walls are moving in a prescribed manner, thus simulating the opening and closing of the vocal chords. As the governing equations we take the compressible Navier-Stokes equations in ALE form. Space semidiscretization is carried out by the discontinuous Galerkin method combined with a linearized semi-implicit approach. Numerical experiments are performed with the resulting scheme.

A Study of the Structure-Activity Relationship of GABAA-Benzodiazepine Receptor Bivalent Ligands by Conformational Analysis with Low Temperature NMR and X-ray Analysis

PubMed Central

Han, Dongmei; Försterling, F. Holger; Li, Xiaoyan; Deschamps, Jeffrey R.; Parrish, Damon; Cao, Hui; Rallapalli, Sundari; Clayton, Terry; Teng, Yun; Majumder, Samarpan; Sankar, Subramaniam; Roth, Bryan L.; Sieghart, Werner; Furtmuller, Roman; Rowlett, James; Weed, Mike R.; Cook, James M.

2013-01-01

The stable conformations of GABAA-benzodiazepine receptor bivalent ligands were determined by low temperature NMR spectroscopy and confirmed by single crystal X-ray analysis. The stable conformations in solution correlated well with those in the solid state. The linear conformation was important for these dimers to access the binding site and exhibit potent in vitro affinity and was illustrated for α5 subtype selective ligands. Bivalent ligands with an oxygen-containing linker folded back upon themselves both in solution and the solid state. Dimers which are folded do not bind to Bz receptors. PMID:18790643

On the folding phenomenon of comet tail rays

NASA Astrophysics Data System (ADS)

Ershkovich, A. I.

1982-01-01

It is shown that the folding phenomenon of the comet tail rays is compatible with the Ferraro isorotation law if the comet tail magnetic field has no azimuthal component, that is, Bphi (the polar angle) equals zero. Considering electric drift due to convectional electric fields, a formula is obtained for the angular rate of a ray closure which reduces to that of Ness and Donn (1966) if the velocity profile across the tail is linear. The magnetic field B of approximately 20-40 gammas in the coma and less than about 10 gammas in the distant tail is estimated under typical solar wind conditions at 1 AU.

Equilibrium denaturation and preferential interactions of an RNA tetraloop with urea

DOE PAGES

Miner, Jacob Carlson; García, Angel Enrique

2017-02-09

Urea is an important organic cosolute with implications in maintaining osmotic stress in cells and differentially stabilizing ensembles of folded biomolecules. We report an equilibrium study of urea-induced denaturation of a hyperstable RNA tetraloop through unbiased replica exchange molecular dynamics. We find that, in addition to destabilizing the folded state, urea smooths the RNA free energy landscape by destabilizing specific configurations, and forming favorable interactions with RNA nucleobases. A linear concentration-dependence of the free energy (m-value) is observed, in agreement with the results of other RNA hairpins and proteins. Additionally, analysis of the hydrogen-bonding and stacking interactions within RNA primarilymore » show temperature-dependence, while interactions between RNA and urea primarily show concentration-dependence. Lastly, our findings provide valuable insight into the effects of urea on RNA folding and describe the thermodynamics of a basic RNA hairpin as a function of solution chemistry.« less

Single-molecule Protein Unfolding in Solid State Nanopores

PubMed Central

Talaga, David S.; Li, Jiali

2009-01-01

We use single silicon nitride nanopores to study folded, partially folded and unfolded single proteins by measuring their excluded volumes. The DNA-calibrated translocation signals of β-lactoglobulin and histidine-containing phosphocarrier protein match quantitatively with that predicted by a simple sum of the partial volumes of the amino acids in the polypeptide segment inside the pore when translocation stalls due to the primary charge sequence. Our analysis suggests that the majority of the protein molecules were linear or looped during translocation and that the electrical forces present under physiologically relevant potentials can unfold proteins. Our results show that the nanopore translocation signals are sensitive enough to distinguish the folding state of a protein and distinguish between proteins based on the excluded volume of a local segment of the polypeptide chain that transiently stalls in the nanopore due to the primary sequence of charges. PMID:19530678

Off-axis phonon and photon propagation in porous silicon superlattices studied by Brillouin spectroscopy and optical reflectance

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

Parsons, L. C., E-mail: lcparsons@mun.ca; Andrews, G. T., E-mail: tandrews@mun.ca

2014-07-21

Brillouin light scattering experiments and optical reflectance measurements were performed on a pair of porous silicon-based optical Bragg mirrors which had constituent layer porosity ratios close to unity. For off-axis propagation, the phononic and photonic band structures of the samples were modeled as a series of intersecting linear dispersion curves. Zone-folding was observed for the longitudinal bulk acoustic phonon and the frequency of the probed zone-folded longitudinal phonon was shown to be dependent on the propagation direction as well as the folding order of the mode branch. There was no conclusive evidence of coupling between the transverse and the foldedmore » longitudinal modes. Two additional observed Brillouin peaks were attributed to the Rayleigh surface mode and a possible pseudo-surface mode. Both of these modes were dispersive, with the velocity increasing as the wavevector decreased.« less

Equilibrium Denaturation and Preferential Interactions of an RNA Tetraloop with Urea.

PubMed

Miner, Jacob C; García, Angel E

2017-04-20

Urea is an important organic cosolute with implications in maintaining osmotic stress in cells and differentially stabilizing ensembles of folded biomolecules. We report an equilibrium study of urea-induced denaturation of a hyperstable RNA tetraloop through unbiased replica exchange molecular dynamics. We find that, in addition to destabilizing the folded state, urea smooths the RNA free energy landscape by destabilizing specific configurations, and forming favorable interactions with RNA nucleobases. A linear concentration-dependence of the free energy (m-value) is observed, in agreement with the results of other RNA hairpins and proteins. Additionally, analysis of the hydrogen-bonding and stacking interactions within RNA primarily show temperature-dependence, while interactions between RNA and urea primarily show concentration-dependence. Our findings provide valuable insight into the effects of urea on RNA folding and describe the thermodynamics of a basic RNA hairpin as a function of solution chemistry.

Equilibrium denaturation and preferential interactions of an RNA tetraloop with urea

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

Miner, Jacob Carlson; García, Angel Enrique

Urea is an important organic cosolute with implications in maintaining osmotic stress in cells and differentially stabilizing ensembles of folded biomolecules. We report an equilibrium study of urea-induced denaturation of a hyperstable RNA tetraloop through unbiased replica exchange molecular dynamics. We find that, in addition to destabilizing the folded state, urea smooths the RNA free energy landscape by destabilizing specific configurations, and forming favorable interactions with RNA nucleobases. A linear concentration-dependence of the free energy (m-value) is observed, in agreement with the results of other RNA hairpins and proteins. Additionally, analysis of the hydrogen-bonding and stacking interactions within RNA primarilymore » show temperature-dependence, while interactions between RNA and urea primarily show concentration-dependence. Lastly, our findings provide valuable insight into the effects of urea on RNA folding and describe the thermodynamics of a basic RNA hairpin as a function of solution chemistry.« less

Ultrasound beam characteristics of a symmetric nodal origami based array

NASA Astrophysics Data System (ADS)

Bilgunde, Prathamesh N.; Bond, Leonard J.

2018-04-01

Origami-the ancient art of paper folding-is being explored in acoustics for effective focusing of sound. In this short communication, we present a numerical investigation of beam characteristics for an origami based ultrasound array. A spatial re-configuration of array elements is performed based upon the symmetric nodal origami. The effect of fold angle on the ultrasound beam is evaluated using frequency domain and transient finite element analysis. It was found that increase in the fold angle reduces near field length by 58% and also doubles the beam intensity as compared to the linear array. Transient analysis also indicated 80% reduction in the -6dB beam width, which can improve the lateral resolution of phased array. Such a spatially re-configurable array could potentially be used in the future to reduce the cost of electronics in the phased array instrumentation.

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

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

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

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

An immersed-boundary method for flow–structure interaction in biological systems with application to phonation

PubMed Central

Luo, Haoxiang; Mittal, Rajat; Zheng, Xudong; Bielamowicz, Steven A.; Walsh, Raymond J.; Hahn, James K.

2008-01-01

A new numerical approach for modeling a class of flow–structure interaction problems typically encountered in biological systems is presented. In this approach, a previously developed, sharp-interface, immersed-boundary method for incompressible flows is used to model the fluid flow and a new, sharp-interface Cartesian grid, immersed boundary method is devised to solve the equations of linear viscoelasticity that governs the solid. The two solvers are coupled to model flow–structure interaction. This coupled solver has the advantage of simple grid generation and efficient computation on simple, single-block structured grids. The accuracy of the solid-mechanics solver is examined by applying it to a canonical problem. The solution methodology is then applied to the problem of laryngeal aerodynamics and vocal fold vibration during human phonation. This includes a three-dimensional eigen analysis for a multi-layered vocal fold prototype as well as two-dimensional, flow-induced vocal fold vibration in a modeled larynx. Several salient features of the aerodynamics as well as vocal-fold dynamics are presented. PMID:19936017

Mechanism-based inactivation of CYP2C8 by gemfibrozil occurs rapidly in humans.

PubMed

Honkalammi, J; Niemi, M; Neuvonen, P J; Backman, J T

2011-04-01

To study the time to onset of mechanism-based inactivation of cytochrome P450 (CYP) 2C8 by gemfibrozil in vivo, we conducted a randomized five-phase crossover study in 10 healthy volunteers. In one phase the volunteers ingested 0.25 mg of repaglinide alone (control), and in the other phases they received 600 mg of gemfibrozil 0-6 h prior to the repaglinide dose. When gemfibrozil was taken 0, 1, 3, or 6 h before repaglinide, the geometric mean ratio relative to control (90% confidence interval (CI)) of repaglinide area under the plasma concentration-time curve (AUC(0-∞)) was 5.0-fold (4.3-5.7-fold), 6.3-fold (5.4-7.5-fold), 6.6-fold (5.6-7.7-fold), and 5.4-fold (4.8-6.1-fold), respectively (P < 0.001 vs. control). The geometric mean ratio relative to control (90% CI) of the maximum plasma concentration (C(max)) of the CYP2C8-mediated metabolite M4 was 1.0-fold (0.8-1.3-fold), 0.10-fold (0.06-0.17-fold, P < 0.001), 0.06-fold (0.04-0.10-fold, P < 0.001), and 0.09-fold (0.05-0.14-fold, P < 0.001), respectively. The strong inactivation of CYP2C8, evident as soon as 1 h after gemfibrozil dosing, has implications in clinical practice and in studies with gemfibrozil as a CYP2C8 model inhibitor.

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.

How long does it take to equilibrate the unfolded state of a protein?

PubMed Central

Levy, Ronald M; Dai, Wei; Deng, Nan-Jie; Makarov, Dmitrii E

2013-01-01

How long does it take to equilibrate the unfolded state of a protein? The answer to this question has important implications for our understanding of why many small proteins fold with two state kinetics. When the equilibration within the unfolded state U is much faster than the folding, the folding kinetics will be two state even if there are many folding pathways with different barriers. Yet the mean first passage times (MFPTs) between different regions of the unfolded state can be much longer than the folding time. This seems to imply that the equilibration within U is much slower than the folding. In this communication we resolve this paradox. We present a formula for estimating the time to equilibrate the unfolded state of a protein. We also present a formula for the MFPT to any state within U, which is proportional to the average lifetime of that state divided by the state population. This relation is valid when the equilibration within U is very fast as compared with folding as it often is for small proteins. To illustrate the concepts, we apply the formulas to estimate the time to equilibrate the unfolded state of Trp-cage and MFPTs within the unfolded state based on a Markov State Model using an ultra-long 208 microsecond trajectory of the miniprotein to parameterize the model. The time to equilibrate the unfolded state of Trp-cage is ∼100 ns while the typical MFPTs within U are tens of microseconds or longer. PMID:23963761

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

Determinants of linear growth in Malaysian children with cerebral palsy.

PubMed

Zainah, S H; Ong, L C; Sofiah, A; Poh, B K; Hussain, I H

2001-08-01

To compare the linear growth and nutritional parameters of a group of Malaysian children with cerebral palsy (CP) against a group of controls, and to determine the nutritional, medical and sociodemographic factors associated with poor growth in children with CP. The linear growth of 101 children with CP and of their healthy controls matched for age, sex and ethnicity was measured using upper-arm length (UAL). Nutritional parameters of weight, triceps skin-fold thickness and mid-arm circumference were also measured. Total caloric intake was assessed using a 24-h recall of a 3-day food intake and calculated as a percentage of the Recommended Daily Allowance. Multiple regression analysis was used to determine nutritional, medical and sociodemographic factors associated with poor growth (using z-scores of UAL) in children with CP. Compared with the controls, children with CP had significantly lower mean UAL measurements (difference between means -1.1, 95% confidence interval -1.65 to - 0.59), weight (difference between means -6.0, 95% CI -7.66 to -4.34), mid-arm circumference (difference between means -1.3, 95% CI -2.06 to -0.56) and triceps skin-fold thickness (difference between means -2.5, 95% CI -3.5 to -1.43). Factors associated with low z-scores of UAL were a lower percentage of median weight (P < 0.001), tube feeding (P < 0.001) and increasing age (P < 0.001). A large proportion of Malaysian children with CP have poor nutritional status and linear growth. Nutritional assessment and management at an early age might help this group of children achieve adequate growth.

Vocal Dose Measures: Quantifying Accumulated Vibration Exposure in Vocal Fold Tissues

PubMed Central

Titze, Ingo R.; Švec, Jan G.; Popolo, Peter S.

2011-01-01

To measure the exposure to self-induced tissue vibration in speech, three vocal doses were defined and described: distance dose, which accumulates the distance that tissue particles of the vocal folds travel in an oscillatory trajectory; energy dissipation dose, which accumulates the total amount of heat dissipated over a unit volume of vocal fold tissues; and time dose, which accumulates the total phonation time. These doses were compared to a previously used vocal dose measure, the vocal loading index, which accumulates the number of vibration cycles of the vocal folds. Empirical rules for viscosity and vocal fold deformation were used to calculate all the doses from the fundamental frequency (F0) and sound pressure level (SPL) values of speech. Six participants were asked to read in normal, monotone, and exaggerated speech and the doses associated with these vocalizations were calculated. The results showed that large F0 and SPL variations in speech affected the dose measures, suggesting that accumulation of phonation time alone is insufficient. The vibration exposure of the vocal folds in normal speech was related to the industrial limits for hand-transmitted vibration, in which the safe distance dose was derived to be about 500 m. This limit was found rather low for vocalization; it was related to a comparable time dose of about 17 min of continuous vocalization, or about 35 min of continuous reading with normal breathing and unvoiced segments. The voicing pauses in normal speech and dialogue effectively prolong the safe time dose. The derived safety limits for vocalization will likely require refinement based on a more detailed knowledge of the differences in hand and vocal fold tissue morphology and their response to vibrational stress, and on the effect of recovery of the vocal fold tissue during voicing pauses. PMID:12959470

Vocal dose measures: quantifying accumulated vibration exposure in vocal fold tissues.

PubMed

Titze, Ingo R; Svec, Jan G; Popolo, Peter S

2003-08-01

To measure the exposure to self-induced tissue vibration in speech, three vocal doses were defined and described: distance dose, which accumulates the distance that tissue particles of the vocal folds travel in an oscillatory trajectory; energy dissipation dose, which accumulates the total amount of heat dissipated over a unit volume of vocal fold tissues; and time dose, which accumulates the total phonation time. These doses were compared to a previously used vocal dose measure, the vocal loading index, which accumulates the number of vibration cycles of the vocal folds. Empirical rules for viscosity and vocal fold deformation were used to calculate all the doses from the fundamental frequency (F0) and sound pressure level (SPL) values of speech. Six participants were asked to read in normal, monotone, and exaggerated speech and the doses associated with these vocalizations were calculated. The results showed that large F0 and SPL variations in speech affected the dose measures, suggesting that accumulation of phonation time alone is insufficient. The vibration exposure of the vocal folds in normal speech was related to the industrial limits for hand-transmitted vibration, in which the safe distance dose was derived to be about 500 m. This limit was found rather low for vocalization; it was related to a comparable time dose of about 17 min of continuous vocalization, or about 35 min of continuous reading with normal breathing and unvoiced segments. The voicing pauses in normal speech and dialogue effectively prolong the safe time dose. The derived safety limits for vocalization will likely require refinement based on a more detailed knowledge of the differences in hand and vocal fold tissue morphology and their response to vibrational stress, and on the effect of recovery of the vocal fold tissue during voicing pauses.

Investigation of RNA Hairpin Loop Folding with Time-Resolved Infrared Spectroscopy

NASA Astrophysics Data System (ADS)

Stancik, Aaron Lee

Ribonucleic acids (RNAs) are a group of functional biopolymers central to the molecular underpinnings of life. To complete the many processes they mediate, RNAs must fold into precise three-dimensional structures. Hairpin loops are the most ubiquitous and basic structural elements present in all folded RNAs, and are the foundation upon which all complex tertiary structures are built. A hairpin loop forms when a single stranded RNA molecule folds back on itself creating a helical stem of paired bases capped by a loop. This work investigates the formation of UNCG hairpin loops with the sequence 5'-GC(UNCG)GC-3' (N = A, U, G, or C) using both equilibrium infrared (IR) and time-resolved IR spectroscopy. Equilibrium IR melting data were used to determine thermodynamic parameters. Melting temperatures ranged from 50 to 60°C, and enthalpies of unfolding were on the order of 100 kJ/mol. In the time-resolved work, temperature jumps of up to 20°C at 2.5°C increments were obtained with transient relaxation kinetics spanning nanoseconds to hundreds of microseconds. The relaxation kinetics for all of the oligomers studied were fit to first or second order exponentials. Multiple vibrational transitions were probed on each oligomer for fully folded and partially denatured structures. In the time-resolved limit, in contrast to equilibrium melting, RNA does not fold according to two-state behavior. These results are some of the first to show that RNA hairpins fold according to a rugged energy landscape, which contradicts their relatively simple nature. In addition, this work has proven that time-resolved IR spectroscopy is a powerful and novel tool for investigating the earliest events of RNA folding, the formation of the hairpin loop.

Harnessing Computational Biology for Exact Linear B-Cell Epitope Prediction: A Novel Amino Acid Composition-Based Feature Descriptor.

PubMed

Saravanan, Vijayakumar; Gautham, Namasivayam

2015-10-01

Proteins embody epitopes that serve as their antigenic determinants. Epitopes occupy a central place in integrative biology, not to mention as targets for novel vaccine, pharmaceutical, and systems diagnostics development. The presence of T-cell and B-cell epitopes has been extensively studied due to their potential in synthetic vaccine design. However, reliable prediction of linear B-cell epitope remains a formidable challenge. Earlier studies have reported discrepancy in amino acid composition between the epitopes and non-epitopes. Hence, this study proposed and developed a novel amino acid composition-based feature descriptor, Dipeptide Deviation from Expected Mean (DDE), to distinguish the linear B-cell epitopes from non-epitopes effectively. In this study, for the first time, only exact linear B-cell epitopes and non-epitopes have been utilized for developing the prediction method, unlike the use of epitope-containing regions in earlier reports. To evaluate the performance of the DDE feature vector, models have been developed with two widely used machine-learning techniques Support Vector Machine and AdaBoost-Random Forest. Five-fold cross-validation performance of the proposed method with error-free dataset and dataset from other studies achieved an overall accuracy between nearly 61% and 73%, with balance between sensitivity and specificity metrics. Performance of the DDE feature vector was better (with accuracy difference of about 2% to 12%), in comparison to other amino acid-derived features on different datasets. This study reflects the efficiency of the DDE feature vector in enhancing the linear B-cell epitope prediction performance, compared to other feature representations. The proposed method is made as a stand-alone tool available freely for researchers, particularly for those interested in vaccine design and novel molecular target development for systems therapeutics and diagnostics: https://github.com/brsaran/LBEEP.

Frequency and time properties of decimeter narrowband spikes in solar flares

NASA Astrophysics Data System (ADS)

Wang, Shujuan

2013-07-01

In this paper, we focus to study the frequency and time properties of a group of spikes recorded by the 1.08-2.04 GHz spectrometer of NAOC on 27 October 2003. At the first we calculate the mean and minimum bandwidth of the spikes. We apply two different methods based on the wavelet analysis according to Messmer & Benz (2000). The first method determines the dominant spike bandwidth scale based on their scalegram, and the second method is a feature detection algorithm in the time-frequency plane. Secondly the time profile of each single spike was fitted and analyzed. In particular, we determined the e-folding rise and decay times corresponding to the ascending and decaying parts of the time profile, respectively. Several important correlations were studied and compared with the results in earlier literature, i.e. those between duration and frequency, e-folding rise time and decay time, e-folding decay time and duration, and e-folding decay time and peak flux. Finally some parameters of source region were estimated and the possible decaying mechanism was discussed.

A Flexible Annular-Array Imaging Platform for Micro-Ultrasound

PubMed Central

Qiu, Weibao; Yu, Yanyan; Chabok, Hamid Reza; Liu, Cheng; Tsang, Fu Keung; Zhou, Qifa; Shung, K. Kirk; Zheng, Hairong; Sun, Lei

2013-01-01

Micro-ultrasound is an invaluable imaging tool for many clinical and preclinical applications requiring high resolution (approximately several tens of micrometers). Imaging systems for micro-ultrasound, including single-element imaging systems and linear-array imaging systems, have been developed extensively in recent years. Single-element systems are cheaper, but linear-array systems give much better image quality at a higher expense. Annular-array-based systems provide a third alternative, striking a balance between image quality and expense. This paper presents the development of a novel programmable and real-time annular-array imaging platform for micro-ultrasound. It supports multi-channel dynamic beamforming techniques for large-depth-of-field imaging. The major image processing algorithms were achieved by a novel field-programmable gate array technology for high speed and flexibility. Real-time imaging was achieved by fast processing algorithms and high-speed data transfer interface. The platform utilizes a printed circuit board scheme incorporating state-of-the-art electronics for compactness and cost effectiveness. Extensive tests including hardware, algorithms, wire phantom, and tissue mimicking phantom measurements were conducted to demonstrate good performance of the platform. The calculated contrast-to-noise ratio (CNR) of the tissue phantom measurements were higher than 1.2 in the range of 3.8 to 8.7 mm imaging depth. The platform supported more than 25 images per second for real-time image acquisition. The depth-of-field had about 2.5-fold improvement compared to single-element transducer imaging. PMID:23287923

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.

How do horizontal, frictional discontinuities affect reverse fault-propagation folding?

NASA Astrophysics Data System (ADS)

Bonanno, Emanuele; Bonini, Lorenzo; Basili, Roberto; Toscani, Giovanni; Seno, Silvio

2017-09-01

The development of new reverse faults and related folds is strongly controlled by the mechanical characteristics of the host rocks. In this study we analyze the impact of a specific kind of anisotropy, i.e. thin mechanical and frictional discontinuities, in affecting the development of reverse faults and of the associated folds using physical scaled models. We perform analog modeling introducing one or two initially horizontal, thin discontinuities above an initially blind fault dipping at 30° in one case, and 45° in another, and then compare the results with those obtained from a fully isotropic model. The experimental results show that the occurrence of thin discontinuities affects both the development and the propagation of new faults and the shape of the associated folds. New faults 1) accelerate or decelerate their propagation depending on the location of the tips with respect to the discontinuities, 2) cross the discontinuities at a characteristic angle (∼90°), and 3) produce folds with different shapes, resulting not only from the dip of the new faults but also from their non-linear propagation history. Our results may have direct impact on future kinematic models, especially those aimed to reconstruct the tectonic history of faults that developed in layered rocks or in regions affected by pre-existing faults.

Shear zones of the Verkhoyansk fold-and-thrust belt, Northeast Russia

NASA Astrophysics Data System (ADS)

Fridovsky, Valery; Polufuntikova, Lena

2017-04-01

The Verkhoyansk fold-and-thrust belt is situated on the submerged eastern margin of the North Asian craton, and is largely composed of the Ediacaran - Middle Paleozoic carbonate and the Upper Paleozoic-Mesozoic terrigenous rocks. The Upper Carboniferous - Jurassic sediments constitute the Verkhoyansk terrigenous complex containing economically viable orogenic gold deposits. The structure of the belt is mainly controlled by thrusts and associated diagonal strike slips. Linear concentric folds are common all over the area of the belt. Shear zones with associated similar folds are confined to long narrow areas. Shear zones were formed during the early stages of the Oxfordian-Kimmeridgian collisional and accretionary events prior to the emplacement of large orogenic granitoid plutons. The main ore-controlling structures are shear zones associated with slaty cleavage, shear folds, mullion- and boudinage-structures, and transposition features. The shear zones are listric-type, and represent branches of a detachment structure, which is assumed to be present at the base of the Verkhoyansk fold-and-thrust belt. A vertical zonation of shear zones is correlated with the distance to the detachment. Changes in the dip angle of the shear zones (as indicated mainly by cleavage), structural paragenesis, the degree of microdeformation of the host rocks, and the type of ore-controlling structures can be clearly observed in the direction away from the detachment. Structural zoning is evidenced, among other things, by changing morphologic types of microstructures and by strain-indicators of the degree of rock metamorphism. Four morphologic types of microstructures are identified. The first platy-shear type is characterized by aggregate cleavage and the coefficient of deformation (Cd) of single grains from 1.0 to 2.0. Irregular angular fragments of variously oriented grains can be observed in thin sections. The second shear-cataclastic morphologic type (Cd from 2.0 to 3.0) exhibits combined aggregate and intergranular cleavage. The third cataclastic-segregation morphologic type (Cd from 3.0 to 4.5) is distinguished by a wide distribution of lentelliptical grains of rock-forming minerals in a finely-crystalline matrix and by intergranular cleavage. The rocks of the fourth segregation-striate morphologic type (Cd >5.0) contain lenticular segregations of quartz and feldspar in an intensely linearized mylonite groundmass.

Folding Inquiry into Cookbook Lab Activities

ERIC Educational Resources Information Center

Gooding, Julia; Metz, Bill

2012-01-01

Cookbook labs have been a part of science programs for years, even though they serve little purpose other than to verify phenomena that have been previously presented by means other than through investigations. Cookbook science activities follow a linear path to a known outcome, telling students what procedures to follow, which materials to use,…

Self-Assembly of Emulsion Droplets into Polymer Chains

NASA Astrophysics Data System (ADS)

Bargteil, Dylan; McMullen, Angus; Brujic, Jasna

We experimentally investigate `beads-on-a-string' models of polymers using the spontaneous assembly of emulsion droplets into linear chains. Droplets functionalized with surface-mobile DNA allow for programmable 'monomers' through which we can influence the three-dimensional structure of the assembled 'polymer'. Such model polymers can be used to study conformational changes of polypeptides and the principles governing protein folding. In our system, we find that droplets bind via complementary DNA strands that are recruited into adhesion patches. Recruitment is driven by the DNA hybridization energy, and is limited by the energy cost of surface deformation and the entropy loss of the mobile linkers, yielding adhesion patches of a characteristic size with a given number of linkers. By tuning the initial surface coverage of linkers, we control valency between the droplets to create linear or branched polymer chains. We additionally control the flexibility of the model polymers by varying the salt concentration and study their dynamics between extended and collapsed states. This system opens the possibility of programming stable three-dimensional structures, such as those found within folded proteins.

State preparation and detector effects in quantum measurements of rotation with circular polarization-entangled photons and photon counting

NASA Astrophysics Data System (ADS)

Cen, Longzhu; Zhang, Zijing; Zhang, Jiandong; Li, Shuo; Sun, Yifei; Yan, Linyu; Zhao, Yuan; Wang, Feng

2017-11-01

Circular polarization-entangled photons can be used to obtain an enhancement of the precision in a rotation measurement. In this paper, the method of entanglement transformation is used to produce NOON states in circular polarization from a readily generated linear polarization-entangled photon source. Detection of N -fold coincidences serves as the postselection and N -fold superoscillating fringes are obtained simultaneously. A parity strategy and conditional probabilistic statistics contribute to a better fringe, saturating the angle sensitivity to the Heisenberg limit. The impact of imperfect state preparation and detection is discussed both separately and jointly. For the separated case, the influence of each system imperfection is pronounced. For the joint case, the feasibility region for surpassing the standard quantum limit is given. Our work pushes the state preparation of circular polarization-entangled photons to the same level as that in the case of linear polarization. It is also confirmed that entanglement can be transformed into different frames for specific applications, serving as a useful scheme for using entangled sources.

Intranasal Pharmacokinetic Data for Triptans Such as Sumatriptan and Zolmitriptan Can Render Area Under the Curve (AUC) Predictions for the Oral Route: Strategy Development and Application.

PubMed

Srinivas, Nuggehally R; Syed, Muzeeb

2016-01-01

Limited pharmacokinetic sampling strategy may be useful for predicting the area under the curve (AUC) for triptans and may have clinical utility as a prospective tool for prediction. Using appropriate intranasal pharmacokinetic data, a Cmax vs. AUC relationship was established by linear regression models for sumatriptan and zolmitriptan. The predictions of the AUC values were performed using published mean/median Cmax data and appropriate regression lines. The quotient of observed and predicted values rendered fold-difference calculation. The mean absolute error (MAE), mean positive error (MPE), mean negative error (MNE), root mean square error (RMSE), correlation coefficient (r), and the goodness of the AUC fold prediction were used to evaluate the two triptans. Also, data from the mean concentration profiles at time points of 1 hour (sumatriptan) and 3 hours (zolmitriptan) were used for the AUC prediction. The Cmax vs. AUC models displayed excellent correlation for both sumatriptan (r = .9997; P < .001) and zolmitriptan (r = .9999; P < .001). Irrespective of the two triptans, the majority of the predicted AUCs (83%-85%) were within 0.76-1.25-fold difference using the regression model. The prediction of AUC values for sumatriptan or zolmitriptan using the concentration data that reflected the Tmax occurrence were in the proximity of the reported values. In summary, the Cmax vs. AUC models exhibited strong correlations for sumatriptan and zolmitriptan. The usefulness of the prediction of the AUC values was established by a rigorous statistical approach.

Hemorrhagic and ischemic strokes compared: stroke severity, mortality, and risk factors.

PubMed

Andersen, Klaus Kaae; Olsen, Tom Skyhøj; Dehlendorff, Christian; Kammersgaard, Lars Peter

2009-06-01

Stroke patients with hemorrhagic (HS) and ischemic strokes were compared with regard to stroke severity, mortality, and cardiovascular risk factors. A registry started in 2001, with the aim of registering all hospitalized stroke patients in Denmark, now holds information for 39,484 patients. The patients underwent an evaluation including stroke severity (Scandinavian Stroke Scale), CT, and cardiovascular risk factors. They were followed-up from admission until death or censoring in 2007. Independent predictors of death were identified by means of a survival model based on 25,123 individuals with a complete data set. Of the patients 3993 (10.1%) had HS. Stroke severity was almost linearly related to the probability of having HS (2% in patients with the mildest stroke and 30% in those with the most severe strokes). Factors favoring ischemic strokes vs HS were diabetes, atrial fibrillation, previous myocardial infarction, previous stroke, and intermittent arterial claudication. Smoking and alcohol consumption favored HS, whereas age, sex, and hypertension did not herald stroke type. Compared with ischemic strokes, HS was associated with an overall higher mortality risk (HR, 1.564; 95% CI, 1.441-1.696). The increased risk was, however, time-dependent; initially, risk was 4-fold, after 1 week it was 2.5-fold, and after 3 weeks it was 1.5-fold. After 3 months stroke type did not correlate to mortality. Strokes are generally more severe in patients with HS. Within the first 3 months after stroke, HS is associated with a considerable increase of mortality, which is specifically associated with the hemorrhagic nature of the lesion.

Physical constraints in the condensation of eukaryotic chromosomes. Local concentration of DNA versus linear packing ratio in higher order chromatin structures.

PubMed

Daban, J R

2000-04-11

The local concentration of DNA in metaphase chromosomes of different organisms has been determined in several laboratories. The average of these measurements is 0.17 g/mL. In the first level of chromosome condensation, DNA is wrapped around histones forming nucleosomes. This organization limits the DNA concentration in nucleosomes to 0. 3-0.4 g/mL. Furthermore, in the structural models suggested in different laboratories for the 30-40 nm chromatin fiber, the estimated DNA concentration is significantly reduced; it ranges from 0.04 to 0.27 g/mL. The DNA concentration is further reduced when the fiber is folded into the successive higher order structures suggested in different models for metaphase chromosomes; the estimated minimum decrease of DNA concentration represents an additional 40%. These observations suggest that most of the models proposed for the 30-40 nm chromatin fiber are not dense enough for the construction of metaphase chromosomes. In contrast, it is well-known that the linear packing ratio increases dramatically in each level of DNA folding in chromosomes. Thus, the consideration of the linear packing ratio is not enough for the study of chromatin condensation; the constraint resulting from the actual DNA concentration in metaphase chromosomes must be considered for the construction of models for condensed chromatin.

Clinical Pharmacokinetics of Sacubitril/Valsartan (LCZ696): A Novel Angiotensin Receptor-Neprilysin Inhibitor.

PubMed

Ayalasomayajula, Surya; Langenickel, Thomas; Pal, Parasar; Boggarapu, Sreedevi; Sunkara, Gangadhar

2017-12-01

Sacubitril/valsartan (LCZ696) is indicated for the treatment of heart failure with reduced ejection fraction. Absorption of sacubitril/valsartan and conversion of sacubitril (prodrug) to sacubitrilat (neprilysin inhibitor) was rapid with maximum plasma concentrations of sacubitril, sacubitrilat, and valsartan (angiotensin receptor blocker) reaching within 0.5, 1.5-2.0, and 2.0-3.0 h, respectively. With a two-fold increase in dose, an increase in the area under the plasma concentration-time curve was proportional for sacubitril, ~1.9-fold for sacubitrilat, and ~1.7-fold for valsartan in healthy subjects. Following multiple twice-daily administration, steady-state maximum plasma concentration was reached within 3 days, showing no accumulation for sacubitril and valsartan, while ~1.6-fold accumulation for sacubitrilat. Sacubitril is eliminated predominantly as sacubitrilat through the kidney; valsartan is eliminated mainly by biliary route. Drug-drug interactions of sacubitril/valsartan were evaluated with medications commonly used in patients with heart failure including furosemide, warfarin, digoxin, carvedilol, levonorgestrel/ethinyl estradiol combination, amlodipine, omeprazole, hydrochlorothiazide, intravenous nitrates, metformin, statins, and sildenafil. Co-administration with sacubitril/valsartan increased the maximum plasma concentration (~2.0-fold) and area under the plasma concentration-time curve (1.3-fold) of atorvastatin; however, it did not affect the pharmacokinetics of simvastatin. Age, sex, or ethnicity did not affect the pharmacokinetics of sacubitril/valsartan. In patients with heart failure vs. healthy subjects, area under the plasma concentration-time curves of sacubitril, sacubitrilat, and valsartan were higher by approximately 1.6-, 2.1-, and 2.3-fold, respectively. Renal impairment had no significant impact on sacubitril and valsartan area under the plasma concentration-time curves, while the area under the plasma concentration-time curve of sacubitrilat correlated with degree of renal function (1.3-, 2.3-, 2.9-, and 3.3-fold with mild, moderate, and severe renal impairment, and end-stage renal disease, respectively). Moderate hepatic impairment increased the area under the plasma concentration-time curves of valsartan and sacubitrilat ~2.1-fold.

[Difference of three standard curves of real-time reverse-transcriptase PCR in viable Vibrio parahaemolyticus quantification].

PubMed

Jin, Mengtong; Sun, Wenshuo; Li, Qin; Sun, Xiaohong; Pan, Yingjie; Zhao, Yong

2014-04-04

We evaluated the difference of three standard curves in quantifying viable Vibrio parahaemolyticus in samples by real-time reverse-transcriptase PCR (Real-time RT-PCR). The standard curve A was established by 10-fold diluted cDNA. The cDNA was reverse transcripted after RNA synthesized in vitro. The standard curve B and C were established by 10-fold diluted cDNA. The cDNA was synthesized after RNA isolated from Vibrio parahaemolyticus in pure cultures (10(8) CFU/mL) and shrimp samples (10(6) CFU/g) (Standard curve A and C were proposed for the first time). Three standard curves were performed to quantitatively detect V. parahaemolyticus in six samples, respectively (Two pure cultured V. parahaemolyticus samples, two artificially contaminated cooked Litopenaeus vannamei samples and two artificially contaminated Litopenaeus vannamei samples). Then we evaluated the quantitative results of standard curve and the plate counting results and then analysed the differences. The three standard curves all show a strong linear relationship between the fractional cycle number and V. parahaemolyticus concentration (R2 > 0.99); The quantitative results of Real-time PCR were significantly (p < 0.05) lower than the results of plate counting. The relative errors compared with the results of plate counting ranked standard curve A (30.0%) > standard curve C (18.8%) > standard curve B (6.9%); The average differences between standard curve A and standard curve B and C were - 2.25 Lg CFU/mL and - 0.75 Lg CFU/mL, respectively, and the mean relative errors were 48.2% and 15.9%, respectively; The average difference between standard curve B and C was among (1.47 -1.53) Lg CFU/mL and the average relative errors were among 19.0% - 23.8%. Standard curve B could be applied to Real-time RT-PCR when quantify the number of viable microorganisms in samples.

Sensitivity analysis of linear CROW gyroscopes and comparison to a single-resonator gyroscope

NASA Astrophysics Data System (ADS)

Zamani-Aghaie, Kiarash; Digonnet, Michel J. F.

2013-03-01

This study presents numerical simulations of the maximum sensitivity to absolute rotation of a number of coupled resonator optical waveguide (CROW) gyroscopes consisting of a linear array of coupled ring resonators. It examines in particular the impact on the maximum sensitivity of the number of rings, of the relative spatial orientation of the rings (folded and unfolded), of various sequences of coupling ratios between the rings and various sequences of ring dimensions, and of the number of input/output waveguides (one or two) used to inject and collect the light. In all configurations the sensitivity is maximized by proper selection of the coupling ratio(s) and phase bias, and compared to the maximum sensitivity of a resonant waveguide optical gyroscope (RWOG) utilizing a single ring-resonator waveguide with the same radius and loss as each ring in the CROW. Simulations show that although some configurations are more sensitive than others, in spite of numerous claims to the contrary made in the literature, in all configurations the maximum sensitivity is independent of the number of rings, and does not exceed the maximum sensitivity of an RWOG. There are no sensitivity benefits to utilizing any of these linear CROWs for absolute rotation sensing. For equal total footprint, an RWOG is √N times more sensitive, and it is easier to fabricate and stabilize.

Development of Bonded Joint Technology for a Rigidizable-Inflatable Deployable Truss

NASA Technical Reports Server (NTRS)

Smeltzer, Stanley S., III

2006-01-01

Microwave and Synthetic Aperture Radar antenna systems have been developed as instrument systems using truss structures as their primary support and deployment mechanism for over a decade. NASA Langley Research Center has been investigating fabrication, modular assembly, and deployment methods of lightweight rigidizable/inflatable linear truss structures during that time for large spacecraft systems. The primary goal of the research at Langley Research Center is to advance these existing state-of-the-art joining and deployment concepts to achieve prototype system performance in a relevant space environment. During 2005, the development, fabrication, and testing of a 6.7 meter multi-bay, deployable linear truss was conducted at Langley Research Center to demonstrate functional and precision metrics of a rigidizable/inflatable truss structure. The present paper is intended to summarize aspects of bonded joint technology developed for the 6.7 meter deployable linear truss structure while providing a brief overview of the entire truss fabrication, assembly, and deployment methodology. A description of the basic joint design, surface preparation investigations, and experimental joint testing of component joint test articles will be described. Specifically, the performance of two room temperature adhesives were investigated to obtain qualitative data related to tube folding testing and quantitative data related to tensile shear strength testing. It was determined from the testing that a polyurethane-based adhesive best met the rigidizable/inflatable truss project requirements.

Development of Vibrational Culture Model Mimicking Vocal Fold Tissues.

PubMed

Kim, Dongjoo; Lim, Jae-Yol; Kwon, Soonjo

2016-10-01

The vocal folds (VFs) are connective tissues with complex matrix structures that provide the required mechanical properties for voice generation. VF injury leads to changes in tissue structure and properties, resulting in reduced voice quality. However, injury-induced biochemical changes and repair in scarred VF tissues have not been well characterized to date. To treat scarred VFs, it is essential to understand how physiological characteristics of VFs tissue change in response to external perturbation. In this study, we designed a simple vibrational culture model to mimic vibratory microenvironments observed in vivo. This model consists of a flexible culture plate, three linear actuators, a stereo splitter, and a function generator. Human vocal fold fibroblast (hVFF) monolayers were established on the flexible membrane, to which normal phonatory vibrations were delivered from linear actuators and a function generator. The hVFF monolayers were exposed to the vibrational stresses at a frequency of 205 Hz for 2, 6, and 10 h with maximum displacement of 47.1 μm, followed by a 6 h rest. We then observed the changes in cell morphology, cell viability, and gene expression related to extracellular matrix components. In our dynamic culture device mimicking normal phonatory frequencies, cell proliferation increased and expression of hyaluronic acid synthase 2 was downregulated in response to vibrational stresses. The results presented herein will be useful for evaluating cellular responses following VF injuries in the presence or absence of vibrational stresses.

Removal of polycyclic aromatic hydrocarbons from aqueous solution by raw and modified plant residue materials as biosorbents.

PubMed

Xi, Zemin; Chen, Baoliang

2014-04-01

Removal of polycyclic aromatic hydrocarbons (PAHs), e.g., naphthalene, acenaphthene, phenanthrene and pyrene, from aqueous solution by raw and modified plant residues was investigated to develop low cost biosorbents for organic pollutant abatement. Bamboo wood, pine wood, pine needles and pine bark were selected as plant residues, and acid hydrolysis was used as an easily modification method. The raw and modified biosorbents were characterized by elemental analysis, Fourier transform infrared spectroscopy and scanning electron microscopy. The sorption isotherms of PAHs to raw biosorbents were apparently linear, and were dominated by a partitioning process. In comparison, the isotherms of the hydrolyzed biosorbents displayed nonlinearity, which was controlled by partitioning and the specific interaction mechanism. The sorption kinetic curves of PAHs to the raw and modified plant residues fit well with the pseudo second-order kinetics model. The sorption rates were faster for the raw biosorbents than the corresponding hydrolyzed biosorbents, which was attributed to the latter having more condensed domains (i.e., exposed aromatic core). By the consumption of the amorphous cellulose component under acid hydrolysis, the sorption capability of the hydrolyzed biosorbents was notably enhanced, i.e., 6-18 fold for phenanthrene, 6-8 fold for naphthalene and pyrene and 5-8 fold for acenaphthene. The sorption coefficients (Kd) were negatively correlated with the polarity index [(O+N)/C], and positively correlated with the aromaticity of the biosorbents. For a given biosorbent, a positive linear correlation between logKoc and logKow for different PAHs was observed. Interestingly, the linear plots of logKoc-logKow were parallel for different biosorbents. These observations suggest that the raw and modified plant residues have great potential as biosorbents to remove PAHs from wastewater. Copyright © 2014 The Research Centre for Eco-Environmental Sciences, Chinese Academy of Sciences. Published by Elsevier B.V. All rights reserved.

Impact of ion binding on poly-L-lysine (un)folding energy landscape and kinetics.

PubMed

Xiong, Kan; Asher, Sanford A

2012-06-21

We utilize T-jump UV resonance Raman spectroscopy (UVRR) to study the impact of ion binding on the equilibrium energy landscape and on (un)folding kinetics of poly-L-lysine (PLL). We observe that the relaxation rates of the folded conformations (including π-helix (bulge), pure α-helix, and turns) of PLL are slower than those of short alanine-based peptides. The PLL pure α-helix folding time is similar to that of short alanine-based peptides. We for the first time have directly observed that turn conformations are α-helix and π-helix (bulge) unfolding intermediates. ClO(4)(-) binding to the Lys side chain -NH(3)(+) groups and the peptide backbone slows the α-helix unfolding rate compared to that in pure water, but little impacts the folding rate, resulting in an increased α-helix stability. ClO(4)(-) binding significantly increases the PLL unfolding activation barrier but little impacts the folding barrier. Thus, the PLL folding coordinate(s) differs from the unfolding coordinate(s). The-π helix (bulge) unfolding and folding coordinates do not directly go through the α-helix energy well. Our results clearly demonstrate that PLL (un)folding is not a two-state process.

Analysis of Factors Affecting Women of Childbearing Age to Screen Using Visual Inspection with Acetic Acid.

PubMed

Sidabutar, Sondang; Martini, Santi; Wahyuni, Chatarina Umbul

2017-02-01

The purpose of this study was to evaluate patient factors such as knowledge, attitude, motivation, perception, socio-economic status and travel time to health facilities and assess how these factors affected patients' decision to pursue cervical cancer screening with visual inspection with acetic acid (VIA). A total of 80 women of childbearing age who visited Kenjeran and Balongsari Public Health Centers for health assessments were involved in this study. Patients who agreed to participate in the study underwent a verbal questionnaire to evaluate various factors. Bivariate analysis concluded that knowledge, attitude, motivation, perception, socioeconomic status, and travel time to health facilities were significantly different between women who received VIA screening and women who did not receive VIA screening ( p < 0.05). The factors of knowledge, attitudes, motivation, perception, socio-economic status, and the travel time to health facilities accounted for 2.920-fold, 2.043-fold, 3.704-fold, 2.965-fold, 3.198-fold and 2.386-fold possibility, respectively, of patients to pursue cervical cancer screening with VIA. Multivariate analysis showed that perception, socio-economic status, and travel time to health facilities were the most important factors influencing whether or not women pursued VIA screening. Knowledge, attitude, motivation, perception, socio-economic status, and travel time to health facilities appears to affect women's' decision to pursue cervical cancer screening with VIA, with the largest intake being the motivational factor.

Experiment to evaluate feasibility of utilizing Skylab-EREP remote sensing data for tectonic analysis of the Bighorn Mountains region, Wyoming-Montana

NASA Technical Reports Server (NTRS)

Hoppin, R. A. (Principal Investigator)

1974-01-01

The author has identified the following significant results. Analysis of SL-3, S-190A, and S-190B color frames indicates two sets of linears obliquely cutting across the east-west trending Owl Creek-Bridger uplifts. A northwest set of faults and folds has been mapped previously but the imagery indicates some changes and addition of detail can be made. A less pronounced east-northeast set of linear alignments (drainage segments, lithologic contacts, possible faults) extends into the southeast part of the Big Horn Basin.

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.

My 65 years in protein chemistry.

PubMed

Scheraga, Harold A

2015-05-01

This is a tour of a physical chemist through 65 years of protein chemistry from the time when emphasis was placed on the determination of the size and shape of the protein molecule as a colloidal particle, with an early breakthrough by James Sumner, followed by Linus Pauling and Fred Sanger, that a protein was a real molecule, albeit a macromolecule. It deals with the recognition of the nature and importance of hydrogen bonds and hydrophobic interactions in determining the structure, properties, and biological function of proteins until the present acquisition of an understanding of the structure, thermodynamics, and folding pathways from a linear array of amino acids to a biological entity. Along the way, with a combination of experiment and theoretical interpretation, a mechanism was elucidated for the thrombin-induced conversion of fibrinogen to a fibrin blood clot and for the oxidative-folding pathways of ribonuclease A. Before the atomic structure of a protein molecule was determined by x-ray diffraction or nuclear magnetic resonance spectroscopy, experimental studies of the fundamental interactions underlying protein structure led to several distance constraints which motivated the theoretical approach to determine protein structure, and culminated in the Empirical Conformational Energy Program for Peptides (ECEPP), an all-atom force field, with which the structures of fibrous collagen-like proteins and the 46-residue globular staphylococcal protein A were determined. To undertake the study of larger globular proteins, a physics-based coarse-grained UNited-RESidue (UNRES) force field was developed, and applied to the protein-folding problem in terms of structure, thermodynamics, dynamics, and folding pathways. Initially, single-chain and, ultimately, multiple-chain proteins were examined, and the methodology was extended to protein-protein interactions and to nucleic acids and to protein-nucleic acid interactions. The ultimate results led to an understanding of a variety of biological processes underlying natural and disease phenomena.

My 65 years in protein chemistry

PubMed Central

Scheraga, Harold A.

2015-01-01

This is a tour of a physical chemist through 65 years of protein chemistry from the time when emphasis was placed on the determination of the size and shape of the protein molecule as a colloidal particle, with an early breakthrough by James Sumner, followed by Linus Pauling and Fred Sanger, that a protein was a real molecule, albeit a macromolecule. It deals with the recognition of the nature and importance of hydrogen bonds and hydrophobic interactions in determining the structure, properties, and biological function of proteins until the present acquisition of an understanding of the structure, thermodynamics, and folding pathways from a linear array of amino acids to a biological entity. Along the way, with a combination of experiment and theoretical interpretation, a mechanism was elucidated for the thrombin-induced conversion of fibrinogen to a fibrin blood clot and for the oxidative-folding pathways of ribonuclease A. Before the atomic structure of a protein molecule was determined by x-ray diffraction or nuclear magnetic resonance spectroscopy, experimental studies of the fundamental interactions underlying protein structure led to several distance constraints which motivated the theoretical approach to determine protein structure, and culminated in the Empirical Conformational Energy Program for Peptides (ECEPP), an all-atom force field, with which the structures of fibrous collagen-like proteins and the 46-residue globular staphylococcal protein A were determined. To undertake the study of larger globular proteins, a physics-based coarse-grained UNited-RESidue (UNRES) force field was developed, and applied to the protein-folding problem in terms of structure, thermodynamics, dynamics, and folding pathways. Initially, single-chain and, ultimately, multiple-chain proteins were examined, and the methodology was extended to protein–protein interactions and to nucleic acids and to protein–nucleic acid interactions. The ultimate results led to an understanding of a variety of biological processes underlying natural and disease phenomena. PMID:25850343

Application of methyl silane coated iron oxide magnetic nanoparticles for solid-phase extraction and determination of fat-soluble vitamins by high performance liquid chromatography.

PubMed

Momenbeik, Fariborz; Yazdani, Elham

2015-01-01

Methyl silane coated Fe3O4 magnetic nanoparticles were used for simultaneous extraction of the fat-soluble vitamins (FSVs). The amounts of extracted vitamins were determined by HPLC. The synthesized Fe3O4 nanoparticles were coated with silica and then modified with trimethoxymethylsilane (TMMS). The prepared particles were characterized by different methods. The best amounts of silica and TMMS in sorbent synthesis were 1.2 and 0.5 mL, respectively. The optimum pH values for the sample solution and washing buffer were 5 and 3, respectively. Application of 100 mg sorbent, 700 μL tetrahydrofuran, 5-fold dilution of the sample solution, and 1 min for sorption and desorption times were among the best conditions. At the optimum conditions, the calibration plots for each vitamin were obtained with good linearity (R(2) >0.9992) and suitable linear ranges. This method has a low LOD (<76.1 μg/mL), acceptable repeatability (RSD <5.63%) and reproducibility (RSD <4.71%), and good accuracy (recovery >90.3%). Preconcentration of low concentrations of vitamin D3 was performed, and results showed 3.7 times greater sensitivity after preconcentration. Finally, the amounts of the FSVs in pharmaceutical formulations were determined using the proposed method, and results showed good agreement with those reported by manufacturers.

A narrowband filter based on 2D 8-fold photonic quasicrystal

NASA Astrophysics Data System (ADS)

Ren, Jie; Sun, XiaoHong; Wang, Shuai

2018-04-01

In this paper, a novel structure of narrowband filter based on 2D 8-fold photonic quasicrystal (PQC) is proposed and investigated. The structure size is 8 μm × 8 μm, which promises its applications in optical integrated circuits and communication devices. Finite Element Method (FEM) has been employed to investigate the band gap of the filter. The resonance wavelength, transmission coefficient and 3 dB bandwidth are analyzed by varying the parameters of the structure. By optimizing the parameters of the filter, two design formulas of resonance wavelength are obtained. Also, for its better linearity of the resonance, the structure with line-defect has also seen a large uptake in sensor design.

Kinetics studies of rapid strain-promoted [3 + 2]-cycloadditions of nitrones with biaryl-aza-cyclooctynone.

PubMed

McKay, Craig S; Chigrinova, Mariya; Blake, Jessie A; Pezacki, John Paul

2012-04-21

Strain-promoted cycloadditions of cyclic nitrones with biaryl-aza-cyclooctynone (BARAC) proceed with rate constants up to 47.3 M(-1) s(-1), this corresponds to a 47-fold rate enhancement relative to reaction of BARAC with benzyl azide and a 14-fold enhancement over previously reported strain promoted alkyne-nitrone cycloadditions (SPANC). Studies of the SPANC reaction using the linear free energy relationship defined by the Hammett equation demonstrated that the cycloaddition reaction has a rho value of 0.25 ± 0.04, indicating that reaction is not sensitive to substituents and thus should have broad applicability. This journal is © The Royal Society of Chemistry 2012

Maglev crude oil pipeline

NASA Technical Reports Server (NTRS)

Knolle, Ernst G.

1994-01-01

This maglev crude oil pipeline consists of two conduits guiding an endless stream of long containers. One conduit carries loaded containers and the other empty returns. The containers are levitated by permanent magnets in repulsion and propelled by stationary linear induction motors. The containers are linked to each other in a manner that allows them, while in continuous motion, to be folded into side by side position at loading and unloading points. This folding causes a speed reduction in proportion to the ratio of container diameter to container length. While in side by side position, containers are opened at their ends to be filled or emptied. Container size and speed are elected to produce a desired carrying capacity.

Biomechanics of fundamental frequency regulation: Constitutive modeling of the vocal fold lamina propria.

PubMed

Chan, Roger W; Siegmund, Thomas; Zhang, Kai

2009-12-01

Accurate characterization of biomechanical characteristics of the vocal fold is critical for understanding the regulation of vocal fundamental frequency (F(0)), which depends on the active control of the intrinsic laryngeal muscles as well as the passive biomechanical response of the vocal fold lamina propria. Specifically, the tissue stress-strain response and viscoelastic properties under cyclic tensile deformation are relevant, when the vocal folds are subjected to length and tension changes due to posturing. This paper describes a constitutive modeling approach quantifying the relationship between vocal fold stress and strain (or stretch), and establishes predictions of F(0) with the string model of phonation based on the constitutive parameters. Results indicated that transient and time-dependent changes in F(0), including global declinations in declarative sentences, as well as local F(0) overshoots and undershoots, can be partially attributed to the time-dependent viscoplastic response of the vocal fold cover.

Predictability of a Coupled Model of ENSO Using Singular Vector Analysis: Optimal Growth and Forecast Skill.

NASA Astrophysics Data System (ADS)

Xue, Yan

The optimal growth and its relationship with the forecast skill of the Zebiak and Cane model are studied using a simple statistical model best fit to the original nonlinear model and local linear tangent models about idealized climatic states (the mean background and ENSO cycles in a long model run), and the actual forecast states, including two sets of runs using two different initialization procedures. The seasonally varying Markov model best fit to a suite of 3-year forecasts in a reduced EOF space (18 EOFs) fits the original nonlinear model reasonably well and has comparable or better forecast skill. The initial error growth in a linear evolution operator A is governed by the eigenvalues of A^{T}A, and the square roots of eigenvalues and eigenvectors of A^{T}A are named singular values and singular vectors. One dominant growing singular vector is found, and the optimal 6 month growth rate is largest for a (boreal) spring start and smallest for a fall start. Most of the variation in the optimal growth rate of the two forecasts is seasonal, attributable to the seasonal variations in the mean background, except that in the cold events it is substantially suppressed. It is found that the mean background (zero anomaly) is the most unstable state, and the "forecast IC states" are more unstable than the "coupled model states". One dominant growing singular vector is found, characterized by north-south and east -west dipoles, convergent winds on the equator in the eastern Pacific and a deepened thermocline in the whole equatorial belt. This singular vector is insensitive to initial time and optimization time, but its final pattern is a strong function of initial states. The ENSO system is inherently unpredictable for the dominant singular vector can amplify 5-fold to 24-fold in 6 months and evolve into the large scales characteristic of ENSO. However, the inherent ENSO predictability is only a secondary factor, while the mismatches between the model and data is a primary factor controlling the current forecast skill.

Patterned, highly stretchable and conductive nanofibrous PANI/PVDF strain sensors based on electrospinning and in situ polymerization

NASA Astrophysics Data System (ADS)

Yu, Gui-Feng; Yan, Xu; Yu, Miao; Jia, Meng-Yang; Pan, Wei; He, Xiao-Xiao; Han, Wen-Peng; Zhang, Zhi-Ming; Yu, Liang-Min; Long, Yun-Ze

2016-01-01

A facile fabrication strategy via electrospinning and followed by in situ polymerization to fabricate a patterned, highly stretchable, and conductive polyaniline/poly(vinylidene fluoride) (PANI/PVDF) nanofibrous membrane is reported. Owing to the patterned structure, the nanofibrous PANI/PVDF strain sensor can detect a strain up to 110%, for comparison, which is 2.6 times higher than the common nonwoven PANI/PVDF mat and much larger than the previously reported values (usually less than 15%). Meanwhile, the conductivity of the patterned strain sensor shows a linear response to the applied strain in a wide range from 0% to about 85%. Additionally, the patterned PANI/PVDF strain sensor can completely recover to its original electrical and mechanical values within a strain range of more than 22%, and exhibits good durability over 10 000 folding-unfolding tests. Furthermore, the strain sensor also can be used to detect finger motion. The results demonstrate promising application of the patterned nanofibrous membrane in flexible electronic fields.A facile fabrication strategy via electrospinning and followed by in situ polymerization to fabricate a patterned, highly stretchable, and conductive polyaniline/poly(vinylidene fluoride) (PANI/PVDF) nanofibrous membrane is reported. Owing to the patterned structure, the nanofibrous PANI/PVDF strain sensor can detect a strain up to 110%, for comparison, which is 2.6 times higher than the common nonwoven PANI/PVDF mat and much larger than the previously reported values (usually less than 15%). Meanwhile, the conductivity of the patterned strain sensor shows a linear response to the applied strain in a wide range from 0% to about 85%. Additionally, the patterned PANI/PVDF strain sensor can completely recover to its original electrical and mechanical values within a strain range of more than 22%, and exhibits good durability over 10 000 folding-unfolding tests. Furthermore, the strain sensor also can be used to detect finger motion. The results demonstrate promising application of the patterned nanofibrous membrane in flexible electronic fields. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr08618c

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

76 FR 774 - Folding Metal Tables and Chairs From the People's Republic of China: Notice of Extension of Time...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-06

... DEPARTMENT OF COMMERCE International Trade Administration [A-570-868] Folding Metal Tables and... review of the antidumping duty order on folding metal tables and chairs from the People's Republic of China (``PRC''). See Folding Metal Tables and Chairs: Initiation of New Shipper Review, 75 FR 44767...

77 FR 45337 - Folding Gift Boxes From the People's Republic of China: Extension of Time Limits for Preliminary...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-31

... DEPARTMENT OF COMMERCE International Trade Administration [A-570-866] Folding Gift Boxes From the... (``sunset'') review of the antidumping duty (``AD'') order on certain folding gift boxes from the People's...'').\\1\\ The Folding Gift Boxes Fair Trade Coalition,\\2\\ a group of producers of the domestic like product...

Dynamics of Folds in the Plane

ERIC Educational Resources Information Center

Krylov, Nikolai A.; Rogers, Edwin L.

2011-01-01

Take a strip of paper and fold a crease intersecting the long edges, creating two angles. Choose one edge and consider the angle with the crease. Fold the opposite edge along the crease, creating a new crease that bisects the angle. Fold again, this time using the newly created crease and the initial edge, creating a new angle along the chosen…

Whole exome sequence-based association analyses of plasma amyloid-β in African and European Americans; the Atherosclerosis Risk in Communities-Neurocognitive Study.

PubMed

Simino, Jeannette; Wang, Zhiying; Bressler, Jan; Chouraki, Vincent; Yang, Qiong; Younkin, Steven G; Seshadri, Sudha; Fornage, Myriam; Boerwinkle, Eric; Mosley, Thomas H

2017-01-01

We performed single-variant and gene-based association analyses of plasma amyloid-β (aβ) concentrations using whole exome sequence from 1,414 African and European Americans. Our goal was to identify genes that influence plasma aβ42 concentrations and aβ42:aβ40 ratios in late middle age (mean = 59 years), old age (mean = 77 years), or change over time (mean = 18 years). Plasma aβ measures were linearly regressed onto age, gender, APOE ε4 carrier status, and time elapsed between visits (fold-changes only) separately by race. Following inverse normal transformation of the residuals, seqMeta was used to conduct race-specific single-variant and gene-based association tests while adjusting for population structure. Linear regression models were fit on autosomal variants with minor allele frequencies (MAF)≥1%. T5 burden and Sequence Kernel Association (SKAT) gene-based tests assessed functional variants with MAF≤5%. Cross-race fixed effects meta-analyses were Bonferroni-corrected for the number of variants or genes tested. Seven genes were associated with aβ in late middle age or change over time; no associations were identified in old age. Single variants in KLKB1 (rs3733402; p = 4.33x10-10) and F12 (rs1801020; p = 3.89x10-8) were significantly associated with midlife aβ42 levels through cross-race meta-analysis; the KLKB1 variant replicated internally using 1,014 additional participants with exome chip. ITPRIP, PLIN2, and TSPAN18 were associated with the midlife aβ42:aβ40 ratio via the T5 test; TSPAN18 was significant via the cross-race meta-analysis, whereas ITPRIP and PLIN2 were European American-specific. NCOA1 and NT5C3B were associated with the midlife aβ42:aβ40 ratio and the fold-change in aβ42, respectively, via SKAT in African Americans. No associations replicated externally (N = 725). We discovered age-dependent genetic effects, established associations between vascular-related genes (KLKB1, F12, PLIN2) and midlife plasma aβ levels, and identified a plausible Alzheimer's Disease candidate gene (ITPRIP) influencing cell death. Plasma aβ concentrations may have dynamic biological determinants across the lifespan; plasma aβ study designs or analyses must consider age.

Description of the rates, trends and surgical burden associated with revision for prosthetic joint infection following primary and revision knee replacements in England and Wales: an analysis of the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man.

PubMed

Lenguerrand, Erik; Whitehouse, Michael R; Beswick, Andrew D; Toms, Andrew D; Porter, Martyn L; Blom, Ashley W

2017-07-10

To describe the prevalence rates of revision surgery for the treatment of prosthetic joint infection (PJI) for patients undergoing knee replacement, their time trends, the cumulative incidence function of revision for PJI and estimate the burden of PJI at health service level. We analysed revision knee replacements performed due to a diagnosis of PJI and the linked index procedures recorded in the National Joint Registry from 2003 to 2014 for England and Wales. The cohort analysed consisted of 679 010 index primary knee replacements, 33 920 index revision knee replacements and 8247 revision total knee replacements performed due to a diagnosis of PJI. The prevalence rates, their time trends investigated by time from index surgery to revision for PJI, cumulative incidence functions and the burden of PJI (total procedures) were calculated. Overall linear trends were investigated with log-linear regression. The incidence of revision total knee replacement due to PJI at 2 years was 3.2/1000 following primary and 14.4/1000 following revision knee replacement, respectively. The prevalence of revision due to PJI in the 3 months following primary knee replacement has risen by 2.5-fold (95% CI 1.2 to 5.3) from 2005 to 2013 and 7.5-fold (95% CI 1.0 to 56.1) following revision knee replacement. Over 1000 procedures per year are performed as a consequence of knee PJI, an increase of 2.8 from 2005 to 2013. Overall, 75% of revisions were two-stage with an increase in use of single-stage from 7.9% in 2005 to 18.8% in 2014. Although the risk of revision due to PJI following knee replacement is low, it is rising, and coupled with the established and further predicted increased incidence of both primary and revision knee replacements, this represents an increasing and substantial treatment burden for orthopaedic service delivery in England and Wales. This has implications for future service design and the funding of individual and specialist centres. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Description of the rates, trends and surgical burden associated with revision for prosthetic joint infection following primary and revision knee replacements in England and Wales: an analysis of the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man

PubMed Central

Lenguerrand, Erik; Whitehouse, Michael R; Beswick, Andrew D; Toms, Andrew D; Porter, Martyn L; Blom, Ashley W

2017-01-01

Objectives To describe the prevalence rates of revision surgery for the treatment of prosthetic joint infection (PJI) for patients undergoing knee replacement, their time trends, the cumulative incidence function of revision for PJI and estimate the burden of PJI at health service level. Design We analysed revision knee replacements performed due to a diagnosis of PJI and the linked index procedures recorded in the National Joint Registry from 2003 to 2014 for England and Wales. The cohort analysed consisted of 679 010 index primary knee replacements, 33 920 index revision knee replacements and 8247 revision total knee replacements performed due to a diagnosis of PJI. The prevalence rates, their time trends investigated by time from index surgery to revision for PJI, cumulative incidence functions and the burden of PJI (total procedures) were calculated. Overall linear trends were investigated with log-linear regression. Results The incidence of revision total knee replacement due to PJI at 2 years was 3.2/1000 following primary and 14.4/1000 following revision knee replacement, respectively. The prevalence of revision due to PJI in the 3 months following primary knee replacement has risen by 2.5-fold (95% CI 1.2 to 5.3) from 2005 to 2013 and 7.5-fold (95% CI 1.0 to 56.1) following revision knee replacement. Over 1000 procedures per year are performed as a consequence of knee PJI, an increase of 2.8 from 2005 to 2013. Overall, 75% of revisions were two-stage with an increase in use of single-stage from 7.9% in 2005 to 18.8% in 2014. Conclusions Although the risk of revision due to PJI following knee replacement is low, it is rising, and coupled with the established and further predicted increased incidence of both primary and revision knee replacements, this represents an increasing and substantial treatment burden for orthopaedic service delivery in England and Wales. This has implications for future service design and the funding of individual and specialist centres. PMID:28698316

Asthma hospitalization trends in Charleston, South Carolina, 1956 to 1997: twenty-fold increase among black children during a 30-year period.

PubMed

Crater, D D; Heise, S; Perzanowski, M; Herbert, R; Morse, C G; Hulsey, T C; Platts-Mills, T

2001-12-01

The increase in asthma prevalence has been documented worldwide, affecting many races living in many different climates. Multiple studies have demonstrated that the most striking prevalence and morbidity of asthma in the United States has been in black children, but little research has determined the scale of the increase, or specifically when the disease became severe in this group. This study sought to determine exactly when the rise in asthma hospitalizations among black patients began and what the pattern of asthma hospitalizations has been in different races and age groups over a 40-year period in 1 urban area. A retrospective chart review of discharges from the Medical University of South Carolina was conducted from 1956 to 1997. Charts with the primary discharge diagnosis of asthma were examined for discharge date, race, and age group (0- to 4-year-olds, 5- to 18-year-olds, 19- to 50-year-olds, > or =51-year-olds). The diagnostic codes used were based on the International Classification of Diseases (ICD)-6, 1956-1957; ICD-7, 1958-1967; ICD-8, 1968-1978; and ICD-9, 1979-1997. Over the period studied, this hospital was the primary inpatient provider for children in this area, and the only provider for uninsured children. Between 1960 and 1990, the racial makeup of the area remained stable, as did the percentage of blacks living at the poverty level. The raw number of asthma discharges, rate per 10 000 discharges of the same race, and rate per 100 000 population in Charleston County were tabulated for each age group and racial category. Over the time period examined, there has been a progressive increase in asthma hospitalizations in black individuals of all age groups and in whites under 18 years. The most striking increase has been in black children 0 to 18 years old (figure). The increase either as raw values or as a rate per 100 000 began around 1970, and was linear. This increase in black children discharged with asthma as a rate per 100 000 population was 20-fold: the rate increased from 18 in 1970 to 370 in 1997. Asthma discharges as a rate per 10 000 black children discharged increased by 24-fold from 1960 to 1997. Total discharges from the hospital increased from 49 000 to 128 000 per year over this period. Blacks made up only 28% of discharges in 1957, but that proportion increased to 56% in 1960 and remained relatively stable over the following 35 years. The increase seen in white children 0 to 18 years of age as a rate per 100 000 population was 5-fold and began around 1980. Both increases seem to be consistent over the time period studied, and continued to 1997. [figure: see text]. Among a predominantly poor black population living in a southern US city, there has been a steady increase in childhood asthma hospitalizations over the past 30 years. A significant although less dramatic rise has occurred in white children. Over this time period, although there have been many changes in lifestyle that could have contributed to this rise, there have been no major changes in housing conditions for poor patients. In addition, Medicaid coverage for children in South Carolina did not change significantly until 1999. The time course of these increases parallels increases reported in other Western populations, suggesting that there must be 1 or more common factors contributing to the rise. Many explanations have been offered for the changes in incidence and severity of asthma. The scale of the change, time course, and linearity of the increase in this study represent a challenge to many of the hypotheses proposed to explain this epidemic.

Deterministic folding: The role of entropic forces and steric specificities

NASA Astrophysics Data System (ADS)

da Silva, Roosevelt A.; da Silva, M. A. A.; Caliri, A.

2001-03-01

The inverse folding problem of proteinlike macromolecules is studied by using a lattice Monte Carlo (MC) model in which steric specificities (nearest-neighbors constraints) are included and the hydrophobic effect is treated explicitly by considering interactions between the chain and solvent molecules. Chemical attributes and steric peculiarities of the residues are encoded in a 10-letter alphabet and a correspondent "syntax" is provided in order to write suitable sequences for the specified target structures; twenty-four target configurations, chosen in order to cover all possible values of the average contact order χ (0.2381⩽χ⩽0.4947 for this system), were encoded and analyzed. The results, obtained by MC simulations, are strongly influenced by geometrical properties of the native configuration, namely χ and the relative number φ of crankshafts-type structures: For χ<0.35 the folding is deterministic, that is, the syntax is able to encode successful sequences: The system presents larger encodability, minimum sequence-target degeneracies and smaller characteristic folding time τf. For χ⩾0.35 the above results are not reproduced any more: The folding success is severely reduced, showing strong correlation with φ. Additionally, the existence of distinct characteristic folding times suggests that different mechanisms are acting at the same time in the folding process. The results (all obtained from the same single model, under the same "physiological conditions") resemble some general features of the folding problem, supporting the premise that the steric specificities, in association with the entropic forces (hydrophobic effect), are basic ingredients in the protein folding process.

Interactions of agonists with an allosteric antagonist at muscarinic acetylcholine M2 receptors.

PubMed

Lanzafame, A; Christopoulos, A; Mitchelson, F

1996-11-28

The interaction of heptane-1,7-bis(dimethyl-3'-phthalimidopropylammonium bromide) (C7/3'-phth), with several agonists, was investigated at the muscarinic M2 receptor in guinea-pig left atria. C7/3'-phth shifted concentration-response curves for the agonists, carbachol, oxotremorine-M and (+)-cis-dioxolane, to the right in a parallel fashion. Arunlakshana-Schild regressions of the data yielded slopes significantly different to unity, suggesting non-competitive antagonism. Non-linear regression analysis, using an equation based on allosteric modulation, gave quantitative estimates of co-operativity (alpha values) and the dissociation constant of C7/3'-phth (KB). In all cases, the KB estimates for C7/3'-phth were not significantly different. Increasing the carbachol contact time 10-fold did not significantly influence the KB or the alpha value obtained with C7/3'-phth. Changing from Krebs to Tyrode solution did not significantly alter the KB for C7/3'-phth, although alpha values obtained were consistently lower in Tyrode solution, suggesting that the allosteric action may be sensitive to buffer composition. A 4-fold higher degree of negative, heterotropic co-operativity between C7/3'-phth and agonists than between C7/3'-phth and competitive antagonists was also found.

Decoding of top-down cognitive processing for SSVEP-controlled BMI

PubMed Central

Min, Byoung-Kyong; Dähne, Sven; Ahn, Min-Hee; Noh, Yung-Kyun; Müller, Klaus-Robert

2016-01-01

We present a fast and accurate non-invasive brain-machine interface (BMI) based on demodulating steady-state visual evoked potentials (SSVEPs) in electroencephalography (EEG). Our study reports an SSVEP-BMI that, for the first time, decodes primarily based on top-down and not bottom-up visual information processing. The experimental setup presents a grid-shaped flickering line array that the participants observe while intentionally attending to a subset of flickering lines representing the shape of a letter. While the flickering pixels stimulate the participant’s visual cortex uniformly with equal probability, the participant’s intention groups the strokes and thus perceives a ‘letter Gestalt’. We observed decoding accuracy of 35.81% (up to 65.83%) with a regularized linear discriminant analysis; on average 2.05-fold, and up to 3.77-fold greater than chance levels in multi-class classification. Compared to the EEG signals, an electrooculogram (EOG) did not significantly contribute to decoding accuracies. Further analysis reveals that the top-down SSVEP paradigm shows the most focalised activation pattern around occipital visual areas; Granger causality analysis consistently revealed prefrontal top-down control over early visual processing. Taken together, the present paradigm provides the first neurophysiological evidence for the top-down SSVEP BMI paradigm, which potentially enables multi-class intentional control of EEG-BMIs without using gaze-shifting. PMID:27808125

Sex differences in thickness, and folding developments throughout the cortex.

PubMed

Mutlu, A Kadir; Schneider, Maude; Debbané, Martin; Badoud, Deborah; Eliez, Stephan; Schaer, Marie

2013-11-15

While significant differences in male and female brain structures have commonly been reported, only a few studies have focused on the sex differences in the way the cortex matures over time. Here, we investigated cortical thickness maturation between the age of 6 to 30 years, using 209 longitudinally-acquired brain MRI scans. Significant sex differences in the trajectories of cortical thickness change with age were evidenced using non-linear mixed effects models. Similar statistical analyses were computed to quantify the differences between cortical gyrification changes with age in males and females. During adolescence, we observed a statistically significant higher rate of cortical thinning in females compared to males in the right temporal regions, the left temporoparietal junction and the left orbitofrontal cortex. This finding is interpreted as a faster maturation of the social brain areas in females. Concomitantly, statistically significant sex differences in cortical folding changes with age were observed only in one cluster of the right prefrontal regions, suggesting that the mechanisms underlying cortical thickness and gyrification changes with age are quite distinct. Sexual dimorphism in the developmental course of the cortical maturation may be associated with the different age of onset and clinical presentation of many psychiatric disorders between males and females. Copyright © 2013 Elsevier Inc. All rights reserved.

Decoding of top-down cognitive processing for SSVEP-controlled BMI

NASA Astrophysics Data System (ADS)

Min, Byoung-Kyong; Dähne, Sven; Ahn, Min-Hee; Noh, Yung-Kyun; Müller, Klaus-Robert

2016-11-01

We present a fast and accurate non-invasive brain-machine interface (BMI) based on demodulating steady-state visual evoked potentials (SSVEPs) in electroencephalography (EEG). Our study reports an SSVEP-BMI that, for the first time, decodes primarily based on top-down and not bottom-up visual information processing. The experimental setup presents a grid-shaped flickering line array that the participants observe while intentionally attending to a subset of flickering lines representing the shape of a letter. While the flickering pixels stimulate the participant’s visual cortex uniformly with equal probability, the participant’s intention groups the strokes and thus perceives a ‘letter Gestalt’. We observed decoding accuracy of 35.81% (up to 65.83%) with a regularized linear discriminant analysis; on average 2.05-fold, and up to 3.77-fold greater than chance levels in multi-class classification. Compared to the EEG signals, an electrooculogram (EOG) did not significantly contribute to decoding accuracies. Further analysis reveals that the top-down SSVEP paradigm shows the most focalised activation pattern around occipital visual areas; Granger causality analysis consistently revealed prefrontal top-down control over early visual processing. Taken together, the present paradigm provides the first neurophysiological evidence for the top-down SSVEP BMI paradigm, which potentially enables multi-class intentional control of EEG-BMIs without using gaze-shifting.

The relation between anxiety and BMI - is it all in our curves?

PubMed

Haghighi, Mohammad; Jahangard, Leila; Ahmadpanah, Mohammad; Bajoghli, Hafez; Holsboer-Trachsler, Edith; Brand, Serge

2016-01-30

The relation between anxiety and excessive weight is unclear. The aims of the present study were three-fold: First, we examined the association between anxiety and Body Mass Index (BMI). Second, we examined this association separately for female and male participants. Next, we examined both linear and non-linear associations between anxiety and BMI. The BMI was assessed of 92 patients (mean age: M=27.52; 57% females) suffering from anxiety disorders. Patients completed the Beck Anxiety Inventory. Both linear and non-linear correlations were computed for the sample as a whole and separately by gender. No gender differences were observed in anxiety scores or BMI. No linear correlation between anxiety scores and BMI was observed. In contrast, a non-linear correlation showed an inverted U-shaped association, with lower anxiety scores both for lower and very high BMI indices, and higher anxiety scores for medium to high BMI indices. Separate computations revealed no differences between males and females. The pattern of results suggests that the association between BMI and anxiety is complex and more accurately captured with non-linear correlations. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Radiometric Dating of Folds: A new approach to determine the timing of deformation at shallow-crustal conditions, with examples from the Mexican Fold-Thrust Belt

NASA Astrophysics Data System (ADS)

Fitz Diaz, E.; van der Pluijm, B. A.

2012-12-01

We are developing a robust method to obtain absolute ages of folds that were formed at shallow crustal conditions. The method takes advantage of illite neocrystallization in folded, clay-bearing layers and the ability to obtain accurate retention and total gas ages from small size fractions using encapsulated Ar analysis, analogous to prior work on fault gouge dating. We illustrate our approach in folded Cretaceous shale-bentonitic layers that are interbedded with carbonates of the Zimapán and the Tampico-Misantla cretaceous basins in central-eastern Mexico. Basinal carbonates were buried by syntectonic turbidites and inverted during the formation of the Mexican Fold-Thrust in the Late Cretaceous. Results were obtained from four chevron folds that are representative of different stages of deformation, burial/temperature conditions and location within this thin-skinned orogenic wedge: two from the Zimapán Basin (Folds 1 and 2) in the west and two from the Tampico-Misantla Basin (Folds 3 and 4) in the east. Mineralogic compositions and variations in illite-polytypes, crystallite-size (CS) and Ar/Ar ages were obtained from size fractions in limbs and hinges of folded layers. Ar retention ages produce a folding age of ~81 Ma for Fold 1 and ~69 Ma for Fold 2, which are fully consistent with stratigraphic limits from syn-orogenic turbidities and observed overprinting events in the Mexican Fold-Thrust Belt. The total gas age of Fold 3, on the easternmost margin of the Tampico-Misantla Basin is similar to that of Fold 2, indicating that the second event is regional in scale. In addition to presenting a new, reliable method to constrain the timing of local deformation, we interpret folding and associated clay neo-mineralization in terms of the regional burial history, and localization and propagation of deformation within a heterogeneous orogenic wedge involving progressive deformation of two basins separated by a platform block.

Ultrafast microfluidic mixer for tracking the early folding kinetics of human telomere G-quadruplex.

PubMed

Li, Ying; Liu, Chao; Feng, Xiaojun; Xu, Youzhi; Liu, Bi-Feng

2014-05-06

The folding of G-quadruplex is hypothesized to undergo a complex process, from the formation of a hairpin structure to a triplex intermediate and to the final G-quadruplex. Currently, no experimental evidence has been found for the hairpin formation, because it folds in the time regime of 10-100 μs, entailing the development of microfluidic mixers with a mixing time of less than 10 μs. In this paper, we reported an ultrarapid micromixer with a mixing time of 5.5 μs, which represents the fastest turbulent micromixer to our best knowledge. Evaluations of the micromixer were conducted to confirm its mixing efficiency for small molecules and macromolecules. This new micromixer enabled us to interrogate the hairpin formation in the early folding process of human telomere G-quadruplex. The experimental kinetic evidence for the formation of hairpin was obtained for the first time.

All-optical central-frequency-programmable and bandwidth-tailorable radar

PubMed Central

Zou, Weiwen; Zhang, Hao; Long, Xin; Zhang, Siteng; Cui, Yuanjun; Chen, Jianping

2016-01-01

Radar has been widely used for military, security, and rescue purposes, and modern radar should be reconfigurable at multi-bands and have programmable central frequencies and considerable bandwidth agility. Microwave photonics or photonics-assisted radio-frequency technology is a unique solution to providing such capabilities. Here, we demonstrate an all-optical central-frequency-programmable and bandwidth-tailorable radar architecture that provides a coherent system and utilizes one mode-locked laser for both signal generation and reception. Heterodyning of two individually filtered optical pulses that are pre-chirped via wavelength-to-time mapping generates a wideband linearly chirped radar signal. The working bands can be flexibly tailored with the desired bandwidth at a user-preferred carrier frequency. Radar echoes are first modulated onto the pre-chirped optical pulse, which is also used for signal generation, and then stretched in time or compressed in frequency several fold based on the time-stretch principle. Thus, digitization is facilitated without loss of detection ability. We believe that our results demonstrate an innovative radar architecture with an ultra-high-range resolution. PMID:26795596

Determination of acrosin activity of boar spermatozoa by the clinical method: optimization of the assay and changes during short-term storage of semen.

PubMed

Glogowski, J; Demianowicz, W; Piros, B; Ciereszko, A

1998-10-15

A clinical assay to evaluate total acrosin activity developed for human semen has been optimized for use in boar spermatozoa. The main modifications included a decrease of sperm number per assay from 1.0 to 10.0 x 10(6) to 12.5 to 75.0 x 10(3) spermatozoa, and the time of incubation from 180 to 60 min. Linearity of response for differing quantities of spermatozoa was maintained. Extensive washing of spermatozoa was necessary to eliminate seminal plasma, the source of acrosin inhibitors. Seminal plasma that was diluted 1000 times inhibited acrosin activity by about 50%. To abolish the inhibitory effect of seminal plasma it was necessary to use 25,000-fold dilution. Total acrosin activity of boar spermatozoa was about 100 times higher than that of human spermatozoa. Acrosin activity of boar spermatozoa in extended semen decreased during 7 d of storage. These results indicate that the clinical assay of acrosin activity can be used for boar spermatozoa to evaluate the quality of boar semen.

Fast-scale non-linear distortion analysis of peak-current-controlled buck-boost inverters

NASA Astrophysics Data System (ADS)

Zhang, Hao; Dong, Shuai; Yi, Chuanzhi; Guan, Weimin

2018-02-01

This paper deals with fast-scale non-linear distortion behaviours including asymmetrical period-doubling bifurcation and zero-crossing distortion in peak-current-controlled buck-boost inverters. The underlying mechanisms of the fast-scale non-linear distortion behaviours in inverters are revealed. The folded bifurcation diagram is presented to analyse the asymmetrical phenomenon of fast-scale period-doubling bifurcation. In view of the effect of phase shift and current ripple, the analytical expressions for one pair of critical phase angles are derived by using the design-oriented geometrical current approach. It is shown that the phase shift between inductor current and capacitor voltage should be responsible for the zero-crossing distortion phenomenon. These results obtained here are useful to optimise the circuit design and improve the circuit performance.

Precursory signatures of protein folding/unfolding: From time series correlation analysis to atomistic mechanisms

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

Hsu, P. J.; Lai, S. K., E-mail: sklai@coll.phy.ncu.edu.tw; Molecular Science and Technology Program, Taiwan International Graduate Program, Academia Sinica, Taipei 115, Taiwan

Folded conformations of proteins in thermodynamically stable states have long lifetimes. Before it folds into a stable conformation, or after unfolding from a stable conformation, the protein will generally stray from one random conformation to another leading thus to rapid fluctuations. Brief structural changes therefore occur before folding and unfolding events. These short-lived movements are easily overlooked in studies of folding/unfolding for they represent momentary excursions of the protein to explore conformations in the neighborhood of the stable conformation. The present study looks for precursory signatures of protein folding/unfolding within these rapid fluctuations through a combination of three techniques: (1)more » ultrafast shape recognition, (2) time series segmentation, and (3) time series correlation analysis. The first procedure measures the differences between statistical distance distributions of atoms in different conformations by calculating shape similarity indices from molecular dynamics simulation trajectories. The second procedure is used to discover the times at which the protein makes transitions from one conformation to another. Finally, we employ the third technique to exploit spatial fingerprints of the stable conformations; this procedure is to map out the sequences of changes preceding the actual folding and unfolding events, since strongly correlated atoms in different conformations are different due to bond and steric constraints. The aforementioned high-frequency fluctuations are therefore characterized by distinct correlational and structural changes that are associated with rate-limiting precursors that translate into brief segments. Guided by these technical procedures, we choose a model system, a fragment of the protein transthyretin, for identifying in this system not only the precursory signatures of transitions associated with α helix and β hairpin, but also the important role played by weaker correlations in such protein folding dynamics.« less

Precursory signatures of protein folding/unfolding: From time series correlation analysis to atomistic mechanisms

NASA Astrophysics Data System (ADS)

Hsu, P. J.; Cheong, S. A.; Lai, S. K.

2014-05-01

Folded conformations of proteins in thermodynamically stable states have long lifetimes. Before it folds into a stable conformation, or after unfolding from a stable conformation, the protein will generally stray from one random conformation to another leading thus to rapid fluctuations. Brief structural changes therefore occur before folding and unfolding events. These short-lived movements are easily overlooked in studies of folding/unfolding for they represent momentary excursions of the protein to explore conformations in the neighborhood of the stable conformation. The present study looks for precursory signatures of protein folding/unfolding within these rapid fluctuations through a combination of three techniques: (1) ultrafast shape recognition, (2) time series segmentation, and (3) time series correlation analysis. The first procedure measures the differences between statistical distance distributions of atoms in different conformations by calculating shape similarity indices from molecular dynamics simulation trajectories. The second procedure is used to discover the times at which the protein makes transitions from one conformation to another. Finally, we employ the third technique to exploit spatial fingerprints of the stable conformations; this procedure is to map out the sequences of changes preceding the actual folding and unfolding events, since strongly correlated atoms in different conformations are different due to bond and steric constraints. The aforementioned high-frequency fluctuations are therefore characterized by distinct correlational and structural changes that are associated with rate-limiting precursors that translate into brief segments. Guided by these technical procedures, we choose a model system, a fragment of the protein transthyretin, for identifying in this system not only the precursory signatures of transitions associated with α helix and β hairpin, but also the important role played by weaker correlations in such protein folding dynamics.

Effect of thyroid hormone concentration on the transcriptional response underlying induced metamorphosis in the Mexican axolotl (Ambystoma)

PubMed Central

Page, Robert B; Voss, Stephen R; Samuels, Amy K; Smith, Jeramiah J; Putta, Srikrishna; Beachy, Christopher K

2008-01-01

Background Thyroid hormones (TH) induce gene expression programs that orchestrate amphibian metamorphosis. In contrast to anurans, many salamanders do not undergo metamorphosis in nature. However, they can be induced to undergo metamorphosis via exposure to thyroxine (T4). We induced metamorphosis in juvenile Mexican axolotls (Ambystoma mexicanum) using 5 and 50 nM T4, collected epidermal tissue from the head at four time points (Days 0, 2, 12, 28), and used microarray analysis to quantify mRNA abundances. Results Individuals reared in the higher T4 concentration initiated morphological and transcriptional changes earlier and completed metamorphosis by Day 28. In contrast, initiation of metamorphosis was delayed in the lower T4 concentration and none of the individuals completed metamorphosis by Day 28. We identified 402 genes that were statistically differentially expressed by ≥ two-fold between T4 treatments at one or more non-Day 0 sampling times. To complement this analysis, we used linear and quadratic regression to identify 542 and 709 genes that were differentially expressed by ≥ two-fold in the 5 and 50 nM T4 treatments, respectively. Conclusion We found that T4 concentration affected the timing of gene expression and the shape of temporal gene expression profiles. However, essentially all of the identified genes were similarly affected by 5 and 50 nM T4. We discuss genes and biological processes that appear to be common to salamander and anuran metamorphosis, and also highlight clear transcriptional differences. Our results show that gene expression in axolotls is diverse and precise, and that axolotls provide new insights about amphibian metamorphosis. PMID:18267027

Effect of thyroid hormone concentration on the transcriptional response underlying induced metamorphosis in the Mexican axolotl (Ambystoma).

PubMed

Page, Robert B; Voss, Stephen R; Samuels, Amy K; Smith, Jeramiah J; Putta, Srikrishna; Beachy, Christopher K

2008-02-11

Thyroid hormones (TH) induce gene expression programs that orchestrate amphibian metamorphosis. In contrast to anurans, many salamanders do not undergo metamorphosis in nature. However, they can be induced to undergo metamorphosis via exposure to thyroxine (T4). We induced metamorphosis in juvenile Mexican axolotls (Ambystoma mexicanum) using 5 and 50 nM T4, collected epidermal tissue from the head at four time points (Days 0, 2, 12, 28), and used microarray analysis to quantify mRNA abundances. Individuals reared in the higher T4 concentration initiated morphological and transcriptional changes earlier and completed metamorphosis by Day 28. In contrast, initiation of metamorphosis was delayed in the lower T4 concentration and none of the individuals completed metamorphosis by Day 28. We identified 402 genes that were statistically differentially expressed by > or = two-fold between T4 treatments at one or more non-Day 0 sampling times. To complement this analysis, we used linear and quadratic regression to identify 542 and 709 genes that were differentially expressed by > or = two-fold in the 5 and 50 nM T4 treatments, respectively. We found that T4 concentration affected the timing of gene expression and the shape of temporal gene expression profiles. However, essentially all of the identified genes were similarly affected by 5 and 50 nM T4. We discuss genes and biological processes that appear to be common to salamander and anuran metamorphosis, and also highlight clear transcriptional differences. Our results show that gene expression in axolotls is diverse and precise, and that axolotls provide new insights about amphibian metamorphosis.

Direct numerical simulation of human phonation

NASA Astrophysics Data System (ADS)

Bodony, Daniel; Saurabh, Shakti

2017-11-01

The generation and propagation of the human voice in three-dimensions is studied using direct numerical simulation. A full body domain is employed for the purpose of directly computing the sound in the region past the speaker's mouth. The air in the vocal tract is modeled as a compressible and viscous fluid interacting with the elastic vocal folds. The vocal fold tissue material properties are multi-layered, with varying stiffness, and a linear elastic transversely isotropic model is utilized and implemented in a quadratic finite element code. The fluid-solid domains are coupled through a boundary-fitted interface and utilize a Poisson equation-based mesh deformation method. A kinematic constraint based on a specified minimum gap between the vocal folds is applied to prevent collision during glottal closure. Both near VF flow dynamics and far-field acoustics have been studied. A comparison is drawn to current two-dimensional simulations as well as to data from the literature. Near field vocal fold dynamics and glottal flow results are studied and in good agreement with previous three-dimensional phonation studies. Far-field acoustic characteristics, when compared to their two-dimensional counterpart, are shown to be sensitive to the dimensionality. Supported by the National Science Foundation (CAREER Award Number 1150439).

Extracting features from protein sequences to improve deep extreme learning machine for protein fold recognition.

PubMed

Ibrahim, Wisam; Abadeh, Mohammad Saniee

2017-05-21

Protein fold recognition is an important problem in bioinformatics to predict three-dimensional structure of a protein. One of the most challenging tasks in protein fold recognition problem is the extraction of efficient features from the amino-acid sequences to obtain better classifiers. In this paper, we have proposed six descriptors to extract features from protein sequences. These descriptors are applied in the first stage of a three-stage framework PCA-DELM-LDA to extract feature vectors from the amino-acid sequences. Principal Component Analysis PCA has been implemented to reduce the number of extracted features. The extracted feature vectors have been used with original features to improve the performance of the Deep Extreme Learning Machine DELM in the second stage. Four new features have been extracted from the second stage and used in the third stage by Linear Discriminant Analysis LDA to classify the instances into 27 folds. The proposed framework is implemented on the independent and combined feature sets in SCOP datasets. The experimental results show that extracted feature vectors in the first stage could improve the performance of DELM in extracting new useful features in second stage. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development and Validation of a Sensitive Method for Trace Nickel Determination by Slotted Quartz Tube Flame Atomic Absorption Spectrometry After Dispersive Liquid-Liquid Microextraction.

PubMed

Yolcu, Şükran Melda; Fırat, Merve; Chormey, Dotse Selali; Büyükpınar, Çağdaş; Turak, Fatma; Bakırdere, Sezgin

2018-05-01

In this study, dispersive liquid-liquid microextraction was systematically optimized for the preconcentration of nickel after forming a complex with diphenylcarbazone. The measurement output of the flame atomic absorption spectrometer was further enhanced by fitting a custom-cut slotted quartz tube to the flame burner head. The extraction method increased the amount of nickel reaching the flame and the slotted quartz tube increased the residence time of nickel atoms in the flame to record higher absorbance. Two methods combined to give about 90 fold enhancement in sensitivity over the conventional flame atomic absorption spectrometry. The optimized method was applicable over a wide linear concentration range, and it gave a detection limit of 2.1 µg L -1 . Low relative standard deviations at the lowest concentration in the linear calibration plot indicated high precision for both extraction process and instrumental measurements. A coal fly ash standard reference material (SRM 1633c) was used to determine the accuracy of the method, and experimented results were compatible with the certified value. Spiked recovery tests were also used to validate the applicability of the method.

Non-Linear Optical Microscopy Sheds Light on Cardiovascular Disease

PubMed Central

Caorsi, Valentina; Toepfer, Christopher; Sikkel, Markus B.; Lyon, Alexander R.; MacLeod, Ken; Ferenczi, Mike A.

2013-01-01

Many cardiac diseases have been associated with increased fibrosis and changes in the organization of fibrillar collagen. The degree of fibrosis is routinely analyzed with invasive histological and immunohistochemical methods, giving a limited and qualitative understanding of the tissue's morphological adaptation to disease. Our aim is to quantitatively evaluate the increase in fibrosis by three-dimensional imaging of the collagen network in the myocardium using the non-linear optical microscopy techniques Two-Photon Excitation microscopy (TPE) and Second Harmonic signal Generation (SHG). No sample staining is needed because numerous endogenous fluorophores are excited by a two-photon mechanism and highly non-centrosymmetric structures such as collagen generate strong second harmonic signals. We propose for the first time a 3D quantitative analysis to carefully evaluate the increased fibrosis in tissue from a rat model of heart failure post myocardial infarction. We show how to measure changes in fibrosis from the backward SHG (BSHG) alone, as only backward-propagating SHG is accessible for true in vivo applications. A 5-fold increase in collagen I fibrosis is detected in the remote surviving myocardium measured 20 weeks after infarction. The spatial distribution is also shown to change markedly, providing insight into the morphology of disease progression. PMID:23409139

Histological changes in vocal fold growth and aging.

PubMed

Kuhn, Maggie A

2014-12-01

Sophisticated descriptions of the highly specialized vocal fold microarchitecture have been available for over three decades, but how this anatomy evolves with growth and aging remains an area of active investigation and, at times, a source of controversy. As our aging population expands and interest in pediatric voice disorders blossoms, it is timely to consider our contemporary understanding of evolving vocal fold histology and its implications for voice production. Novel applications of existing and emerging biotechnology, development of animal models and skillful use of human specimens have afforded greater insights into the histologic vocal fold changes seen throughout the lifespan in health and disease. Burgeoning knowledge has laid the foundation for more comprehensive models of vocal fold histology and has led to the development of innovative therapies for challenging voice disorders.

Functional morphology of the Alligator mississippiensis larynx with implications for vocal production.

PubMed

Riede, Tobias; Li, Zhiheng; Tokuda, Isao T; Farmer, Colleen G

2015-04-01

Sauropsid vocalization is mediated by the syrinx in birds and the larynx in extant reptiles; but whereas avian vocal production has received much attention, the vocal mechanism of basal reptilians is poorly understood. The American alligator (Alligator mississippiensis) displays a large vocal repertoire during mating and in parent-offspring interactions. Although vocal outputs of these behaviors have received some attention, the underlying mechanism of sound production remains speculative. Here, we investigate the laryngeal anatomy of juvenile and adult animals by macroscopic and histological methods. Observations of the cartilaginous framework and associated muscles largely corroborate earlier findings, but one muscle, the cricoarytenoideus, exhibits a heretofore unknown extrinsic insertion that has important implications for effective regulation of vocal fold length and tension. Histological investigation of the larynx revealed a layered vocal fold morphology. The thick lamina propria consists of non-homogenous extracellular matrix containing collagen fibers that are tightly packed below the epithelium but loosely organized deep inside the vocal fold. We found few elastic fibers but comparatively high proportions of hyaluronan. Similar organizational complexity is also seen in mammalian vocal folds and the labia of the avian syrinx: convergent morphologies that suggest analogous mechanisms for sound production. In tensile tests, alligator vocal folds demonstrated a linear stress-strain behavior in the low strain region and nonlinear stress responses at strains larger than 15%, which is similar to mammalian vocal fold tissue. We have integrated morphological and physiological data in a two-mass vocal fold model, providing a systematic description of the possible acoustic space that could be available to an alligator larynx. Mapping actual call production onto possible acoustic space validates the model's predictions. © 2015. Published by The Company of Biologists Ltd.

Disruption of Higher-Order Folding by Core Histone Acetylation Dramatically Enhances Transcription of Nucleosomal Arrays by RNA Polymerase III

PubMed Central

Tse, Christin; Sera, Takashi; Wolffe, Alan P.; Hansen, Jeffrey C.

1998-01-01

We have examined the effects of core histone acetylation on the transcriptional activity and higher-order folding of defined 12-mer nucleosomal arrays. Purified HeLa core histone octamers containing an average of 2, 6, or 12 acetates per octamer (8, 23, or 46% maximal site occupancy, respectively) were assembled onto a DNA template consisting of 12 tandem repeats of a 208-bp Lytechinus 5S rRNA gene fragment. Reconstituted nucleosomal arrays were transcribed in a Xenopus oocyte nuclear extract and analyzed by analytical hydrodynamic and electrophoretic approaches to determine the extent of array compaction. Results indicated that in buffer containing 5 mM free Mg2+ and 50 mM KCl, high levels of acetylation (12 acetates/octamer) completely inhibited higher-order folding and concurrently led to a 15-fold enhancement of transcription by RNA polymerase III. The molecular mechanisms underlying the acetylation effects on chromatin condensation were investigated by analyzing the ability of differentially acetylated nucleosomal arrays to fold and oligomerize. In MgCl2-containing buffer the folding of 12-mer nucleosomal arrays containing an average of two or six acetates per histone octamer was indistinguishable, while a level of 12 acetates per octamer completely disrupted the ability of nucleosomal arrays to form higher-order folded structures at all ionic conditions tested. In contrast, there was a linear relationship between the extent of histone octamer acetylation and the extent of disruption of Mg2+-dependent oligomerization. These results have yielded new insight into the molecular basis of acetylation effects on both transcription and higher-order compaction of nucleosomal arrays. PMID:9671473

The dual-basin landscape in GFP folding

PubMed Central

Andrews, Benjamin T.; Gosavi, Shachi; Finke, John M.; Onuchic, José N.; Jennings, Patricia A.

2008-01-01

Recent experimental studies suggest that the mature GFP has an unconventional landscape composed of an early folding event with a typical funneled landscape, followed by a very slow search and rearrangement step into the locked, active chromophore-containing structure. As we have shown previously, the substantial difference in time scales is what generates the observed hysteresis in thermodynamic folding. The interconversion between locked and the soft folding structures at intermediate denaturant concentrations is so slow that it is not observed under the typical experimental observation time. Simulations of a coarse-grained model were used to describe the fast folding event as well as identify native-like intermediates on energy landscapes enroute to the fluorescent native fold. Interestingly, these simulations reveal structural features of the slow dynamic transition to chromophore activation. Experimental evidence presented here shows that the trapped, native-like intermediate has structural heterogeneity in residues previously linked to chromophore formation. We propose that the final step of GFP folding is a “locking” mechanism leading to chromophore formation and high stability. The combination of previous experimental work and current simulation work is explained in the context of a dual-basin folding mechanism described above. PMID:18713871

Trp zipper folding kinetics by molecular dynamics and temperature-jump spectroscopy

PubMed Central

Snow, Christopher D.; Qiu, Linlin; Du, Deguo; Gai, Feng; Hagen, Stephen J.; Pande, Vijay S.

2004-01-01

We studied the microsecond folding dynamics of three β hairpins (Trp zippers 1–3, TZ1–TZ3) by using temperature-jump fluorescence and atomistic molecular dynamics in implicit solvent. In addition, we studied TZ2 by using time-resolved IR spectroscopy. By using distributed computing, we obtained an aggregate simulation time of 22 ms. The simulations included 150, 212, and 48 folding events at room temperature for TZ1, TZ2, and TZ3, respectively. The all-atom optimized potentials for liquid simulations (OPLSaa) potential set predicted TZ1 and TZ2 properties well; the estimated folding rates agreed with the experimentally determined folding rates and native conformations were the global potential-energy minimum. The simulations also predicted reasonable unfolding activation enthalpies. This work, directly comparing large simulated folding ensembles with multiple spectroscopic probes, revealed both the surprising predictive ability of current models as well as their shortcomings. Specifically, for TZ1–TZ3, OPLS for united atom models had a nonnative free-energy minimum, and the folding rate for OPLSaa TZ3 was sensitive to the initial conformation. Finally, we characterized the transition state; all TZs fold by means of similar, native-like transition-state conformations. PMID:15020773

Trp zipper folding kinetics by molecular dynamics and temperature-jump spectroscopy

NASA Astrophysics Data System (ADS)

Snow, Christopher D.; Qiu, Linlin; Du, Deguo; Gai, Feng; Hagen, Stephen J.; Pande, Vijay S.

2004-03-01

We studied the microsecond folding dynamics of three hairpins (Trp zippers 1-3, TZ1-TZ3) by using temperature-jump fluorescence and atomistic molecular dynamics in implicit solvent. In addition, we studied TZ2 by using time-resolved IR spectroscopy. By using distributed computing, we obtained an aggregate simulation time of 22 ms. The simulations included 150, 212, and 48 folding events at room temperature for TZ1, TZ2, and TZ3, respectively. The all-atom optimized potentials for liquid simulations (OPLSaa) potential set predicted TZ1 and TZ2 properties well; the estimated folding rates agreed with the experimentally determined folding rates and native conformations were the global potential-energy minimum. The simulations also predicted reasonable unfolding activation enthalpies. This work, directly comparing large simulated folding ensembles with multiple spectroscopic probes, revealed both the surprising predictive ability of current models as well as their shortcomings. Specifically, for TZ1-TZ3, OPLS for united atom models had a nonnative free-energy minimum, and the folding rate for OPLSaa TZ3 was sensitive to the initial conformation. Finally, we characterized the transition state; all TZs fold by means of similar, native-like transition-state conformations.

High-Resolution Free-Energy Landscape Analysis of α-Helical Protein Folding: HP35 and Its Double Mutant

PubMed Central

2013-01-01

The free-energy landscape can provide a quantitative description of folding dynamics, if determined as a function of an optimally chosen reaction coordinate. Here, we construct the optimal coordinate and the associated free-energy profile for all-helical proteins HP35 and its norleucine (Nle/Nle) double mutant, based on realistic equilibrium folding simulations [Piana et al. Proc. Natl. Acad. Sci. U.S.A.2012, 109, 17845]. From the obtained profiles, we directly determine such basic properties of folding dynamics as the configurations of the minima and transition states (TS), the formation of secondary structure and hydrophobic core during the folding process, the value of the pre-exponential factor and its relation to the transition path times, the relation between the autocorrelation times in TS and minima. We also present an investigation of the accuracy of the pre-exponential factor estimation based on the transition-path times. Four different estimations of the pre-exponential factor for both proteins give k0–1 values of approximately a few tens of nanoseconds. Our analysis gives detailed information about folding of the proteins and can serve as a rigorous common language for extensive comparison between experiment and simulation. PMID:24348206

High-Resolution Free-Energy Landscape Analysis of α-Helical Protein Folding: HP35 and Its Double Mutant.

PubMed

Banushkina, Polina V; Krivov, Sergei V

2013-12-10

The free-energy landscape can provide a quantitative description of folding dynamics, if determined as a function of an optimally chosen reaction coordinate. Here, we construct the optimal coordinate and the associated free-energy profile for all-helical proteins HP35 and its norleucine (Nle/Nle) double mutant, based on realistic equilibrium folding simulations [Piana et al. Proc. Natl. Acad. Sci. U.S.A. 2012 , 109 , 17845]. From the obtained profiles, we directly determine such basic properties of folding dynamics as the configurations of the minima and transition states (TS), the formation of secondary structure and hydrophobic core during the folding process, the value of the pre-exponential factor and its relation to the transition path times, the relation between the autocorrelation times in TS and minima. We also present an investigation of the accuracy of the pre-exponential factor estimation based on the transition-path times. Four different estimations of the pre-exponential factor for both proteins give k 0 -1 values of approximately a few tens of nanoseconds. Our analysis gives detailed information about folding of the proteins and can serve as a rigorous common language for extensive comparison between experiment and simulation.

Morphoelastic control of gastro-intestinal organogenesis: Theoretical predictions and numerical insights

NASA Astrophysics Data System (ADS)

Balbi, V.; Kuhl, E.; Ciarletta, P.

2015-05-01

With nine meters in length, the gastrointestinal tract is not only our longest, but also our structurally most diverse organ. During embryonic development, it evolves as a bilayered tube with an inner endodermal lining and an outer mesodermal layer. Its inner surface displays a wide variety of morphological patterns, which are closely correlated to digestive function. However, the evolution of these intestinal patterns remains poorly understood. Here we show that geometric and mechanical factors can explain intestinal pattern formation. Using the nonlinear field theories of mechanics, we model surface morphogenesis as the instability problem of constrained differential growth. To allow for internal and external expansion, we model the gastrointestinal tract with homogeneous Neumann boundary conditions. To establish estimates for the folding pattern at the onset of folding, we perform a linear stability analysis supplemented by the perturbation theory. To predict pattern evolution in the post-buckling regime, we perform a series of nonlinear finite element simulations. Our model explains why longitudinal folds emerge in the esophagus with a thick and stiff outer layer, whereas circumferential folds emerge in the jejunum with a thinner and softer outer layer. In intermediate regions like the feline esophagus, longitudinal and circumferential folds emerge simultaneously. Our model could serve as a valuable tool to explain and predict alterations in esophageal morphology as a result of developmental disorders or certain digestive pathologies including food allergies.

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.

Erratum to: Clinical Pharmacokinetics of Sacubitril/Valsartan (LCZ696): A Novel Angiotensin Receptor-Neprilysin Inhibitor.

PubMed

Ayalasomayajula, Surya; Langenickel, Thomas; Pal, Parasar; Boggarapu, Sreedevi; Sunkara, Gangadhar

2018-01-01

Sacubitril/valsartan (LCZ696) is indicated for the treatment of heart failure with reduced ejection fraction. Absorption of sacubitril/valsartan and conversion of sacubitril (prodrug) to sacubitrilat (neprilysin inhibitor) was rapid with maximum plasma concentrations of sacubitril, sacubitrilat, and valsartan (angiotensin receptor blocker) reaching within 0.5, 1.5-2.0, and 2.0-3.0 h, respectively. With a twofold increase in dose, an increase in the area under the plasma concentration-time curve was proportional for sacubitril, ~1.9-fold for sacubitrilat, and ~1.7-fold for valsartan in healthy subjects. Following multiple twice-daily administration, steady-state maximum plasma concentration was reached within 3 days, showing no accumulation for sacubitril and valsartan, while ~1.6-fold accumulation for sacubitrilat. Sacubitril is eliminated predominantly as sacubitrilat through the kidney; valsartan is eliminated mainly by biliary route. Drug-drug interactions of sacubitril/valsartan were evaluated with medications commonly used in patients with heart failure including furosemide, warfarin, digoxin, carvedilol, levonorgestrel/ethinyl estradiol combination, amlodipine, omeprazole, hydrochlorothiazide, intravenous nitrates, metformin, statins, and sildenafil. Co-administration with sacubitril/valsartan increased the maximum plasma concentration (~2.0-fold) and area under the plasma concentration-time curve (1.3-fold) of atorvastatin; however, it did not affect the pharmacokinetics of simvastatin. Age, sex, or ethnicity did not affect the pharmacokinetics of sacubitril/valsartan. In patients with heart failure vs. healthy subjects, area under the plasma concentration-time curves of sacubitril, sacubitrilat, and valsartan were higher by approximately 1.6-, 2.1-, and 2.3-fold, respectively. Renal impairment had no significant impact on sacubitril and valsartan area under the plasma concentration-time curves, while the area under the plasma concentration-time curve of sacubitrilat correlated with degree of renal function (1.3-, 2.3-, 2.9-, and 3.3-fold with mild, moderate, and severe renal impairment, and end-stage renal disease, respectively). Moderate hepatic impairment increased the area under the plasma concentration-time curves of valsartan and sacubitrilat ~2.1-fold.

New Circuit QED system based on Triple-leg Stripline Resonator.

NASA Astrophysics Data System (ADS)

Kim, Dongmin; Moon, Kyungsun

Conventional circuit QED system consists of a qubit located inside a linear stripline resonator, which has successfully demonstrated a strong coupling between a single photon and a qubit. Here we present a new circuit QED system, where the qubit is coupled to triple-leg stripline resonator (TSR). We have shown that TSR supports two-fold degenerate photon modes among others. By coupling them to a single qubit, we have obtained the dressed states of a coupled system of a single qubit and two-fold degenerate photon modes. By locating two qubits at two legs of TSR, we have studied a potential two-bit gate operation (e.g., CNOT gate) of the system. We will discuss the main advantage of utilizing two-fold degenerate photon modes This work is partially supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2016R1D1A1B01013756).

Negative Coulomb damping, limit cycles, and self-oscillation of the vocal folds

NASA Astrophysics Data System (ADS)

Fulcher, Lewis P.; Scherer, Ronald C.; Melnykov, Artem; Gateva, Vesela; Limes, Mark E.

2006-05-01

An effective one-mass model of phonation is developed. It borrows the salient features of the classic two-mass model of human speech developed by Ishizaka, Matsudaira, and Flanagan. Their model is based on the idea that the oscillating vocal folds maintain their motion by deriving energy from the flow of air through the glottis. We argue that the essence of the action of the aerodynamic forces on the vocal folds is captured by negative Coulomb damping, which acts on the oscillator to energize it. A viscous force is added to include the effects of tissue damping. The solutions to this single oscillator model show that when it is excited by negative Coulomb damping, it will reach a limit cycle. Displacements, phase portraits, and energy histories are presented for two underdamped linear oscillators. A nonlinear force is added so that the variations of the fundamental frequency and the open quotient with lung pressure are comparable to the behavior of the two-mass model.

Modelled vs. reconstructed past fire dynamics - how can we compare?

NASA Astrophysics Data System (ADS)

Brücher, Tim; Brovkin, Victor; Kloster, Silvia; Marlon, Jennifer R.; Power, Mitch J.

2015-04-01

Fire is an important process that affects climate through changes in CO2 emissions, albedo, and aerosols (Ward et al. 2012). Fire-history reconstructions from charcoal accumulations in sediment indicate that biomass burning has increased since the Last Glacial Maximum (Power et al. 2008; Marlon et al. 2013). Recent comparisons with transient climate model output suggest that this increase in global ?re activity is linked primarily to variations in temperature and secondarily to variations in precipitation (Daniau et al. 2012). In this study, we discuss the best way to compare global ?re model output with charcoal records. Fire models generate quantitative output for burned area and fire-related emissions of CO2, whereas charcoal data indicate relative changes in biomass burning for specific regions and time periods only. However, models can be used to relate trends in charcoal data to trends in quantitative changes in burned area or fire carbon emissions. Charcoal records are often reported as Z-scores (Power et al. 2008). Since Z-scores are non-linear power transformations of charcoal influxes, we must evaluate if, for example, a two-fold increase in the standardized charcoal reconstruction corresponds to a 2- or 200-fold increase in the area burned. In our study we apply the Z-score metric to the model output. This allows us to test how well the model can quantitatively reproduce the charcoal-based reconstructions and how Z-score metrics affect the statistics of model output. The Global Charcoal Database (GCD version 2.5; www.gpwg.org/gpwgdb.html) is used to determine regional and global paleofire trends from 218 sedimentary charcoal records covering part or all of the last 8 ka BP. To retrieve regional and global composites of changes in fire activity over the Holocene the time series of Z-scores are linearly averaged to achieve regional composites. A coupled climate-carbon cycle model, CLIMBA (Brücher et al. 2014), is used for this study. It consists of the CLIMBER-2 Earth system model of intermediate complexity and the JSBACH land component of the Max Planck Institute Earth System Model. The fire algorithm in JSBACH assumes a constant annual lightning cycle as the sole fire ignition mechanism (Arora and Boer 2005). To eliminate data processing differences as a source for potential discrepancies, the processing of both reconstructed and modeled data, including e.g. normalisation with respect to a given base period and aggregation of time series was done in exactly the same way. Here, we compare the aggregated time series on a hemispheric and regional scale.

Classification for animal vocal fold surgery: resection margins impact histological outcomes of vocal fold injury.

PubMed

Imaizumi, Mitsuyoshi; Thibeault, Susan L; Leydon, Ciara

2014-11-01

Extent of vocal fold injury impacts the nature and timing of wound healing and voice outcomes. However, depth and extent of the lesion created to study wound healing in animal models vary across studies, likely contributing to different outcomes. Our goal was to create a surgery classification system to enable comparison of postoperative outcomes across animal vocal fold wound-healing studies. Prospective, controlled animal study. Rats underwent one of three types of unilateral vocal fold surgeries classified by depth and length of resection. The surgeries were: for subepithelial injury, resection of epithelium and superficial layer of the lamina propria at the midmembranous portion of the vocal fold; for transmucosal injury, resection of epithelium and lamina propria; and for transmuscular injury, resection of epithelium, lamina propria, and superficial portion of the vocalis muscle. Wound healing was evaluated histologically at various time points up to 35 days postinjury. Complete healing occurred by 14 days postsurgery for subepithelial injury, and by day 35 for transmucosal injury. Injury remained present at day 35 for transmuscular injury. Timing and completeness of healing varied by extent and depth of resection. Scarless healing occurred rapidly following subepithelial injury, whereas scarring was observed at 5 weeks after transmuscular injury. The proposed classification system may facilitate comparison of surgical outcomes across vocal fold wound-healing studies. N/A. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Protein folding: Over half a century lasting quest. Comment on "There and back again: Two views on the protein folding puzzle" by Alexei V. Finkelstein et al.

NASA Astrophysics Data System (ADS)

Krokhotin, Andrey; Dokholyan, Nikolay V.

2017-07-01

Most proteins fold into unique three-dimensional (3D) structures that determine their biological functions, such as catalytic activity or macromolecular binding. Misfolded proteins can pose a threat through aberrant interactions with other proteins leading to a number of diseases including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis [1,2]. What does determine 3D structure of proteins? The first clue to this question came more than fifty years ago when Anfinsen demonstrated that unfolded proteins can spontaneously fold to their native 3D structures [3,4]. Anfinsen's experiments lead to the conclusion that proteins fold to unique native structure corresponding to the stable and kinetically accessible free energy minimum, and protein native structure is solely determined by its amino acid sequence. The question of how exactly proteins find their free energy minimum proved to be a difficult problem. One of the puzzles, initially pointed out by Levinthal, was an inconsistency between observed protein folding times and theoretical estimates. A self-avoiding polymer model of a globular protein of 100-residues length on a cubic lattice can sample at least 1047 states. Based on the assumption that conformational sampling occurs at the highest vibrational mode of proteins (∼picoseconds), predicted folding time by searching among all the possible conformations leads to ∼1027 years (much larger than the age of the universe) [5]. In contrast, observed protein folding time range from microseconds to minutes. Due to tremendous theoretical progress in protein folding field that has been achieved in past decades, the source of this inconsistency is currently understood that is thoroughly described in the review by Finkelstein et al. [6].

First Passage Times, Lifetimes, and Relaxation Times of Unfolded Proteins

NASA Astrophysics Data System (ADS)

Dai, Wei; Sengupta, Anirvan M.; Levy, Ronald M.

2015-07-01

The dynamics of proteins in the unfolded state can be quantified in computer simulations by calculating a spectrum of relaxation times which describes the time scales over which the population fluctuations decay to equilibrium. If the unfolded state space is discretized, we can evaluate the relaxation time of each state. We derive a simple relation that shows the mean first passage time to any state is equal to the relaxation time of that state divided by the equilibrium population. This explains why mean first passage times from state to state within the unfolded ensemble can be very long but the energy landscape can still be smooth (minimally frustrated). In fact, when the folding kinetics is two-state, all of the unfolded state relaxation times within the unfolded free energy basin are faster than the folding time. This result supports the well-established funnel energy landscape picture and resolves an apparent contradiction between this model and the recently proposed kinetic hub model of protein folding. We validate these concepts by analyzing a Markov state model of the kinetics in the unfolded state and folding of the miniprotein NTL9 (where NTL9 is the N -terminal domain of the ribosomal protein L9), constructed from a 2.9 ms simulation provided by D. E. Shaw Research.

First Passage Times, Lifetimes, and Relaxation Times of Unfolded Proteins.

PubMed

Dai, Wei; Sengupta, Anirvan M; Levy, Ronald M

2015-07-24

The dynamics of proteins in the unfolded state can be quantified in computer simulations by calculating a spectrum of relaxation times which describes the time scales over which the population fluctuations decay to equilibrium. If the unfolded state space is discretized, we can evaluate the relaxation time of each state. We derive a simple relation that shows the mean first passage time to any state is equal to the relaxation time of that state divided by the equilibrium population. This explains why mean first passage times from state to state within the unfolded ensemble can be very long but the energy landscape can still be smooth (minimally frustrated). In fact, when the folding kinetics is two-state, all of the unfolded state relaxation times within the unfolded free energy basin are faster than the folding time. This result supports the well-established funnel energy landscape picture and resolves an apparent contradiction between this model and the recently proposed kinetic hub model of protein folding. We validate these concepts by analyzing a Markov state model of the kinetics in the unfolded state and folding of the miniprotein NTL9 (where NTL9 is the N-terminal domain of the ribosomal protein L9), constructed from a 2.9 ms simulation provided by D. E. Shaw Research.

Support vector machine and principal component analysis for microarray data classification

NASA Astrophysics Data System (ADS)

Astuti, Widi; Adiwijaya

2018-03-01

Cancer is a leading cause of death worldwide although a significant proportion of it can be cured if it is detected early. In recent decades, technology called microarray takes an important role in the diagnosis of cancer. By using data mining technique, microarray data classification can be performed to improve the accuracy of cancer diagnosis compared to traditional techniques. The characteristic of microarray data is small sample but it has huge dimension. Since that, there is a challenge for researcher to provide solutions for microarray data classification with high performance in both accuracy and running time. This research proposed the usage of Principal Component Analysis (PCA) as a dimension reduction method along with Support Vector Method (SVM) optimized by kernel functions as a classifier for microarray data classification. The proposed scheme was applied on seven data sets using 5-fold cross validation and then evaluation and analysis conducted on term of both accuracy and running time. The result showed that the scheme can obtained 100% accuracy for Ovarian and Lung Cancer data when Linear and Cubic kernel functions are used. In term of running time, PCA greatly reduced the running time for every data sets.

Design and 4D Printing of Cross-Folded Origami Structures: A Preliminary Investigation.

PubMed

Teoh, Joanne Ee Mei; An, Jia; Feng, Xiaofan; Zhao, Yue; Chua, Chee Kai; Liu, Yong

2018-03-03

In 4D printing research, different types of complex structure folding and unfolding have been investigated. However, research on cross-folding of origami structures (defined as a folding structure with at least two overlapping folds) has not been reported. This research focuses on the investigation of cross-folding structures using multi-material components along different axes and different horizontal hinge thickness with single homogeneous material. Tensile tests were conducted to determine the impact of multi-material components and horizontal hinge thickness. In the case of multi-material structures, the hybrid material composition has a significant impact on the overall maximum strain and Young's modulus properties. In the case of single material structures, the shape recovery speed is inversely proportional to the horizontal hinge thickness, while the flexural or bending strength is proportional to the horizontal hinge thickness. A hinge with a thickness of 0.5 mm could be folded three times prior to fracture whilst a hinge with a thickness of 0.3 mm could be folded only once prior to fracture. A hinge with a thickness of 0.1 mm could not even be folded without cracking. The introduction of a physical hole in the center of the folding/unfolding line provided stress relief and prevented fracture. A complex flower petal shape was used to successfully demonstrate the implementation of overlapping and non-overlapping folding lines using both single material segments and multi-material segments. Design guidelines for establishing cross-folding structures using multi-material components along different axes and different horizontal hinge thicknesses with single or homogeneous material were established. These guidelines can be used to design and implement complex origami structures with overlapping and non-overlapping folding lines. Combined overlapping folding structures could be implemented and allocating specific hole locations in the overall designs could be further explored. In addition, creating a more precise prediction by investigating sets of in between hinge thicknesses and comparing the folding times before fracture, will be the subject of future work.

Nonlinear graphene plasmonics

PubMed Central

2017-01-01

The rapid development of graphene has opened up exciting new fields in graphene plasmonics and nonlinear optics. Graphene's unique two-dimensional band structure provides extraordinary linear and nonlinear optical properties, which have led to extreme optical confinement in graphene plasmonics and ultrahigh nonlinear optical coefficients, respectively. The synergy between graphene's linear and nonlinear optical properties gave rise to nonlinear graphene plasmonics, which greatly augments graphene-based nonlinear device performance beyond a billion-fold. This nascent field of research will eventually find far-reaching revolutionary technological applications that require device miniaturization, low power consumption and a broad range of operating wavelengths approaching the far-infrared, such as optical computing, medical instrumentation and security applications. PMID:29118665

Nonlinear graphene plasmonics

NASA Astrophysics Data System (ADS)

Ooi, Kelvin J. A.; Tan, Dawn T. H.

2017-10-01

The rapid development of graphene has opened up exciting new fields in graphene plasmonics and nonlinear optics. Graphene's unique two-dimensional band structure provides extraordinary linear and nonlinear optical properties, which have led to extreme optical confinement in graphene plasmonics and ultrahigh nonlinear optical coefficients, respectively. The synergy between graphene's linear and nonlinear optical properties gave rise to nonlinear graphene plasmonics, which greatly augments graphene-based nonlinear device performance beyond a billion-fold. This nascent field of research will eventually find far-reaching revolutionary technological applications that require device miniaturization, low power consumption and a broad range of operating wavelengths approaching the far-infrared, such as optical computing, medical instrumentation and security applications.

Plane flame furnace combustion tests on JPL desulfurized coal

NASA Technical Reports Server (NTRS)

Reuther, J. J.; Kim, H. T.; Lima, J. G. H.

1982-01-01

The combustion characteristics of three raw bituminous (PSOC-282 and 276) and subbituminous (PSOC-230) coals, the raw coals partially desulfurized (ca -60%) by JPL chlorinolysis, and the chlorinated coals more completely desulfurized (ca -75%) by JPL hydrodesulfurization were determined. The extent to which the combustion characteristics of the untreated coals were altered upon JPL sulfur removal was examined. Combustion conditions typical of utility boilers were simulated in the plane flame furnace. Upon decreasing the parent coal voltaile matter generically by 80% and the sulfur by 75% via the JPL desulfurization process, ignition time was delayed 70 fold, burning velocity was retarded 1.5 fold, and burnout time was prolonged 1.4 fold. Total flame residence time increased 2.3 fold. The JPL desulfurization process appears to show significant promise for producing technologically combustible and clean burning (low SO3) fuels.

Dermal exposure and urinary 1-hydroxypyrene among asphalt roofing workers

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

McClean, M.D.; Rinehart, R.D.; Sapkota, A.

2007-07-01

The primary objective of this study was to identify significant determinants of dermal exposure to polycyclic aromatic compounds (PACs) among asphalt roofing workers and use urinary 1-hydroxyprene (1-OHP) measurements to evaluate the effect of dermal exposure on total absorbed dose. The study population included 26 asphalt roofing workers who performed three primary tasks: tearing off old roofs, putting down new roofs, and operating the kettle at ground level. During multiple consecutive work shifts, dermal patch samples were collected from the underside of each worker's wrists and were analyzed for PACs, pyrene, and benzo(a)pyrene (BAP). During the same work week, urinemore » samples were collected at pre-shift, post-shift, and bedtime each day and were analyzed for 1-OHP (205 urine samples). Linear mixed effects models were used to evaluate the dermal measurements for the purpose of identifying important determinants of exposure, and to evaluate urinary 1-OHP measurements for the purpose of identifying important determinants of total absorbed dose. Dermal exposures to PAC, pyrene, and BAP were found to vary significantly by roofing task and by the presence of an old coal tar pitch roof. For each of the three analytes, the adjusted mean dermal exposures associated with tear-off were approximately four times higher than exposures associated with operating the kettle. Exposure to coal tar pitch was associated with a 6-fold increase in PAC exposure, an 8-fold increase in pyrene exposure and a 35-fold increase in BAP exposure. The presence of coal tar pitch was the primary determinant of dermal exposure, particularly for exposure to BAP. However, the task-based differences that were observed while controlling for pitch suggest that exposure to asphalt also contributes to dermal exposures.« less

Dietary cadmium and benzo(a)pyrene increased intestinal metallothionein expression in the fish Fundulus heteroclitus

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

Roesijadi, Guritno; Rezvankhah, Saeid; Perez-Matus, Alejandro

2008-10-17

To test the effect of dietary exposure to cadmium and benzo(a)pyrene on induction of metallothionein mRNA in the Fundulus heteroclitus, fish were individually fed a pelletized gel food containing cadmium, benzo(a)pyrene, or a combination of the two over a period of seven days, then analyzed for relative levels of metallothionein mRNA in the intestine, liver, and gill using real-time RT-qPCR. An initial experiment with only cadmium exposure showed an apparent 10-fold induction in the intestine, but no induction in liver or gill. Ingestion of contaminated pellets varied in individual fish, and because it was possible to monitor individual ingestion ratesmore » with our method, individual cadmium doses were estimated from the amount of ingested cadmium. When the levels of metallothionein mRNA were related to the dose to each fish, a linear dose-response relationship was observed for the intestine, but not the other organs, which showed no induction. In a second experiment, dose was controlled by placing the entire daily cadmium dose into a single contaminated pellet that was fed first (thereby, effectively controlling the effect of variable ingestion rates), and the interaction between cadmium and benzo(a)pyrene was also investigated. The intestine was again the primary organ for metallothionein induction by cadmium, with a 20-fold increase in metallothionein mRNA over control levels. When benzo(a)pyrene was administered together with cadmium, induction of metallothionein was potentiated by the presence of benzo(a)pyrene, with the main effect seen in the intestine, where already high levels of induction by cadmium alone increased by 1.74-fold when benzo(a)pyrene was present.« less

Relationship Between the Electroglottographic Signal and Vocal Fold Contact Area.

PubMed

Hampala, Vít; Garcia, Maxime; Švec, Jan G; Scherer, Ronald C; Herbst, Christian T

2016-03-01

Electroglottography (EGG) is a widely used noninvasive method that purports to measure changes in relative vocal fold contact area (VFCA) during phonation. Despite its broad application, the putative direct relation between the EGG waveform and VFCA has to date only been formally tested in a single study, suggesting an approximately linear relationship. However, in that study, flow-induced vocal fold (VF) vibration was not investigated. A rigorous empirical evaluation of EGG as a measure of VFCA under proper physiological conditions is therefore still needed. Three red deer larynges were phonated in an excised hemilarynx preparation using a conducting glass plate. The time-varying contact between the VF and the glass plate was assessed by high-speed video recordings at 6000 fps, synchronized to the EGG signal. The average differences between the normalized [0, 1] VFCA and EGG waveforms for the three larynges were 0.180 (±0.156), 0.075 (±0.115), and 0.168 (±0.184) in the contacting phase and 0.159 (±0.112), -0.003 (±0.029), and 0.004 (±0.032) in the decontacting phase. Overall, there was a better agreement between VFCA and the EGG waveform in the decontacting phase than in the contacting phase. Disagreements may be caused by nonuniform tissue conductance properties, electrode placement, and electroglottograph hardware circuitry. Pending further research, the EGG waveform may be a reasonable first approximation to change in medial contact area between the VFs during phonation. However, any quantitative and statistical data derived from EGG should be interpreted cautiously, allowing for potential deviations from true VFCA. Copyright © 2016 The Auhors. Published by Elsevier Inc. All rights reserved.

Cytology of DNA Replication Reveals Dynamic Plasticity of Large-Scale Chromatin Fibers.

PubMed

Deng, Xiang; Zhironkina, Oxana A; Cherepanynets, Varvara D; Strelkova, Olga S; Kireev, Igor I; Belmont, Andrew S

2016-09-26

In higher eukaryotic interphase nuclei, the 100- to >1,000-fold linear compaction of chromatin is difficult to reconcile with its function as a template for transcription, replication, and repair. It is challenging to imagine how DNA and RNA polymerases with their associated molecular machinery would move along the DNA template without transient decondensation of observed large-scale chromatin "chromonema" fibers [1]. Transcription or "replication factory" models [2], in which polymerases remain fixed while DNA is reeled through, are similarly difficult to conceptualize without transient decondensation of these chromonema fibers. Here, we show how a dynamic plasticity of chromatin folding within large-scale chromatin fibers allows DNA replication to take place without significant changes in the global large-scale chromatin compaction or shape of these large-scale chromatin fibers. Time-lapse imaging of lac-operator-tagged chromosome regions shows no major change in the overall compaction of these chromosome regions during their DNA replication. Improved pulse-chase labeling of endogenous interphase chromosomes yields a model in which the global compaction and shape of large-Mbp chromatin domains remains largely invariant during DNA replication, with DNA within these domains undergoing significant movements and redistribution as they move into and then out of adjacent replication foci. In contrast to hierarchical folding models, this dynamic plasticity of large-scale chromatin organization explains how localized changes in DNA topology allow DNA replication to take place without an accompanying global unfolding of large-scale chromatin fibers while suggesting a possible mechanism for maintaining epigenetic programming of large-scale chromatin domains throughout DNA replication. Copyright © 2016 Elsevier Ltd. All rights reserved.

Factors influencing palmitoyl-CoA oxidation by rat liver peroxisomal fractions. Substrate concentration, organelle integrity and ATP.

PubMed Central

Thomas, J; Debeer, L J; De Schepper, P J; Mannaerts, G P

1980-01-01

1. The first dehydrogenation step of peroxisomal beta-oxidation involves the reduction of O2 to H2O2. Production rates of H2O2 and acetyl units by purified rat liver peroxisomes oxidizing palmitoyl-CoA were equal, indicating that H2O2 production is a reliable index for the release of acetyl units during peroxisomal fatty-acid oxidation. 2. Measurements of H2O2 and acid-soluble oxidation products during [1-14C]palmitoyl-CoA oxidation by purified peroxisomes revealed that the number of acetyl units released per molecule of palmitoyl-CoA oxidized rapidly decreased with increasing unbound palmitoyl-CoA concentrations. Structural damage to the peroxisomes caused by detergents or other treatments also decreased the number of acetyl units released. Under conditions where oxidation proceeded linearly with time the theoretical maximum of 5 acetyl units released per molecule of palmitoyl-CoA oxidized [Lazarow (1978) J. Biol. Chem. 253, 1522--1528] was never reached. 3. Expressed in terms of acetyl units produced and measured at low unbound-palmitoyl-CoA concentrations, mitochondrial oxidation was 10--20-fold higher than peroxisomal oxidation. 4. ATP stimulated peroxisomal palmitoyl-CoA oxidation approx. 2-fold. The ATP effect required the presence of Mg2+ and was lost when peroxisomal membranes were disrupted by Triton X-100 or high concentrations of unbound palmitoyl-CoA. 5. Disruption of peroxisomes by detergents, freeze--thawing, osmotic or mechanical treatment did not stimulate palmitoyl-CoA oxidation in the presence of ATP, indicating that peroxisomal fatty-acid-CoA oxidation was not latent. In the absence of ATP, Triton X-100 stimulated peroxisomal palmitoyl-CoA oxidation approx. 2-fold. PMID:7470063

Methodological and Epistemological Issues on Linear Regression Applied to Psychometric Variables in Problem Solving: Rethinking Variance

ERIC Educational Resources Information Center

Stamovlasis, Dimitrios

2010-01-01

The aim of the present paper is two-fold. First, it attempts to support previous findings on the role of some psychometric variables, such as, M-capacity, the degree of field dependence-independence, logical thinking and the mobility-fixity dimension, on students' achievement in chemistry problem solving. Second, the paper aims to raise some…

Development of electrochemical folic acid sensor based on hydroxyapatite nanoparticles

NASA Astrophysics Data System (ADS)

Kanchana, P.; Sekar, C.

2015-02-01

We report the synthesis of hydroxyapatite (HA) nanoparticles (NPs) by a simple microwave irradiation method and its application as sensing element for the precise determination of folic acid (FA) by electrochemical method. The structure and composition of the HA NPs characterized using XRD, FTIR, Raman and XPS. SEM and EDX studies confirmed the formation of elongated spherical shaped HA NPs with an average particle size of about 34 nm. The HA NPs thin film on glassy carbon electrode (GCE) were deposited by drop casting method. Electrocatalytic behavior of FA in the physiological pH 7.0 was investigated by cyclic voltammetry (CV), linear sweep voltammetry (LSV) and chronoamperometry. The fabricated HA/GCE exhibited a linear calibration plot over a wide FA concentration ranging from 1.0 × 10-7 to 3.5 × 10-4 M with the detection limit of 75 nM. In addition, the HA NPs modified GCE showed good selectivity toward the determination of FA even in the presence of a 100-fold excess of ascorbic acid (AA) and 1000-fold excess of other common interferents. The fabricated biosensor exhibits good sensitivity and stability, and was successfully applied for the determination of FA in pharmaceutical samples.

PDB to AMPL Conversion

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

Anna Johnston, SNL 9215

2002-09-01

PDB to AMPL Conversion was written to convert protein data base files to AMPL files. The protein data bases on the internet contain a wealth of information about the structue and makeup of proteins. Each file contains information derived by one or more experiments and contains information on how the experiment waw performed, the amino acid building blocks of each chain, and often the three-dimensional structure of the protein extracted from the experiments. The way a protein folds determines much about its function. Thus, studying the three-dimensional structure of the protein is of great interest. Analysing the contact maps ismore » one way to examine the structure. A contact map is a graph which has a linear back bone of amino acids for nodes (i.e., adjacent amino acids are always connected) and vertices between non-adjacent nodes if they are close enough to be considered in contact. If the graphs are similar then the folds of the protein and their function should also be similar. This software extracts the contact maps from a protein data base file and puts in into AMPL data format. This format is designed for use in AMPL, a programming language for simplifying linear programming formulations.« less

A stoichiometry driven universal spatial organization of backbones of folded proteins: are there Chargaff's rules for protein folding?

PubMed

Mittal, A; Jayaram, B; Shenoy, Sandhya; Bawa, Tejdeep Singh

2010-10-01

Protein folding is at least a six decade old problem, since the times of Pauling and Anfinsen. However, rules of protein folding remain elusive till date. In this work, rigorous analyses of several thousand crystal structures of folded proteins reveal a surprisingly simple unifying principle of backbone organization in protein folding. We find that protein folding is a direct consequence of a narrow band of stoichiometric occurrences of amino-acids in primary sequences, regardless of the size and the fold of a protein. We observe that "preferential interactions" between amino-acids do not drive protein folding, contrary to all prevalent views. We dedicate our discovery to the seminal contribution of Chargaff which was one of the major keys to elucidation of the stoichiometry-driven spatially organized double helical structure of DNA.

Winnowing DNA for rare sequences: highly specific sequence and methylation based enrichment.

PubMed

Thompson, Jason D; Shibahara, Gosuke; Rajan, Sweta; Pel, Joel; Marziali, Andre

2012-01-01

Rare mutations in cell populations are known to be hallmarks of many diseases and cancers. Similarly, differential DNA methylation patterns arise in rare cell populations with diagnostic potential such as fetal cells circulating in maternal blood. Unfortunately, the frequency of alleles with diagnostic potential, relative to wild-type background sequence, is often well below the frequency of errors in currently available methods for sequence analysis, including very high throughput DNA sequencing. We demonstrate a DNA preparation and purification method that through non-linear electrophoretic separation in media containing oligonucleotide probes, achieves 10,000 fold enrichment of target DNA with single nucleotide specificity, and 100 fold enrichment of unmodified methylated DNA differing from the background by the methylation of a single cytosine residue.

Transdermal Rivastigmine Delivery for Alzheimer Disease: Amenability of Exposure Predictions of Rivastigmine and Metabolite, NAP226-90, by Linear Regression Model Using Limited Samples.

PubMed

Srinivas, Nuggehally R

2016-01-01

Although an optimized delivery of rivastigmine for management of Alzhiemer disease (AD) is provided by the transdermal patch, it is critical to establish a limited sampling strategy for the measurement of exposure of rivastigmine/NAP226-90. The relationship Cmax versus AUC0-24h for rivastigmine/NAP226-90 was established by regression models. The derived regression equations enabled the prediction AUC0-24h for rivastigmine and NAP226-90. Models were evaluated using statistical criteria. Mixed model was used to predict AUC0-24h for rivastigmine/NAP226-90 from time points such as 8 (C8h), 12 (C12h), and 18 (C18h) hours. Excellent correlation was established for between Cmax and AUC0-24h for rivastigmine and NAP226-90. AUC0-24h predictions of either rivastigmine or NAP226-90 were within 0.8- to 1.25-fold difference. The RMSE in the AUC0-24h predictions ranged from 17.6% to 21.9%, and the R for prediction were greater than 0.96 for both rivastigmine and NAP226-90. Use of mixed model for C8h, C12h, and C18h resulted in AUC0-24h within 1.5-fold difference for rivastigmine or NAP226-90. Cmax of rivastigmine and NAP226-90 was highly correlated with the corresponding AUC0-24h values confirming the role of a time point closer to Cmax for an effective AUC measurement of rivastigmine or the metabolite.

“Retention Projection” Enables Reliable Use of Shared Gas Chromatographic Retention Data Across Labs, Instruments, and Methods

PubMed Central

Barnes, Brian B.; Wilson, Michael B.; Carr, Peter W.; Vitha, Mark F.; Broeckling, Corey D.; Heuberger, Adam L.; Prenni, Jessica; Janis, Gregory C.; Corcoran, Henry; Snow, Nicholas H.; Chopra, Shilpi; Dhandapani, Ramkumar; Tawfall, Amanda; Sumner, Lloyd W.; Boswell, Paul G.

2014-01-01

Gas chromatography-mass spectrometry (GC-MS) is a primary tool used to identify compounds in complex samples. Both mass spectra and GC retention times are matched to those of standards, but it is often impractical to have standards on hand for every compound of interest, so we must rely on shared databases of MS data and GC retention information. Unfortunately, retention databases (e.g. linear retention index libraries) are experimentally restrictive, notoriously unreliable, and strongly instrument dependent, relegating GC retention information to a minor, often negligible role in compound identification despite its potential power. A new methodology called “retention projection” has great potential to overcome the limitations of shared chromatographic databases. In this work, we tested the reliability of the methodology in five independent laboratories. We found that even when each lab ran nominally the same method, the methodology was 3-fold more accurate than retention indexing because it properly accounted for unintentional differences between the GC-MS systems. When the labs used different methods of their own choosing, retention projections were 4- to 165-fold more accurate. More importantly, the distribution of error in the retention projections was predictable across different methods and labs, thus enabling automatic calculation of retention time tolerance windows. Tolerance windows at 99% confidence were generally narrower than those widely used even when physical standards are on hand to measure their retention. With its high accuracy and reliability, the new retention projection methodology makes GC retention a reliable, precise tool for compound identification, even when standards are not available to the user. PMID:24205931

Severe Maternal Morbidity and Hospital Cost among Hospitalized Deliveries in the United States.

PubMed

Chen, Han-Yang; Chauhan, Suneet P; Blackwell, Sean C

2018-05-03

 The objective of this study was to estimate the contemporary national rate of severe maternal morbidity (SMM) and its associated hospital cost during delivery hospitalization.  We conducted a retrospective study identifying all delivery hospitalizations in the United States between 2011 and 2012. We used data from the National (Nationwide) Inpatient sample of the Healthcare Cost and Utilization Project. The delivery hospitalizations with SMM were identified by having at least one of the 25 previously established list of diagnosis and procedure codes. Aggregate and mean hospital costs were estimated. A generalized linear regression model was used to examine the association between SMM and hospital costs.  Of 7,438,946 delivery hospitalizations identified, the rate of SMM was 154 per 10,000 delivery hospitalizations. Without any SMM, the mean hospital cost was $4,300 and with any SMM, the mean hospital cost was $11,000. After adjustment, comparing to those without any SMM, the mean cost of delivery hospitalizations with any SMM was 2.1 (95% confidence interval: 2.1-2.2) times higher, and this ratio increases from 1.7-fold in those with only one SMM to 10.3-fold in those with five or more concurrent SMM.  The hospital cost with any SMM was 2.1 times higher than those without any SMM. Our findings highlight the need to identify interventions and guide research efforts to mitigate the rate of SMM and its economic burden. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Linear summation of outputs in a balanced network model of motor cortex.

PubMed

Capaday, Charles; van Vreeswijk, Carl

2015-01-01

Given the non-linearities of the neural circuitry's elements, we would expect cortical circuits to respond non-linearly when activated. Surprisingly, when two points in the motor cortex are activated simultaneously, the EMG responses are the linear sum of the responses evoked by each of the points activated separately. Additionally, the corticospinal transfer function is close to linear, implying that the synaptic interactions in motor cortex must be effectively linear. To account for this, here we develop a model of motor cortex composed of multiple interconnected points, each comprised of reciprocally connected excitatory and inhibitory neurons. We show how non-linearities in neuronal transfer functions are eschewed by strong synaptic interactions within each point. Consequently, the simultaneous activation of multiple points results in a linear summation of their respective outputs. We also consider the effects of reduction of inhibition at a cortical point when one or more surrounding points are active. The network response in this condition is linear over an approximately two- to three-fold decrease of inhibitory feedback strength. This result supports the idea that focal disinhibition allows linear coupling of motor cortical points to generate movement related muscle activation patterns; albeit with a limitation on gain control. The model also explains why neural activity does not spread as far out as the axonal connectivity allows, whilst also explaining why distant cortical points can be, nonetheless, functionally coupled by focal disinhibition. Finally, we discuss the advantages that linear interactions at the cortical level afford to motor command synthesis.

Solitons and protein folding: An In Silico experiment

NASA Astrophysics Data System (ADS)

Ilieva, N.; Dai, J.; Sieradzan, A.; Niemi, A.

2015-10-01

Protein folding [1] is the process of formation of a functional 3D structure from a random coil — the shape in which amino-acid chains leave the ribosome. Anfinsen's dogma states that the native 3D shape of a protein is completely determined by protein's amino acid sequence. Despite the progress in understanding the process rate and the success in folding prediction for some small proteins, with presently available physics-based methods it is not yet possible to reliably deduce the shape of a biologically active protein from its amino acid sequence. The protein-folding problem endures as one of the most important unresolved problems in science; it addresses the origin of life itself. Furthermore, a wrong fold is a common cause for a protein to lose its function or even endanger the living organism. Soliton solutions of a generalized discrete non-linear Schrödinger equation (GDNLSE) obtained from the energy function in terms of bond and torsion angles κ and τ provide a constructive theoretical framework for describing protein folds and folding patterns [2]. Here we study the dynamics of this process by means of molecular-dynamics simulations. The soliton manifestation is the pattern helix-loop-helix in the secondary structure of the protein, which explains the importance of understanding loop formation in helical proteins. We performed in silico experiments for unfolding one subunit of the core structure of gp41 from the HIV envelope glycoprotein (PDB ID: 1AIK [3]) by molecular-dynamics simulations with the MD package GROMACS. We analyzed 80 ns trajectories, obtained with one united-atom and two different all-atom force fields, to justify the side-chain orientation quantification scheme adopted in the studies and to eliminate force-field based artifacts. Our results are compatible with the soliton model of protein folding and provide first insight into soliton-formation dynamics.

High profile students’ growth of mathematical understanding in solving linier programing problems

NASA Astrophysics Data System (ADS)

Utomo; Kusmayadi, TA; Pramudya, I.

2018-04-01

Linear program has an important role in human’s life. This linear program is learned in senior high school and college levels. This material is applied in economy, transportation, military and others. Therefore, mastering linear program is useful for provision of life. This research describes a growth of mathematical understanding in solving linear programming problems based on the growth of understanding by the Piere-Kieren model. Thus, this research used qualitative approach. The subjects were students of grade XI in Salatiga city. The subjects of this study were two students who had high profiles. The researcher generally chose the subjects based on the growth of understanding from a test result in the classroom; the mark from the prerequisite material was ≥ 75. Both of the subjects were interviewed by the researcher to know the students’ growth of mathematical understanding in solving linear programming problems. The finding of this research showed that the subjects often folding back to the primitive knowing level to go forward to the next level. It happened because the subjects’ primitive understanding was not comprehensive.

Electrostatically Accelerated Encounter and Folding for Facile Recognition of Intrinsically Disordered Proteins

PubMed Central

Ganguly, Debabani; Zhang, Weihong; Chen, Jianhan

2013-01-01

Achieving facile specific recognition is essential for intrinsically disordered proteins (IDPs) that are involved in cellular signaling and regulation. Consideration of the physical time scales of protein folding and diffusion-limited protein-protein encounter has suggested that the frequent requirement of protein folding for specific IDP recognition could lead to kinetic bottlenecks. How IDPs overcome such potential kinetic bottlenecks to viably function in signaling and regulation in general is poorly understood. Our recent computational and experimental study of cell-cycle regulator p27 (Ganguly et al., J. Mol. Biol. (2012)) demonstrated that long-range electrostatic forces exerted on enriched charges of IDPs could accelerate protein-protein encounter via “electrostatic steering” and at the same time promote “folding-competent” encounter topologies to enhance the efficiency of IDP folding upon encounter. Here, we further investigated the coupled binding and folding mechanisms and the roles of electrostatic forces in the formation of three IDP complexes with more complex folded topologies. The surface electrostatic potentials of these complexes lack prominent features like those observed for the p27/Cdk2/cyclin A complex to directly suggest the ability of electrostatic forces to facilitate folding upon encounter. Nonetheless, similar electrostatically accelerated encounter and folding mechanisms were consistently predicted for all three complexes using topology-based coarse-grained simulations. Together with our previous analysis of charge distributions in known IDP complexes, our results support a prevalent role of electrostatic interactions in promoting efficient coupled binding and folding for facile specific recognition. These results also suggest that there is likely a co-evolution of IDP folded topology, charge characteristics, and coupled binding and folding mechanisms, driven at least partially by the need to achieve fast association kinetics for cellular signaling and regulation. PMID:24278008

In vivo engineering of the vocal fold extracellular matrix with injectable hyaluronic acid hydrogels: early effects on tissue repair and biomechanics in a rabbit model.

PubMed

Hansen, Jennifer K; Thibeault, Susan L; Walsh, Jennifer F; Shu, Xiao Zheng; Prestwich, Glenn D

2005-09-01

A prospective, controlled animal study was performed to determine whether the use of injectable, chemically modified hyaluronic acid (HA) derivatives at the time of intentional vocal fold resection might facilitate wound repair and preserve the unique viscoelastic properties of the vocal fold extracellular matrix. We performed bilateral vocal fold biopsies on 33 rabbits. Two groups of rabbits were unilaterally treated with 2 different HA derivatives--Carbylan-SX and HA-DTPH-PEGDA--at the time of resection. Saline was injected as a control into the contralateral fold. The animals were painlessly sacrificed 3 weeks after biopsy and injection. The outcomes measured included histologic fibrosis level, tissue HA level, and tissue viscosity and elasticity. The Carbylan-SX-treated vocal folds were found to have significantly less fibrosis than the saline-treated controls. The levels of HA in the treated vocal folds were not significantly different from those in the controls at 3 weeks as measured by enzyme-linked immunosorbent assay. The Carbylan-SX-treated vocal folds had significantly improved biomechanical properties of elasticity and viscosity. The HA-DTPH-PEGDA injections yielded significantly improved viscosity, but not elasticity. Prophylactic in vivo manipulation of the extracellular matrix with an injectable Carbylan-SX hydrogel appears to induce vocal fold tissue regeneration to yield optimal tissue composition and biomechanical properties favorable for phonation.

Fractional-wrapped branes with rotation, linear motion and background fields

NASA Astrophysics Data System (ADS)

Maghsoodi, Elham; Kamani, Davoud

2017-09-01

We obtain two boundary states corresponding to the two folds of a fractional-wrapped Dp-brane, i.e. the twisted version under the orbifold C2 /Z2 and the untwisted version. The brane has rotation and linear motion, in the presence of the following background fields: the Kalb-Ramond tensor, a U (1) internal gauge potential and a tachyon field. The rotation and linear motion are inside the volume of the brane. The brane lives in the d-dimensional spacetime, with the orbifold-toroidal structure Tn ×R 1 , d - n - 5 ×C2 /Z2 in the twisted sector. Using these boundary states we calculate the interaction amplitude of two parallel fractional Dp-branes with the foregoing setup. Various properties of this amplitude such as the long-range behavior will be analyzed.

Active control of multiple resistive wall modes

NASA Astrophysics Data System (ADS)

Brunsell, P. R.; Yadikin, D.; Gregoratto, D.; Paccagnella, R.; Liu, Y. Q.; Bolzonella, T.; Cecconello, M.; Drake, J. R.; Kuldkepp, M.; Manduchi, G.; Marchiori, G.; Marrelli, L.; Martin, P.; Menmuir, S.; Ortolani, S.; Rachlew, E.; Spizzo, G.; Zanca, P.

2005-12-01

A two-dimensional array of saddle coils at Mc poloidal and Nc toroidal positions is used on the EXTRAP T2R reversed-field pinch (Brunsell P R et al 2001 Plasma Phys. Control. Fusion 43 1457) to study active control of resistive wall modes (RWMs). Spontaneous growth of several RWMs with poloidal mode number m = 1 and different toroidal mode number n is observed experimentally, in agreement with linear MHD modelling. The measured plasma response to a controlled coil field and the plasma response computed using the linear circular cylinder MHD model are in quantitive agreement. Feedback control introduces a linear coupling of modes with toroidal mode numbers n, n' that fulfil the condition |n - n'| = Nc. Pairs of coupled unstable RWMs are present in feedback experiments with an array of Mc × Nc = 4 × 16 coils. Using intelligent shell feedback, the coupled modes are generally not controlled even though the field is suppressed at the active coils. A better suppression of coupled modes may be achieved in the case of rotating modes by using the mode control feedback scheme with individually set complex gains. In feedback with a larger array of Mc × Nc = 4 × 32 coils, the coupling effect largely disappears, and with this array, the main internal RWMs n = -11, -10, +5, +6 are all simultaneously suppressed throughout the discharge (7 8 wall times). With feedback there is a two-fold extension of the pulse length, compared to discharges without feedback.

In Vivo Engineering of the Vocal Fold ECM with Injectable HA Hydrogels -- Late Effects on Tissue Repair and Biomechanics in a Rabbit Model

PubMed Central

Klemuk, Sarah A.; Chen, Xia; Quinchia Johnson, Beatriz H.

2009-01-01

Objectives To determine if the utilization of injectable chemically-modified hyaluronan (HA) derivative at the time of intentional vocal fold resection may facilitate wound repair and preserve the unique viscoelastic properties of the extracellular matrix and lamina propria 6 months after treatment. Study Design Prospective, controlled animal study. Methods Twelve rabbit vocal folds were biopsied bilaterally, and the left side of vocal fold was treated with Extracel, an injectable, chemically-modified HA derivative, and the right side of vocal fold was injected with saline as control at the time of resection. Animals were sacrificed six months after biopsy and injection. Outcomes measured include transcription levels for procollagen, fibronectin, fibromodulin, TGF-β1, hyaluronan synthase and hyaluronidase and tissue biomechanics -- viscosity and elasticity. Results Extracel treated vocal folds were found to have significantly less fibrosis than saline treated controls. Extracel treated vocal folds had significantly improved biomechanical properties of elasticity and viscosity. Significantly decreased levels of fibronectin, fibromodulin, TGF-β1, procollagen I and hyaluronan synthase were measured. Conclusions Prophylactic in vivo manipulation of the extracellular matrix with an injectable HA hydrogel appears to induce vocal fold tissue regeneration to yield improved tissue composition and biomechanical properties at 6 months. PMID:20456912

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.

Space-time evolution of a growth fold (Betic Cordillera, Spain). Evidences from 3D geometrical modelling

NASA Astrophysics Data System (ADS)

Martin-Rojas, Ivan; Alfaro, Pedro; Estévez, Antonio

2014-05-01

We present a study that encompasses several software tools (iGIS©, ArcGIS©, Autocad©, etc.) and data (geological mapping, high resolution digital topographic data, high resolution aerial photographs, etc.) to create a detailed 3D geometric model of an active fault propagation growth fold. This 3D model clearly shows structural features of the analysed fold, as well as growth relationships and sedimentary patterns. The results obtained permit us to discuss the kinematics and structural evolution of the fold and the fault in time and space. The study fault propagation fold is the Crevillente syncline. This fold represents the northern limit of the Bajo Segura Basin, an intermontane basin in the Eastern Betic Cordillera (SE Spain) developed from upper Miocene on. 3D features of the Crevillente syncline, including growth pattern, indicate that limb rotation and, consequently, fault activity was higher during Messinian than during Tortonian; consequently, fault activity was also higher. From Pliocene on our data point that limb rotation and fault activity steadies or probably decreases. This in time evolution of the Crevillente syncline is not the same all along the structure; actually the 3D geometric model indicates that observed lateral heterogeneity is related to along strike variation of fault displacement.

Anthropometric and training variables related to half-marathon running performance in recreational female runners.

PubMed

Knechtle, Beat; Knechtle, Patrizia; Barandun, Ursula; Rosemann, Thomas

2011-05-01

The relationship between skin-fold thickness and running has been investigated in distances ranging from 100 m to the marathon distance (42.195 km), with the exclusion of the half-marathon distance (21.0975 km). We investigated the association between anthropometric variables, prerace experience, and training variables with race time in 42 recreational, nonprofessional, female half-marathon runners using bi- and multivariate analysis. Body weight (r, 0.60); body mass index (r, 0.48); body fat percentage (r, 0.56); pectoral (r, 0.61), mid-axilla (r, 0.69), triceps (r, 0.49), subscapular (r, 0.61), abdominal (r, 0.59), suprailiac (r, 0.55), and medial calf (r, 0.53) skin-fold thickness; mean speed of the training sessions (r, -0.68); and personal best time in a half-marathon (r, 0.69) correlated with race time after bivariate analysis. Body weight (P = 0.0054), pectoral skin-fold thickness (P = 0.0068), and mean speed of the training sessions (P = 0.0041) remained significant after multivariate analysis. Mean running speed during training was related to mid-axilla (r, -0.31), subscapular (r, -0.38), abdominal (r, -0.44), and suprailiac (r, -0.41) skin-fold thickness, the sum of 8 skin-fold thicknesses (r, -0.36); and percent body fat (r, -0.31). It was determined that variables of both anthropometry and training were related to half-marathon race time, and that skin-fold thicknesses were associated with running speed during training. For practical applications, high running speed during training (as opposed to extensive training) may both reduce upper-body skin-fold thicknesses and improve race performance in recreational female half-marathon runners.

Map showing the association of linear features with metallic mines and prospects in the Butte 1 degree by 2 degrees Quadrangle, Montana

USGS Publications Warehouse

Rowan, L.C.; Trautwein, C.M.; Purdy, T.L.

1990-01-01

This study was undertaken as part of the Conterminous U.S. Mineral Assessment Program (CUSMAP). The purpose of the study was to map linear features on Landsat Multispectral Scanner (MSS) images and a proprietary side-looking airborne radar (SLAR) image mosaic and to determine the spatial relationship between these linear features and the locations of metallic mineral occurrE-nces. The results show a close spatial association of linear features with metallic mineral occurrences in parts of the quadrangle, but in other areas the association is less well defined. Linear features are defined as distinct linear and slightly curvilinear elements mappable on MSS and SLAR images. The features generally represent linear segments of streams, ridges, and terminations of topographic features; however, they may also represent tonal patterns that are related to variations in lithology and vegetation. Most linear features in the Butte quadrangle probably represent underlying structural elements, such as fractures (with and without displacement), dikes, and alignment of fold axes. However, in areas underlain by sedimentary rocks, some of the linear features may reflect bedding traces. This report describes the geologic setting of the Butte quadrangle, the procedures used in mapping and analyzing the linear features, and the results of the study. Relationship of these features to placer and non-metal deposits were not analyzed in this study and are not discussed in this report.

Perfluoroalkyl Acids (PFAAs) in Serum from 2-4-Month-Old Infants: Influence of Maternal Serum Concentration, Gestational Age, Breast-Feeding, and Contaminated Drinking Water.

PubMed

Gyllenhammar, Irina; Benskin, Jonathan P; Sandblom, Oskar; Berger, Urs; Ahrens, Lutz; Lignell, Sanna; Wiberg, Karin; Glynn, Anders

2018-06-19

Little is known about factors influencing infant perfluorinated alkyl acid (PFAA) concentrations. Associations between serum PFAA concentrations in 2-4-month-old infants ( n = 101) and determinants were investigated by multiple linear regression and general linear model analysis. In exclusively breast-fed infants, maternal serum PFAA concentrations 3 weeks after delivery explained 13% (perfluoroundecanoic acid, PFUnDA) to 73% (perfluorohexanesulfonate, PFHxS) of infant PFAA concentration variation. Median infant/maternal ratios decreased with increasing PFAA carbon chain length from 2.8 for perfluoroheptanoic acid and perfluorooctanoic acid (PFOA) to 0.53 for PFUnDA and from 1.2 to 0.69 for PFHxS and perfluorooctanesulfonate (PFOS). Infant PFOA, perfluorononanoic acid (PFNA), and PFOS levels increased 0.7-1.2% per day of gestational age. Bottle-fed infants had mean concentrations of PFAAs 2 times lower than and a mean percentage of branched (%br) PFOS isomers 1.3 times higher than those of exclusively breast-fed infants. PFOA, PFNA, and PFHxS levels increased 8-11% per week of exclusive breast-feeding. Infants living in an area receiving PFAA-contaminated drinking water had 3-fold higher mean perfluorobutanesulfonate (PFBS) and PFHxS concentrations and higher mean %br PFHxS. Prenatal PFAA exposure and postnatal PFAA exposure significantly contribute to infant PFAA serum concentrations, depending on PFAA carbon chain length. Moderately PFBS- and PFHxS-contaminated drinking water is an important indirect exposure source.

Associations between time in bed and suicidal thoughts, plans and attempts in Korean adolescents

PubMed Central

Kim, Jae-Hyun; Park, Eun-Cheol; Lee, Sang Gyu; Yoo, Ki-Bong

2015-01-01

Objectives To examine the hypothesis that respondents with any of three specific sleep patterns would have a higher likelihood of suicidality than those without reports of these patterns in Korean adolescents. Setting Data from the 2011–2013 Korea Youth Risk Behavior Web-based Survey were used. Participants 191 642 subjects were included. The survey's target population was students in grades 7 through 12 in South Korea. Independent variable Sleep time. Primary and secondary outcome measures Suicidal thoughts, plans and attempts. Results The odds of suicidal thoughts in subjects with very short or long time in bed were 1.487-fold higher (95% CI 1.219 to 1.815) or 0.611-fold lower (95% CI 0.460 to 0.811), respectively, than for subjects with 7 h/day in bed; the odds were similar for suicidal plans. The odds of suicidal thoughts in subjects with early or late awakening times were 1.231-fold higher (95% CI 1.050 to 1.442) or 1.528-fold lower (95% CI 1.000 to 2.334), respectively, than for subjects with 7 h/day in bed; these odds were lower for suicidal plans and attempts. The odds of suicidal thoughts in subjects with early bedtime were 1.748-fold higher (95% CI 1.302 to 2.346), the odds of suicidal plans in people with an early bedtime were 2.494-fold higher (95% CI 1.671 to 3.722) and the odds of suicide attempts in subjects with late bedtime were 1.313-fold higher (95% CI 1.005 to 1.716) than for subjects with a bedtime of 23:00. Conclusions The sleep-related time is associated with suicide-related behaviours in Korean adolescents. Multilateral approaches are needed to identify the greatest risk factors for suicidal behaviours. PMID:26341585

Associations between time in bed and suicidal thoughts, plans and attempts in Korean adolescents.

PubMed

Kim, Jae-Hyun; Park, Eun-Cheol; Lee, Sang Gyu; Yoo, Ki-Bong

2015-09-04

To examine the hypothesis that respondents with any of three specific sleep patterns would have a higher likelihood of suicidality than those without reports of these patterns in Korean adolescents. Data from the 2011-2013 Korea Youth Risk Behavior Web-based Survey were used. 191,642 subjects were included. The survey's target population was students in grades 7 through 12 in South Korea. Sleep time. Suicidal thoughts, plans and attempts. The odds of suicidal thoughts in subjects with very short or long time in bed were 1.487-fold higher (95% CI 1.219 to 1.815) or 0.611-fold lower (95% CI 0.460 to 0.811), respectively, than for subjects with 7 h/day in bed; the odds were similar for suicidal plans. The odds of suicidal thoughts in subjects with early or late awakening times were 1.231-fold higher (95% CI 1.050 to 1.442) or 1.528-fold lower (95% CI 1.000 to 2.334), respectively, than for subjects with 7 h/day in bed; these odds were lower for suicidal plans and attempts. The odds of suicidal thoughts in subjects with early bedtime were 1.748-fold higher (95% CI 1.302 to 2.346), the odds of suicidal plans in people with an early bedtime were 2.494-fold higher (95% CI 1.671 to 3.722) and the odds of suicide attempts in subjects with late bedtime were 1.313-fold higher (95% CI 1.005 to 1.716) than for subjects with a bedtime of 23:00. The sleep-related time is associated with suicide-related behaviours in Korean adolescents. Multilateral approaches are needed to identify the greatest risk factors for suicidal behaviours. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Investigation of protein folding by coarse-grained molecular dynamics with the UNRES force field.

PubMed

Maisuradze, Gia G; Senet, Patrick; Czaplewski, Cezary; Liwo, Adam; Scheraga, Harold A

2010-04-08

Coarse-grained molecular dynamics simulations offer a dramatic extension of the time-scale of simulations compared to all-atom approaches. In this article, we describe the use of the physics-based united-residue (UNRES) force field, developed in our laboratory, in protein-structure simulations. We demonstrate that this force field offers about a 4000-times extension of the simulation time scale; this feature arises both from averaging out the fast-moving degrees of freedom and reduction of the cost of energy and force calculations compared to all-atom approaches with explicit solvent. With massively parallel computers, microsecond folding simulation times of proteins containing about 1000 residues can be obtained in days. A straightforward application of canonical UNRES/MD simulations, demonstrated with the example of the N-terminal part of the B-domain of staphylococcal protein A (PDB code: 1BDD, a three-alpha-helix bundle), discerns the folding mechanism and determines kinetic parameters by parallel simulations of several hundred or more trajectories. Use of generalized-ensemble techniques, of which the multiplexed replica exchange method proved to be the most effective, enables us to compute thermodynamics of folding and carry out fully physics-based prediction of protein structure, in which the predicted structure is determined as a mean over the most populated ensemble below the folding-transition temperature. By using principal component analysis of the UNRES folding trajectories of the formin-binding protein WW domain (PDB code: 1E0L; a three-stranded antiparallel beta-sheet) and 1BDD, we identified representative structures along the folding pathways and demonstrated that only a few (low-indexed) principal components can capture the main structural features of a protein-folding trajectory; the potentials of mean force calculated along these essential modes exhibit multiple minima, as opposed to those along the remaining modes that are unimodal. In addition, a comparison between the structures that are representative of the minima in the free-energy profile along the essential collective coordinates of protein folding (computed by principal component analysis) and the free-energy profile projected along the virtual-bond dihedral angles gamma of the backbone revealed the key residues involved in the transitions between the different basins of the folding free-energy profile, in agreement with existing experimental data for 1E0L .

Origami acoustics: using principles of folding structural acoustics for simple and large focusing of sound energy

NASA Astrophysics Data System (ADS)

Harne, Ryan L.; Lynd, Danielle T.

2016-08-01

Fixed in spatial distribution, arrays of planar, electromechanical acoustic transducers cannot adapt their wave energy focusing abilities unless each transducer is externally controlled, creating challenges for the implementation and portability of such beamforming systems. Recently, planar, origami-based structural tessellations are found to facilitate great versatility in system function and properties through kinematic folding. In this research we bridge the physics of acoustics and origami-based design to discover that the simple topological reconfigurations of a Miura-ori-based acoustic array yield many orders of magnitude worth of reversible change in wave energy focusing: a potential for acoustic field morphing easily obtained through deployable, tessellated architectures. Our experimental and theoretical studies directly translate the roles of folding the tessellated array to the adaptations in spectral and spatial wave propagation sensitivities for far field energy transmission. It is shown that kinematic folding rules and flat-foldable tessellated arrays collectively provide novel solutions to the long-standing challenges of conventional, electronically-steered acoustic beamformers. While our examples consider sound radiation from the foldable array in air, linear acoustic reciprocity dictates that the findings may inspire new innovations for acoustic receivers, e.g. adaptive sound absorbers and microphone arrays, as well as concepts that include water-borne waves.

Formulation and characterization of a porous, elastomeric biomaterial for vocal fold tissue engineering research

PubMed Central

Gaston, Joel; Bartlett, Rebecca S.; Klemuk, Sarah A.

2014-01-01

Objectives Biomaterials able to mimic the mechanical properties of vocal fold tissue may be particularly useful for furnishing three dimensional microenvironment allowing for in vitro investigation of cell and molecular responses to vibration. Motivated by the dearth of biomaterials available to be used in an in vitro model for vocal fold tissue, we investigated polyether polyurethane (PEU) matrices which are porous, mechanically tuneable biomaterials that are inexpensive and require only standard laboratory equipment for fabrication. Methods Rheology, dynamic mechanical analysis and scanning electron microscopy were performed on PEU matrices at 5%, 10% and 20% w/v mass concentrations. Results For 5%, 10%, and 20% w/v concentrations, shear storage modulus were 2 kPa, 3.4 kPa, and 6 kPa, respectively with shear loss modulus being 0.2 kPa, 0.38 kPa and 0.62 kPa, respectively. Storage modulus responded to applied frequency as a linear function. Mercury intrusion porosimetry revealed that all three mass concentrations of PEU have similar overall percent porosity, but differ in pore architecture. Conclusions 20 µm diameter pores are ideal for cell seeding, and range of mechanical properties indicates that the higher mass concentration PEU formulations are best suited for mimicking the viscoelastic properties of vocal fold tissue for in vitro research. PMID:24944281

First passage analysis of the folding of a β-sheet miniprotein: is it more realistic than the standard equilibrium approach?

PubMed

Kalgin, Igor V; Chekmarev, Sergei F; Karplus, Martin

2014-04-24

Simulations of first-passage folding of the antiparallel β-sheet miniprotein beta3s, which has been intensively studied under equilibrium conditions by A. Caflisch and co-workers, show that the kinetics and dynamics are significantly different from those for equilibrium folding. Because the folding of a protein in a living system generally corresponds to the former (i.e., the folded protein is stable and unfolding is a rare event), the difference is of interest. In contrast to equilibrium folding, the Ch-curl conformations become very rare because they contain unfavorable parallel β-strand arrangements, which are difficult to form dynamically due to the distant N- and C-terminal strands. At the same time, the formation of helical conformations becomes much easier (particularly in the early stage of folding) due to short-range contacts. The hydrodynamic descriptions of the folding reaction have also revealed that while the equilibrium flow field presented a collection of local vortices with closed "streamlines", the first-passage folding is characterized by a pronounced overall flow from the unfolded states to the native state. The flows through the locally stable structures Cs-or and Ns-or, which are conformationally close to the native state, are negligible due to detailed balance established between these structures and the native state. Although there are significant differences in the general picture of the folding process from the equilibrium and first-passage folding simulations, some aspects of the two are in agreement. The rate of transitions between the clusters of characteristic protein conformations in both cases decreases approximately exponentially with the distance between the clusters in the hydrogen bond distance space of collective variables, and the folding time distribution in the first-passage segments of the equilibrium trajectory is in good agreement with that for the first-passage folding simulations.

First Passage Analysis of the Folding of a β-Sheet Miniprotein: Is it More Realistic Than the Standard Equilibrium Approach?

PubMed Central

2015-01-01

Simulations of first-passage folding of the antiparallel β-sheet miniprotein beta3s, which has been intensively studied under equilibrium conditions by A. Caflisch and co-workers, show that the kinetics and dynamics are significantly different from those for equilibrium folding. Because the folding of a protein in a living system generally corresponds to the former (i.e., the folded protein is stable and unfolding is a rare event), the difference is of interest. In contrast to equilibrium folding, the Ch-curl conformations become very rare because they contain unfavorable parallel β-strand arrangements, which are difficult to form dynamically due to the distant N- and C-terminal strands. At the same time, the formation of helical conformations becomes much easier (particularly in the early stage of folding) due to short-range contacts. The hydrodynamic descriptions of the folding reaction have also revealed that while the equilibrium flow field presented a collection of local vortices with closed ”streamlines”, the first-passage folding is characterized by a pronounced overall flow from the unfolded states to the native state. The flows through the locally stable structures Cs-or and Ns-or, which are conformationally close to the native state, are negligible due to detailed balance established between these structures and the native state. Although there are significant differences in the general picture of the folding process from the equilibrium and first-passage folding simulations, some aspects of the two are in agreement. The rate of transitions between the clusters of characteristic protein conformations in both cases decreases approximately exponentially with the distance between the clusters in the hydrogen bond distance space of collective variables, and the folding time distribution in the first-passage segments of the equilibrium trajectory is in good agreement with that for the first-passage folding simulations. PMID:24669953

An Electrochemiluminescence Immunosensor Based on Gold-Magnetic Nanoparticles and Phage Displayed Antibodies

PubMed Central

Mu, Xihui; Tong, Zhaoyang; Huang, Qibin; Liu, Bing; Liu, Zhiwei; Hao, Lanqun; Dong, Hua; Zhang, Jinping; Gao, Chuan

2016-01-01

Using the multiple advantages of the ultra-highly sensitive electrochemiluminescence (ECL) technique, Staphylococcus protein A (SPA) functionalized gold-magnetic nanoparticles and phage displayed antibodies, and using gold-magnetic nanoparticles coated with SPA and coupled with a polyclonal antibody (pcAb) as magnetic capturing probes, and Ru(bpy)32+-labeled phage displayed antibody as a specific luminescence probe, this study reports a new way to detect ricin with a highly sensitive and specific ECL immunosensor and amplify specific detection signals. The linear detection range of the sensor was 0.0001~200 µg/L, and the limit of detection (LOD) was 0.0001 µg/L, which is 2500-fold lower than that of the conventional ELISA technique. The gold-magnetic nanoparticles, SPA and Ru(bpy)32+-labeled phage displayed antibody displayed different amplifying effects in the ECL immunosensor and can decrease LOD 3-fold, 3-fold and 20-fold, respectively, compared with the ECL immunosensors without one of the three effects. The integrated amplifying effect can decrease the LOD 180-fold. The immunosensor integrates the unique advantages of SPA-coated gold-magnetic nanoparticles that improve the activity of the functionalized capturing probe, and the amplifying effect of the Ru(bpy)32+-labeled phage displayed antibodies, so it increases specificity, interference-resistance and decreases LOD. It is proven to be well suited for the analysis of trace amounts of ricin in various environmental samples with high recovery ratios and reproducibility. PMID:26927130

Homeostasis of Hyaluronic Acid in Normal and Scarred Vocal Folds

PubMed Central

Tateya, Ichiro; Tateya, Tomoko; Watanuki, Makoto; Bless, Diane M.

2015-01-01

Summary Objectives/Hypothesis Vocal fold scarring is one of the most challenging laryngeal disorders to treat. Hyaluronic acid (HA) is the main component of lamina propria, and it plays an important role in proper vocal fold vibration and is also thought to be important in fetal wound healing without scarring. Although several animal models of vocal fold scarring have been reported, little is known about the way in which HA is maintained in vocal folds. The purpose of this study was to clarify the homeostasis of HA by examining the expression of hyaluronan synthase (Has) and hyaluronidase (Hyal), which produce and digest HA, respectively. Study Design Experimental prospective animal study. Methods Vocal fold stripping was performed on 38 Sprague-Dawley rats. Vocal fold tissue was collected at five time points (3 days–2 months). Expression of HA was examined by immunohistochemistry, and messenger RNA (mRNA) expression of Has and Hyal was examined by real-time polymerase chain reaction and in-situ hybridization. Results In scarred vocal folds, expression of Has1 and Has2 increased at day 3 together with expression of HA and returned to normal at 2 weeks. At 2 months, Has3 and Hyal3 mRNA showed higher expressions than normal. Conclusions Expression patterns of Has and Hyal genes differed between normal, acute-scarred, and chronic-scarred vocal folds, indicating the distinct roles of each enzyme in maintaining HA. Continuous upregulation of Has genes in the acute phase may be necessary to achieve scarless healing of vocal folds. PMID:25499520

Radiation Fibrosis of the Vocal Fold: From Man to Mouse

PubMed Central

Johns, Michael M.; Kolachala, Vasantha; Berg, Eric; Muller, Susan; Creighton, Frances X.; Branski, Ryan C.

2013-01-01

Objectives To characterize fundamental late tissue effects in the human vocal fold following radiation therapy. To develop a murine model of radiation fibrosis to ultimately develop both treatment and prevention paradigms. Design Translational study using archived human and fresh murine irradiated vocal fold tissue. Methods 1) Irradiated vocal fold tissue from patients undergoing laryngectomy for loss of function from radiation fibrosis were identified from pathology archives. Histomorphometry, immunohistochemistry, and whole-genome microarray as well as real-time transcriptional analyses was performed. 2) Focused radiation to the head and neck was delivered to mice in a survival fashion. One month following radiation, vocal fold tissue was analyzed with histomorphometry, immunohistochemistry, and real-time PCR transcriptional analysis for selected markers of fibrosis. Results Human irradiated vocal folds demonstrated increased collagen transcription with increased deposition and disorganization of collagen in both the thyroarytenoid muscle and the superficial lamina propria. Fibronectin were increased in the superficial lamina propria. Laminin decreased in the thyroarytenoid muscle. Whole genome microarray analysis demonstrated increased transcription of markers for fibrosis, oxidative stress, inflammation, glycosaminoglycan production and apoptosis. Irradiated murine vocal folds demonstrated increases in collagen and fibronectin transcription and deposition in the lamina propria. Transforming growth factor (TGF)-β increased in the lamina propria. Conclusion Human irradiated vocal folds demonstrate molecular changes leading to fibrosis that underlie loss of vocal fold pliability that occurs in patients following laryngeal irradiation. Irradiated murine tissue demonstrates similar findings, and this mouse model may have utility in creating prevention and treatment strategies for vocal fold radiation fibrosis. PMID:23242839

Kinetic pathway for folding of the Tetrahymena ribozyme revealed by three UV-inducible crosslinks.

PubMed Central

Downs, W D; Cech, T R

1996-01-01

The kinetics of RNA folding were examined in the L-21 ribozyme, an RNA enzyme derived from the self-splicing Tetrahymena intron. Three UV-inducible crosslinks were mapped, characterized, and used as indicators for the folded state of the ribozyme. Together these data suggest that final structures are adopted first by the P4-P6 independently folding domain and only later in a region that positions the P1 helix (including the 5' splice site), a region whose folding is linked to that of a portion of the catalytic core. At intermediate times, a non-native structure forms in the region of the triple helical scaffold, which connects the major folding domains. At 30 degrees C, the unfolded ribozyme passes through these stages with a half-life of 2 min from the time magnesium cations are provided. At higher temperatures, the half-life is shortened but the order of events is unchanged. Thermal melting of the fully folded ribozyme also revealed a multi-stage process in which the steps of folding are reversed: the kinetically slowest structure is the least stable and melts first. These structures of the ribozyme also bind Mg2+ cooperatively and their relative affinity for binding seems to be a major determinant in the order of events during folding. Na+ can also substitute for Mg2+ to give rise to the same crosslinkable structures, but only at much higher concentrations. Specific binding sites for Mg2+ may make this cation particularly efficient at electrostatic stabilization during folding of these ribozyme structures. PMID:8756414

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

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.

Long-term follow-up of vocal fold movement impairment and feeding after neonatal cardiac surgery.

PubMed

Richter, Amy Li; Ongkasuwan, Julina; Ocampo, Elena C

2016-04-01

To determine the long-term prognosis of children with vocal fold mobility impairment (VFMI) after cardiac surgery, with respect to time to normal feeding and incidence of admissions for pneumonia and feeding difficulties. A retrospective chart review was conducted of all neonates who had otolaryngology exam after cardiac surgery at a tertiary children's hospital from May 2007 to May 2008. Charts were reviewed for demographics, type of cardiac surgery, vocal fold mobility, diet at time of discharge and at last follow-up, time to full oral feeding, and hospital admissions. There were a total of 94 patients included in the study, 17 of whom had VFMI. While significantly more patients with VFMI required modified diet at discharge, 48% compared to 19% of patients with normal vocal fold mobility; there was no statistically significant difference in time to regular diet on long-term follow-up, 0.8 years (VFMI) compared to 0.4 years (normal vocal fold mobility). Of the 25 patients with modified diet or gastrostomy tube at discharge, 52% returned to full feeds within a year. There was no difference in hospitalizations for pneumonia in patients with or without VFMI. However in patients with VFMI, 35% required readmission for feeding difficulty or poor weight gain compared to only 5% in the infants with normal vocal fold mobility. After neonatal cardiac surgery, there do not appear to be long-term effects of VFMI with regards to readmission for pneumonia. However, there is an increased risk for hospitalization with respect to feeding difficulties in those neonates with VFMI. The overall prognosis for time to oral feeding is good. Copyright © 2016. Published by Elsevier Ireland Ltd.

Dynamic heterogeneity in the folding/unfolding transitions of FiP35

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

Mori, Toshifumi, E-mail: mori@ims.ac.jp; Saito, Shinji, E-mail: shinji@ims.ac.jp

Molecular dynamics simulations have become an important tool in studying protein dynamics over the last few decades. Atomistic simulations on the order of micro- to milliseconds are becoming feasible and are used to study the state-of-the-art experiments in atomistic detail. Yet, analyzing the high-dimensional-long-temporal trajectory data is still a challenging task and sometimes leads to contradictory results depending on the analyses. To reveal the dynamic aspect of the trajectory, here we propose a simple approach which uses a time correlation function matrix and apply to the folding/unfolding trajectory of FiP35 WW domain [Shaw et al., Science 330, 341 (2010)]. Themore » approach successfully characterizes the slowest mode corresponding to the folding/unfolding transitions and determines the free energy barrier indicating that FiP35 is not an incipient downhill folder. The transition dynamics analysis further reveals that the folding/unfolding transition is highly heterogeneous, e.g., the transition path time varies by ∼100 fold. We identify two misfolded states and show that the dynamic heterogeneity in the folding/unfolding transitions originates from the trajectory being trapped in the misfolded and half-folded intermediate states rather than the diffusion driven by a thermal noise. The current results help reconcile the conflicting interpretations of the folding mechanism and highlight the complexity in the folding dynamics. This further motivates the need to understand the transition dynamics beyond a simple free energy picture using simulations and single-molecule experiments.« less

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 Fault-Propagation Folds with Variable Interlimb Angles

NASA Astrophysics Data System (ADS)

Dhont, D.; Jabbour, M.; Hervouet, Y.; Deroin, J.

2009-12-01

Fault-propagation folds are common features in foreland basins and fold-and-thrust belts. Several conceptual models have been proposed to account for their geometry and kinematics. It is generally accepted that the shape of fault-propagation folds depends directly from both the amount of displacement along the basal decollement level and the dip angle of the ramp. Among these, the variable interlimb angle model proposed by Mitra (1990) is based on a folding kinematics that is able to explain open and close natural folds. However, the application of this model is limited because the geometric evolution and thickness variation of the fold directly depend on imposed parameters such as the maximal value of the ramp height. Here, we use the ramp and the interlimb angles as input data to develop a forward fold modelling accounting for thickness variations in the forelimb. The relationship between the fold amplitude and fold wavelength are subsequently applied to build balanced geologic cross-sections from surface parameters only, and to propose a kinematic restoration of the folding through time. We considered three natural examples to validate the variable interlimb angle model. Observed thickness variations in the forelimb of the Turner Valley anticline in the Alberta foothills of Canada precisely correspond to the theoretical values proposed by our model. Deep reconstruction of the Alima anticline in the southern Tunisian Atlas implies that the decollement level is localized in the Triassic-Liassic series, as highlighted by seismic imaging. Our kinematic reconstruction of the Ucero anticline in the Spanish Castilian mountains is also in agreement with the anticline geometry derived from two cross-sections. The variable interlimb angle model implies that the fault-propagation fold can be symmetric, normal asymmetric (with a greater dip value in the forelimb than in the backlimb), or reversely asymmetric (with greater dip in the backlimb) depending on the shortening amount. This model allows also: (i) to easily explain folds with wide variety of geometries; (ii) to understand the deep architecture of anticlines; and (iii) to deduce the kinematic evolution of folding with time. Mitra, S., 1990, Fault-propagation folds: geometry, kinematic evolution, and hydrocarbon traps. AAPG Bulletin, v. 74, no. 6, p. 921-945.

Design and 4D Printing of Cross-Folded Origami Structures: A Preliminary Investigation

PubMed Central

Teoh, Joanne Ee Mei; Feng, Xiaofan; Zhao, Yue; Liu, Yong

2018-01-01

In 4D printing research, different types of complex structure folding and unfolding have been investigated. However, research on cross-folding of origami structures (defined as a folding structure with at least two overlapping folds) has not been reported. This research focuses on the investigation of cross-folding structures using multi-material components along different axes and different horizontal hinge thickness with single homogeneous material. Tensile tests were conducted to determine the impact of multi-material components and horizontal hinge thickness. In the case of multi-material structures, the hybrid material composition has a significant impact on the overall maximum strain and Young’s modulus properties. In the case of single material structures, the shape recovery speed is inversely proportional to the horizontal hinge thickness, while the flexural or bending strength is proportional to the horizontal hinge thickness. A hinge with a thickness of 0.5 mm could be folded three times prior to fracture whilst a hinge with a thickness of 0.3 mm could be folded only once prior to fracture. A hinge with a thickness of 0.1 mm could not even be folded without cracking. The introduction of a physical hole in the center of the folding/unfolding line provided stress relief and prevented fracture. A complex flower petal shape was used to successfully demonstrate the implementation of overlapping and non-overlapping folding lines using both single material segments and multi-material segments. Design guidelines for establishing cross-folding structures using multi-material components along different axes and different horizontal hinge thicknesses with single or homogeneous material were established. These guidelines can be used to design and implement complex origami structures with overlapping and non-overlapping folding lines. Combined overlapping folding structures could be implemented and allocating specific hole locations in the overall designs could be further explored. In addition, creating a more precise prediction by investigating sets of in between hinge thicknesses and comparing the folding times before fracture, will be the subject of future work. PMID:29510503

Estimating Genomic Distance from DNA Sequence Location in Cell Nuclei by a Random Walk Model

NASA Astrophysics Data System (ADS)

van den Engh, Ger; Sachs, Rainer; Trask, Barbara J.

1992-09-01

The folding of chromatin in interphase cell nuclei was studied by fluorescent in situ hybridization with pairs of unique DNA sequence probes. The sites of DNA sequences separated by 100 to 2000 kilobase pairs (kbp) are distributed in interphase chromatin according to a random walk model. This model provides the basis for calculating the spacing of sequences along the linear DNA molecule from interphase distance measurements. An interphase mapping strategy based on this model was tested with 13 probes from a 4-megabase pair (Mbp) region of chromosome 4 containing the Huntington disease locus. The results confirmed the locations of the probes and showed that the remaining gap in the published maps of this region is negligible in size. Interphase distance measurements should facilitate construction of chromosome maps with an average marker density of one per 100 kbp, approximately ten times greater than that achieved by hybridization to metaphase chromosomes.

Dark energy in the dark ages

NASA Astrophysics Data System (ADS)

Linder, Eric V.

2006-08-01

Non-negligible dark energy density at high redshifts would indicate dark energy physics distinct from a cosmological constant or "reasonable" canonical scalar fields. Such dark energy can be constrained tightly through investigation of the growth of structure, with limits of ≲2% of total energy density at z ≫ 1 for many models. Intermediate dark energy can have effects distinct from its energy density; the dark ages acceleration can be constrained to last less than 5% of a Hubble e-fold time, exacerbating the coincidence problem. Both the total linear growth, or equivalently σ8, and the shape and evolution of the nonlinear mass power spectrum for z < 2 (using the Linder-White nonlinear mapping prescription) provide important windows. Probes of growth, such as weak gravitational lensing, can interact with supernovae and CMB distance measurements to scan dark energy behavior over the entire range z = 0-1100.

Low-memory iterative density fitting.

PubMed

Grajciar, Lukáš

2015-07-30

A new low-memory modification of the density fitting approximation based on a combination of a continuous fast multipole method (CFMM) and a preconditioned conjugate gradient solver is presented. Iterative conjugate gradient solver uses preconditioners formed from blocks of the Coulomb metric matrix that decrease the number of iterations needed for convergence by up to one order of magnitude. The matrix-vector products needed within the iterative algorithm are calculated using CFMM, which evaluates them with the linear scaling memory requirements only. Compared with the standard density fitting implementation, up to 15-fold reduction of the memory requirements is achieved for the most efficient preconditioner at a cost of only 25% increase in computational time. The potential of the method is demonstrated by performing density functional theory calculations for zeolite fragment with 2592 atoms and 121,248 auxiliary basis functions on a single 12-core CPU workstation. © 2015 Wiley Periodicals, Inc.

Instability of g-mode oscillations in white dwarf stars

NASA Technical Reports Server (NTRS)

Keeley, D. A.

1979-01-01

A white dwarf model with M = 6 solar masses, Te = 12,000 K, and L = 1.2 x 10 to the 31st erg/sec provided by Cox has been tested for linear stability of radial oscillations. The radial mode instability first reported for this model by Cox, et al. (1979) has been confirmed. The growth rates obtained are comparable to the rates found by Cox. A sequence of l = 2 g-modes has also been found to be unstable. The e-folding times range from around 10 to the 11th periods for a 137 second mode (1 radial node) to less than 100 periods for a 629 second mode (17 nodes). It is likely that the latter rate is too high because the eigenfunction has been forced to vanish at the non-zero inner radius of the model, at which the Brunt-Vaisala frequency is barely less than the mode frequency.

A computational study of crimping and expansion of bioresorbable polymeric stents

NASA Astrophysics Data System (ADS)

Qiu, T. Y.; Song, M.; Zhao, L. G.

2018-05-01

This paper studied the mechanical performance of four bioresorbable PLLA stents, i.e., Absorb, Elixir, Igaki-Tamai and RevaMedical, during crimping and expansion using the finite element method. Abaqus CAE was used to create the geometrical models for the four stents. A tri-folded balloon was created using NX software. For the stents, elastic-plastic behaviour was used, with hardening implemented by considering the increase of yield stress with the plastic strain. The tri-folded balloon was treated as linear elastic. To simulate the crimping of stents, a set of 12 rigid plates were generated around the stents with a radially enforced displacement. During crimping, the stents were compressed from a diameter of 3 mm to 1.2 mm, with the maximum stress developed at both inner and outer sides of the U-bends. During expansion, the stent inner diameter increased to 3 mm at the peak pressure and then recoiled to different final diameters after balloon deflation due to different stent designs. The maximum stress was found again at the U-bends of stents. Diameter change, recoiling effect and radial strength/stiffness were also compared for the four stents to assess the effect of design variation on stent performance. The effect of loading rate on stent deformation was also simulated by considering the time-dependent plastic behaviour of polymeric material.

A computational study of crimping and expansion of bioresorbable polymeric stents

NASA Astrophysics Data System (ADS)

Qiu, T. Y.; Song, M.; Zhao, L. G.

2017-10-01

This paper studied the mechanical performance of four bioresorbable PLLA stents, i.e., Absorb, Elixir, Igaki-Tamai and RevaMedical, during crimping and expansion using the finite element method. Abaqus CAE was used to create the geometrical models for the four stents. A tri-folded balloon was created using NX software. For the stents, elastic-plastic behaviour was used, with hardening implemented by considering the increase of yield stress with the plastic strain. The tri-folded balloon was treated as linear elastic. To simulate the crimping of stents, a set of 12 rigid plates were generated around the stents with a radially enforced displacement. During crimping, the stents were compressed from a diameter of 3 mm to 1.2 mm, with the maximum stress developed at both inner and outer sides of the U-bends. During expansion, the stent inner diameter increased to 3 mm at the peak pressure and then recoiled to different final diameters after balloon deflation due to different stent designs. The maximum stress was found again at the U-bends of stents. Diameter change, recoiling effect and radial strength/stiffness were also compared for the four stents to assess the effect of design variation on stent performance. The effect of loading rate on stent deformation was also simulated by considering the time-dependent plastic behaviour of polymeric material.

An anthropometric model to estimate neonatal fat mass using air displacement plethysmography

PubMed Central

2012-01-01

Background Current validated neonatal body composition methods are limited/impractical for use outside of a clinical setting because they are labor intensive, time consuming, and require expensive equipment. The purpose of this study was to develop an anthropometric model to estimate neonatal fat mass (kg) using an air displacement plethysmography (PEA POD® Infant Body Composition System) as the criterion. Methods A total of 128 healthy term infants, 60 females and 68 males, from a multiethnic cohort were included in the analyses. Gender, race/ethnicity, gestational age, age (in days), anthropometric measurements of weight, length, abdominal circumference, skin-fold thicknesses (triceps, biceps, sub scapular, and thigh), and body composition by PEA POD® were collected within 1-3 days of birth. Backward stepwise linear regression was used to determine the model that best predicted neonatal fat mass. Results The statistical model that best predicted neonatal fat mass (kg) was: -0.012 -0.064*gender + 0.024*day of measurement post-delivery -0.150*weight (kg) + 0.055*weight (kg)2 + 0.046*ethnicity + 0.020*sum of three skin-fold thicknesses (triceps, sub scapular, and thigh); R2 = 0.81, MSE = 0.08 kg. Conclusions Our anthropometric model explained 81% of the variance in neonatal fat mass. Future studies with a greater variety of neonatal anthropometric measurements may provide equations that explain more of the variance. PMID:22436534

A specific transition state for S-peptide combining with folded S-protein and then refolding

PubMed Central

Goldberg, Jonathan M.; Baldwin, Robert L.

1999-01-01

We measured the folding and unfolding kinetics of mutants for a simple protein folding reaction to characterize the structure of the transition state. Fluorescently labeled S-peptide analogues combine with S-protein to form ribonuclease S analogues: initially, S-peptide is disordered whereas S-protein is folded. The fluorescent probe provides a convenient spectroscopic probe for the reaction. The association rate constant, kon, and the dissociation rate constant, koff, were both determined for two sets of mutants. The dissociation rate constant is measured by adding an excess of unlabeled S-peptide analogue to a labeled complex (RNaseS*). This strategy allows kon and koff to be measured under identical conditions so that microscopic reversibility applies and the transition state is the same for unfolding and refolding. The first set of mutants tests the role of the α-helix in the transition state. Solvent-exposed residues Ala-6 and Gln-11 in the α-helix of native RNaseS were replaced by the helix destabilizing residues glycine or proline. A plot of log kon vs. log Kd for this series of mutants is linear over a very wide range, with a slope of −0.3, indicating that almost all of the molecules fold via a transition state involving the helix. A second set of mutants tests the role of side chains in the transition state. Three side chains were investigated: Phe-8, His-12, and Met-13, which are known to be important for binding S-peptide to S-protein and which also contribute strongly to the stability of RNaseS*. Only the side chain of Phe-8 contributes significantly, however, to the stability of the transition state. The results provide a remarkably clear description of a folding transition state. PMID:10051587

Sequentially distant but structurally similar proteins exhibit fold specific patterns based on their biophysical properties.

PubMed

Rajendran, Senthilnathan; Jothi, Arunachalam

2018-05-16

The Three-dimensional structure of a protein depends on the interaction between their amino acid residues. These interactions are in turn influenced by various biophysical properties of the amino acids. There are several examples of proteins that share the same fold but are very dissimilar at the sequence level. For proteins to share a common fold some crucial interactions should be maintained despite insignificant sequence similarity. Since the interactions are because of the biophysical properties of the amino acids, we should be able to detect descriptive patterns for folds at such a property level. In this line, the main focus of our research is to analyze such proteins and to characterize them in terms of their biophysical properties. Protein structures with sequence similarity lesser than 40% were selected for ten different subfolds from three different mainfolds (according to CATH classification) and were used for this analysis. We used the normalized values of the 49 physio-chemical, energetic and conformational properties of amino acids. We characterize the folds based on the average biophysical property values. We also observed a fold specific correlational behavior of biophysical properties despite a very low sequence similarity in our data. We further trained three different binary classification models (Naive Bayes-NB, Support Vector Machines-SVM and Bayesian Generalized Linear Model-BGLM) which could discriminate mainfold based on the biophysical properties. We also show that among the three generated models, the BGLM classifier model was able to discriminate protein sequences coming under all beta category with 81.43% accuracy and all alpha, alpha-beta proteins with 83.37% accuracy. Copyright © 2018 Elsevier Ltd. All rights reserved.

Nonparametric Model of Smooth Muscle Force Production During Electrical Stimulation.

PubMed

Cole, Marc; Eikenberry, Steffen; Kato, Takahide; Sandler, Roman A; Yamashiro, Stanley M; Marmarelis, Vasilis Z

2017-03-01

A nonparametric model of smooth muscle tension response to electrical stimulation was estimated using the Laguerre expansion technique of nonlinear system kernel estimation. The experimental data consisted of force responses of smooth muscle to energy-matched alternating single pulse and burst current stimuli. The burst stimuli led to at least a 10-fold increase in peak force in smooth muscle from Mytilus edulis, despite the constant energy constraint. A linear model did not fit the data. However, a second-order model fit the data accurately, so the higher-order models were not required to fit the data. Results showed that smooth muscle force response is not linearly related to the stimulation power.

Communication: nanosecond folding dynamics of an alpha helix: time-dependent 2D-IR cross peaks observed using polarization-sensitive dispersed pump-probe spectroscopy.

PubMed

Panman, Matthijs R; van Dijk, Chris N; Meuzelaar, Heleen; Woutersen, S

2015-01-28

We present a simple method to measure the dynamics of cross peaks in time-resolved two-dimensional vibrational spectroscopy. By combining suitably weighted dispersed pump-probe spectra, we eliminate the diagonal contribution to the 2D-IR response, so that the dispersed pump-probe signal contains the projection of only the cross peaks onto one of the axes of the 2D-IR spectrum. We apply the method to investigate the folding dynamics of an alpha-helical peptide in a temperature-jump experiment and find characteristic folding and unfolding time constants of 260 ± 30 and 580 ± 70 ns at 298 K.

In Vivo engineering of the vocal fold ECM with injectable HA hydrogels-late effects on tissue repair and biomechanics in a rabbit model.

PubMed

Thibeault, Susan L; Klemuk, Sarah A; Chen, Xia; Quinchia Johnson, Beatriz H

2011-03-01

To determine if the utilization of injectable chemically modified hyaluronan (HA) derivative at the time of intentional vocal fold resection may facilitate wound repair and preserve the unique viscoelastic properties of the extracellular matrix (ECM) and lamina propria 6 months after treatment. Prospective, controlled animal study. Twelve rabbit vocal folds were biopsied bilaterally, and the left side of vocal fold was treated with Extracel, an injectable, chemically modified HA derivative, and the right side of vocal fold was injected with saline as control at the time of resection. Animals were sacrificed 6 months after biopsy and injection. Outcomes measured include transcription levels for procollagen, fibronectin, fibromodulin, transforming growth factor beta one (TGF-β1), HA synthase, and hyaluronidase, and tissue biomechanics-viscosity and elasticity. Extracel-treated vocal folds were found to have significantly less fibrosis than saline-treated controls. Extracel-treated vocal folds had significantly improved biomechanical properties of elasticity and viscosity. Significantly decreased levels of fibronectin, fibromodulin, TGF-β1, procollagen I, and HA synthase were measured. Prophylactic in vivo manipulation of the ECM with an injectable HA hydrogel appears to induce vocal fold tissue regeneration to yield improved tissue composition and biomechanical properties at 6 months. Copyright © 2011 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

Linear summation of outputs in a balanced network model of motor cortex

PubMed Central

Capaday, Charles; van Vreeswijk, Carl

2015-01-01

Given the non-linearities of the neural circuitry's elements, we would expect cortical circuits to respond non-linearly when activated. Surprisingly, when two points in the motor cortex are activated simultaneously, the EMG responses are the linear sum of the responses evoked by each of the points activated separately. Additionally, the corticospinal transfer function is close to linear, implying that the synaptic interactions in motor cortex must be effectively linear. To account for this, here we develop a model of motor cortex composed of multiple interconnected points, each comprised of reciprocally connected excitatory and inhibitory neurons. We show how non-linearities in neuronal transfer functions are eschewed by strong synaptic interactions within each point. Consequently, the simultaneous activation of multiple points results in a linear summation of their respective outputs. We also consider the effects of reduction of inhibition at a cortical point when one or more surrounding points are active. The network response in this condition is linear over an approximately two- to three-fold decrease of inhibitory feedback strength. This result supports the idea that focal disinhibition allows linear coupling of motor cortical points to generate movement related muscle activation patterns; albeit with a limitation on gain control. The model also explains why neural activity does not spread as far out as the axonal connectivity allows, whilst also explaining why distant cortical points can be, nonetheless, functionally coupled by focal disinhibition. Finally, we discuss the advantages that linear interactions at the cortical level afford to motor command synthesis. PMID:26097452

Winnowing DNA for Rare Sequences: Highly Specific Sequence and Methylation Based Enrichment

PubMed Central

Thompson, Jason D.; Shibahara, Gosuke; Rajan, Sweta; Pel, Joel; Marziali, Andre

2012-01-01

Rare mutations in cell populations are known to be hallmarks of many diseases and cancers. Similarly, differential DNA methylation patterns arise in rare cell populations with diagnostic potential such as fetal cells circulating in maternal blood. Unfortunately, the frequency of alleles with diagnostic potential, relative to wild-type background sequence, is often well below the frequency of errors in currently available methods for sequence analysis, including very high throughput DNA sequencing. We demonstrate a DNA preparation and purification method that through non-linear electrophoretic separation in media containing oligonucleotide probes, achieves 10,000 fold enrichment of target DNA with single nucleotide specificity, and 100 fold enrichment of unmodified methylated DNA differing from the background by the methylation of a single cytosine residue. PMID:22355378

Linearization of the bradford protein assay.

PubMed

Ernst, Orna; Zor, Tsaffrir

2010-04-12

Determination of microgram quantities of protein in the Bradford Coomassie brilliant blue assay is accomplished by measurement of absorbance at 590 nm. This most common assay enables rapid and simple protein quantification in cell lysates, cellular fractions, or recombinant protein samples, for the purpose of normalization of biochemical measurements. However, an intrinsic nonlinearity compromises the sensitivity and accuracy of this method. It is shown that under standard assay conditions, the ratio of the absorbance measurements at 590 nm and 450 nm is strictly linear with protein concentration. This simple procedure increases the accuracy and improves the sensitivity of the assay about 10-fold, permitting quantification down to 50 ng of bovine serum albumin. Furthermore, the interference commonly introduced by detergents that are used to create the cell lysates is greatly reduced by the new protocol. A linear equation developed on the basis of mass action and Beer's law perfectly fits the experimental data.

Improving consensus contact prediction via server correlation reduction.

PubMed

Gao, Xin; Bu, Dongbo; Xu, Jinbo; Li, Ming

2009-05-06

Protein inter-residue contacts play a crucial role in the determination and prediction of protein structures. Previous studies on contact prediction indicate that although template-based consensus methods outperform sequence-based methods on targets with typical templates, such consensus methods perform poorly on new fold targets. However, we find out that even for new fold targets, the models generated by threading programs can contain many true contacts. The challenge is how to identify them. In this paper, we develop an integer linear programming model for consensus contact prediction. In contrast to the simple majority voting method assuming that all the individual servers are equally important and independent, the newly developed method evaluates their correlation by using maximum likelihood estimation and extracts independent latent servers from them by using principal component analysis. An integer linear programming method is then applied to assign a weight to each latent server to maximize the difference between true contacts and false ones. The proposed method is tested on the CASP7 data set. If the top L/5 predicted contacts are evaluated where L is the protein size, the average accuracy is 73%, which is much higher than that of any previously reported study. Moreover, if only the 15 new fold CASP7 targets are considered, our method achieves an average accuracy of 37%, which is much better than that of the majority voting method, SVM-LOMETS, SVM-SEQ, and SAM-T06. These methods demonstrate an average accuracy of 13.0%, 10.8%, 25.8% and 21.2%, respectively. Reducing server correlation and optimally combining independent latent servers show a significant improvement over the traditional consensus methods. This approach can hopefully provide a powerful tool for protein structure refinement and prediction use.

Lower capillary density but no difference in VEGF expression in obese vs. lean young skeletal muscle in humans.

PubMed

Gavin, Timothy P; Stallings, Howard W; Zwetsloot, Kevin A; Westerkamp, Lenna M; Ryan, Nicholas A; Moore, Rebecca A; Pofahl, Walter E; Hickner, Robert C

2005-01-01

Obesity is associated with lower skeletal muscle capillarization and lower insulin sensitivity. Vascular endothelial growth factor (VEGF) is important for the maintenance of the skeletal muscle capillaries. To investigate whether VEGF and VEGF receptor [kinase insert domain-containing receptor (KDR) and Flt-1] expression are lower with obesity, vastus lateralis muscle biopsies were obtained from eight obese and eight lean young sedentary men before and 2 h after a 1-h submaximal aerobic exercise bout for the measurement of VEGF, KDR, Flt-1, and skeletal muscle fiber and capillary characteristics. There were no differences in VEGF or VEGF receptor mRNA at rest between lean and obese muscle. Exercise increased VEGF (10-fold), KDR (3-fold), and Flt-1 (5-fold) mRNA independent of group. There were no differences in VEGF, KDR, or Flt-1 protein between groups. Compared with lean skeletal muscle, the number of capillary contacts per fiber was the same, but lower capillary density (CD), greater muscle cross sectional area, and lower capillary-to-fiber area ratio were observed in both type I and II fibers in obese muscle. Multiple linear regression revealed that 49% of the variance in insulin sensitivity (homeostasis model assessment) could be explained by percentage of body fat (35%) and maximal oxygen uptake per kilogram of fat-free mass (14%). Linear regression revealed significant relationships between maximal oxygen uptake and both CD and capillary-to-fiber perimeter exchange. Although differences may exist in CD and capillary-to-fiber area ratio between lean and obese skeletal muscle, the present results provide evidence that VEGF and VEGF receptor expression are not different between lean and obese muscle.

Limited Sampling Strategy for the Prediction of Area Under the Curve (AUC) of Statins: Reliability of a Single Time Point for AUC Prediction for Pravastatin and Simvastatin.

PubMed

Srinivas, N R

2016-02-01

Statins are widely prescribed medicines and are also available in fixed dose combinations with other drugs to treat several chronic ailments. Given the safety issues associated with statins it may be important to assess feasibility of a single time concentration strategy for prediction of exposure (area under the curve; AUC). The peak concentration (Cmax) was used to establish relationship with AUC separately for pravastatin and simvastatin using published pharmacokinetic data. The regression equations generated for statins were used to predict the AUC values from various literature references. The fold difference of the observed divided by predicted values along with correlation coefficient (r) were used to judge the feasibility of the single time point approach. Both pravastatin and simvastatin showed excellent correlation of Cmax vs. AUC values with r value ≥ 0.9638 (p<0.001). The fold difference was within 0.5-fold to 2-fold for 220 out of 227 AUC predictions and >81% of the predicted values were in a narrower range of >0.75-fold but <1.5-fold difference. Predicted vs. observed AUC values showed excellent correlation for pravastatin (r=0.9708, n=115; p<0.001) and simvastatin (r=0.9810; n=117; p<0.001) suggesting the utility of Cmax for AUC predictions. On the basis of the present work, it is feasible to develop a single concentration time point strategy that coincides with Cmax occurrence for both pravastatin and simvastatin from a therapeutic drug monitoring perspective. © Georg Thieme Verlag KG Stuttgart · New York.

Acute exposure to vibration is an apoptosis-inducing stimulus in the vocal fold epithelium.

PubMed

Novaleski, Carolyn K; Kimball, Emily E; Mizuta, Masanobu; Rousseau, Bernard

2016-10-01

Clinical voice disorders pose significant communication-related challenges to patients. The purpose of this study was to quantify the rate of apoptosis and tumor necrosis factor-alpha (TNF-α) signaling in vocal fold epithelial cells in response to increasing time-doses and cycle-doses of vibration. 20 New Zealand white breeder rabbits were randomized to three groups of time-doses of vibration exposure (30, 60, 120min) or a control group (120min of vocal fold adduction and abduction). Estimated cycle-doses of vocal fold vibration were extrapolated based on mean fundamental frequency. Laryngeal tissue specimens were evaluated for apoptosis and gene transcript and protein levels of TNF-α. Results revealed that terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was significantly higher after 120min of vibration compared to the control. Transmission electron microscopy (TEM) revealed no significant effect of time-dose on the mean area of epithelial cell nuclei. Extrapolated cycle-doses of vibration exposure were closely related to experimental time-dose conditions, although no significant correlations were observed with TUNEL staining or mean area of epithelial cell nuclei. TUNEL staining was positively correlated with TNF-α protein expression. Our findings suggest that apoptosis can be induced in the vocal fold epithelium after 120min of modal intensity phonation. In contrast, shorter durations of vibration exposure do not result in apoptosis signaling. However, morphological features of apoptosis are not observed using TEM. Future studies are necessary to examine the contribution of abnormal apoptosis to vocal fold diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

Acute Exposure to Vibration is an Apoptosis-Inducing Stimulus in the Vocal Fold Epithelium

PubMed Central

Novaleski, Carolyn K.; Kimball, Emily E.; Mizuta, Masanobu; Rousseau, Bernard

2016-01-01

Clinical voice disorders pose significant communication-related challenges to patients. The purpose of this study was to quantify the rate of apoptosis and tumor necrosis factor-alpha (TNF-α) signaling in vocal fold epithelial cells in response to increasing time-doses and cycle-doses of vibration. 20 New Zealand white breeder rabbits were randomized to three groups of time-doses of vibration exposure (30, 60, 120 minutes) or a control group (120 minutes of vocal fold adduction and abduction). Estimated cycle-doses of vocal fold vibration were extrapolated based on mean fundamental frequency. Laryngeal tissue specimens were evaluated for apoptosis and gene transcript and protein levels of TNF-α. Results revealed that terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was significantly higher after 120 minutes of vibration compared to the control. Transmission electron microscopy (TEM) revealed no significant effect of time-dose on the mean area of epithelial cell nuclei. Extrapolated cycle-doses of vibration exposure were closely related to experimental time-dose conditions, although no significant correlations were observed with TUNEL staining or mean area of epithelial cell nuclei. TUNEL staining was positively correlated with TNF-α protein expression. Our findings suggest that apoptosis can be induced in the vocal fold epithelium after 120 minutes of modal intensity phonation. In contrast, shorter durations of vibration exposure do not result in apoptosis signaling. However, morphological features of apoptosis are not observed using TEM. Future studies are necessary to examine the contribution of abnormal apoptosis to vocal fold diseases. PMID:27577014

Revealing the distinct folding phases of an RNA three-helix junction.

PubMed

Plumridge, Alex; Katz, Andrea M; Calvey, George D; Elber, Ron; Kirmizialtin, Serdal; Pollack, Lois

2018-05-14

Remarkable new insight has emerged into the biological role of RNA in cells. RNA folding and dynamics enable many of these newly discovered functions, calling for an understanding of RNA self-assembly and conformational dynamics. Because RNAs pass through multiple structures as they fold, an ensemble perspective is required to visualize the flow through fleetingly populated sets of states. Here, we combine microfluidic mixing technology and small angle X-ray scattering (SAXS) to measure the Mg-induced folding of a small RNA domain, the tP5abc three helix junction. Our measurements are interpreted using ensemble optimization to select atomically detailed structures that recapitulate each experimental curve. Structural ensembles, derived at key stages in both time-resolved studies and equilibrium titrations, reproduce the features of known intermediates, and more importantly, offer a powerful new structural perspective on the time-progression of folding. Distinct collapse phases along the pathway appear to be orchestrated by specific interactions with Mg ions. These key interactions subsequently direct motions of the backbone that position the partners of tertiary contacts for later bonding, and demonstrate a remarkable synergy between Mg and RNA across numerous time-scales.

Mid-Late Miocene deformation of the northern Kuqa fold-and-thrust belt (southern Chinese Tian Shan): An apatite (U-Th-Sm)/He study

NASA Astrophysics Data System (ADS)

Chang, Jian; Tian, Yuntao; Qiu, Nansheng

2017-01-01

The Kuqa fold-and-thrust belt developed in response to Cenozoic southward shortening between the Chinese Tian Shan and the Tarim Basin. This study aims to constrain the timing of the Late Cenozoic deformation by determining the onset time of enhanced rock cooling using apatite (U-Th-Sm)/He thermochronometry. Eight sedimentary samples were collected from Triassic to Cretaceous strata exposed along a 17 km N-S transect, cross-cutting the northern Kuqa fold-and-thrust belt. Single-grain AHe ages from these samples mostly cluster around 8-16 Ma and are younger than their depositional ages. Older AHe ages show a positive relationship with [eU], a proxy for radiation damage. Modelling of the observed age-eU relationships suggest a phase of enhanced cooling and erosion initiated at Mid-Late Miocene time (10-20 Ma) in the northern Kuqa fold-and-thrust belt. This result is consistent with a coeval abrupt increase of sedimentation rate in the foreland Kuqa depression, south of the study area, indicating a Mid-Late Miocene phase of shortening in the northern Kuqa fold-and-thrust belt.

Assessment of canine vocal fold function after injection of a new biomaterial designed to treat phonatory mucosal scarring.

PubMed

Karajanagi, Sandeep S; Lopez-Guerra, Gerardo; Park, Hyoungshin; Kobler, James B; Galindo, Marilyn; Aanestad, Jon; Mehta, Daryush D; Kumai, Yoshihiko; Giordano, Nicholas; d'Almeida, Anthony; Heaton, James T; Langer, Robert; Herrera, Victoria L M; Faquin, William; Hillman, Robert E; Zeitels, Steven M

2011-03-01

Most cases of irresolvable hoarseness are due to deficiencies in the pliability and volume of the superficial lamina propria of the phonatory mucosa. By using a US Food and Drug Administration-approved polymer, polyethylene glycol (PEG), we created a novel hydrogel (PEG30) and investigated its effects on multiple vocal fold structural and functional parameters. We injected PEG30 unilaterally into 16 normal canine vocal folds with survival times of 1 to 4 months. High-speed videos of vocal fold vibration, induced by intratracheal airflow, and phonation threshold pressures were recorded at 4 time points per subject. Three-dimensional reconstruction analysis of 11.7 T magnetic resonance images and histologic analysis identified 3 cases wherein PEG30 injections were the most superficial, so as to maximally impact vibratory function. These cases were subjected to in-depth analyses. High-speed video analysis of the 3 selected cases showed minimal to no reduction in the maximum vibratory amplitudes of vocal folds injected with PEG30 compared to the non-injected, contralateral vocal fold. All PEG30-injected vocal folds displayed mucosal wave activity with low average phonation threshold pressures. No significant inflammation was observed on microlaryngoscopic examination. Magnetic resonance imaging and histologic analyses revealed time-dependent resorption of the PEG30 hydrogel by phagocytosis with minimal tissue reaction or fibrosis. The PEG30 hydrogel is a promising biocompatible candidate biomaterial to restore form and function to deficient phonatory mucosa, while not mechanically impeding residual endogenous superficial lamina propria.

Measurement and modeling of intrinsic transcription terminators

PubMed Central

Cambray, Guillaume; Guimaraes, Joao C.; Mutalik, Vivek K.; Lam, Colin; Mai, Quynh-Anh; Thimmaiah, Tim; Carothers, James M.; Arkin, Adam P.; Endy, Drew

2013-01-01

The reliable forward engineering of genetic systems remains limited by the ad hoc reuse of many types of basic genetic elements. Although a few intrinsic prokaryotic transcription terminators are used routinely, termination efficiencies have not been studied systematically. Here, we developed and validated a genetic architecture that enables reliable measurement of termination efficiencies. We then assembled a collection of 61 natural and synthetic terminators that collectively encode termination efficiencies across an ∼800-fold dynamic range within Escherichia coli. We simulated co-transcriptional RNA folding dynamics to identify competing secondary structures that might interfere with terminator folding kinetics or impact termination activity. We found that structures extending beyond the core terminator stem are likely to increase terminator activity. By excluding terminators encoding such context-confounding elements, we were able to develop a linear sequence-function model that can be used to estimate termination efficiencies (r = 0.9, n = 31) better than models trained on all terminators (r = 0.67, n = 54). The resulting systematically measured collection of terminators should improve the engineering of synthetic genetic systems and also advance quantitative modeling of transcription termination. PMID:23511967

Quantitative analysis and prediction of G-quadruplex forming sequences in double-stranded DNA

PubMed Central

Kim, Minji; Kreig, Alex; Lee, Chun-Ying; Rube, H. Tomas; Calvert, Jacob; Song, Jun S.; Myong, Sua

2016-01-01

Abstract G-quadruplex (GQ) is a four-stranded DNA structure that can be formed in guanine-rich sequences. GQ structures have been proposed to regulate diverse biological processes including transcription, replication, translation and telomere maintenance. Recent studies have demonstrated the existence of GQ DNA in live mammalian cells and a significant number of potential GQ forming sequences in the human genome. We present a systematic and quantitative analysis of GQ folding propensity on a large set of 438 GQ forming sequences in double-stranded DNA by integrating fluorescence measurement, single-molecule imaging and computational modeling. We find that short minimum loop length and the thymine base are two main factors that lead to high GQ folding propensity. Linear and Gaussian process regression models further validate that the GQ folding potential can be predicted with high accuracy based on the loop length distribution and the nucleotide content of the loop sequences. Our study provides important new parameters that can inform the evaluation and classification of putative GQ sequences in the human genome. PMID:27095201

ortho- and meta-substituted aromatic thiols are efficient redox buffers that increase the folding rate of a disulfide-containing protein.

PubMed

Gough, Jonathan D; Barrett, Elvis J; Silva, Yenia; Lees, Watson J

2006-08-20

Thiol based redox buffers are used to enhance the folding rates of disulfide-containing proteins in vitro. Traditionally, small molecule aliphatic thiols such as glutathione are employed. Recently, we have demonstrated that aromatic thiols can further enhance protein-folding rates. In the presence of para-substituted aromatic thiols the folding rate of a disulfide-containing protein was increased by 4-23 times over that measured for glutathione. However, several important practical issues remain to be addressed. Aromatic thiols have never been tested in the presence of denaturants such as guanidine hydrochloride. Only two of the para-substituted aromatic thiols previously examined are commercially available. To expand the number of aromatic thiols for protein folding, several commercially available meta- and ortho-substituted aromatic thiols were studied. Furthermore, an ortho-substituted aromatic thiol, easily obtained from inexpensive starting materials, was investigated. Folding rates of scrambled ribonuclease A at pH 6.0, 7.0 and 7.7, with ortho- and meta-substituted aromatic thiols, were up to 10 times greater than those with glutathione. In the presence of the common denaturant guanidine hydrochloride (0.5M) aromatic thiols provided 100% yield of active protein while maintaining equivalent folding rates.

Non-Targeted Effects Models Predict Significantly Higher Mars Mission Cancer Risk than Targeted Effects Models

DOE PAGES

Cucinotta, Francis A.; Cacao, Eliedonna

2017-05-12

Cancer risk is an important concern for galactic cosmic ray (GCR) exposures, which consist of a wide-energy range of protons, heavy ions and secondary radiation produced in shielding and tissues. Relative biological effectiveness (RBE) factors for surrogate cancer endpoints in cell culture models and tumor induction in mice vary considerable, including significant variations for different tissues and mouse strains. Many studies suggest non-targeted effects (NTE) occur for low doses of high linear energy transfer (LET) radiation, leading to deviation from the linear dose response model used in radiation protection. Using the mouse Harderian gland tumor experiment, the only extensive data-setmore » for dose response modelling with a variety of particle types (>4), for the first-time a particle track structure model of tumor prevalence is used to investigate the effects of NTEs in predictions of chronic GCR exposure risk. The NTE model led to a predicted risk 2-fold higher compared to a targeted effects model. The scarcity of data with animal models for tissues that dominate human radiation cancer risk, including lung, colon, breast, liver, and stomach, suggest that studies of NTEs in other tissues are urgently needed prior to long-term space missions outside the protection of the Earth’s geomagnetic sphere.« less

Detection of pseudorabies virus by duplex droplet digital PCR assay.

PubMed

Ren, Meishen; Lin, Hua; Chen, Shijie; Yang, Miao; An, Wei; Wang, Yin; Xue, Changhua; Sun, Yinjie; Yan, Yubao; Hu, Juan

2018-01-01

Aujeszky's disease, caused by pseudorabies virus (PRV), has damaged the economy of the Chinese swine industry. A large number of PRV gene-deleted vaccines have been constructed based on deletion of the glycoprotein E ( gE) gene combined with other virulence-related gene deletions, such as thymidine kinase ( TK), whereas PRV wild-type strains contain an intact gE gene. We developed a sensitive duplex droplet digital PCR (ddPCR) assay to rapidly detect PRV wild-type isolates and gE gene-deleted viral vaccines. We compared this assay with a TaqMan real-time PCR (qPCR) using the same primers and probes. Both assays exhibited good linearity and repeatability; however, ddPCR maintained linearity at extremely low concentrations, whereas qPCR did not. Based on positive results for both gE and gB, the detection limit of ddPCR was found to be 4.75 copies/µL in contrast of 76 copies/µL for qPCR, showing that ddPCR provided a 16-fold improvement in sensitivity. In addition, no nonspecific amplification was shown in specificity testing, and the PRV wild-type was distinguished from a gE-deleted strain. The ddPCR was more sensitive when analyzing clinical serum samples. Thus, ddPCR may become an appropriate detection platform for PRV.

Effects of 18beta-glycyrrhetinic acid on the junctional complex and steroidogenesis in rat adrenocortical cells.

PubMed

Huang, Shih-Horng; Wu, Jiahn-Chun; Hwang, Ra-Der; Yeo, Hui-Lin; Wang, Seu-Mei

2003-09-01

Cellular junctions play important roles in cell differentiation, signal transduction, and cell function. This study investigated their function in steroid secretion by adrenal cells. Immunofluorescence staining revealed the presence of gap junctions and adherens junctions between adrenal cells. The major gap junction protein, connexin43, was seen as a linear dotted pattern of the typical gap junction plaques, in contrast to alpha-, beta-, and gamma-catenin, which were seen as continuous, linear staining of cell-cell adherens junction. Treatment with 18beta-glycyrrhetinic acid, a gap junction inhibitor, reduced the immunoreactivity of these proteins in a time- and dose-dependent manner, and caused the gap junction and adherens junction to separate longitudinally from the cell-cell contact sites, indicating the structural interdependency of these two junctions. Interestingly, 18beta-glycyrrhetinic acid stimulated a two- to three-fold increase in steroid production in these adrenal cells lacking intact cell junctions. These data raise the question of the necessity for cell communication for the endocrine function of adrenal cells. Pharmacological analyses indicated that the steroidogenic effect of 18beta-glycyrrhetinic acid was partially mediated by extracellular signal-related kinase and calcium/calmodulin-dependent kinase, a pathway distinct from the protein kinase A signaling pathway already known to mediate steroidogenesis in adrenal cells. Copyright 2003 Wiley-Liss, Inc.

Non-Targeted Effects Models Predict Significantly Higher Mars Mission Cancer Risk than Targeted Effects Models

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

Cucinotta, Francis A.; Cacao, Eliedonna

Cancer risk is an important concern for galactic cosmic ray (GCR) exposures, which consist of a wide-energy range of protons, heavy ions and secondary radiation produced in shielding and tissues. Relative biological effectiveness (RBE) factors for surrogate cancer endpoints in cell culture models and tumor induction in mice vary considerable, including significant variations for different tissues and mouse strains. Many studies suggest non-targeted effects (NTE) occur for low doses of high linear energy transfer (LET) radiation, leading to deviation from the linear dose response model used in radiation protection. Using the mouse Harderian gland tumor experiment, the only extensive data-setmore » for dose response modelling with a variety of particle types (>4), for the first-time a particle track structure model of tumor prevalence is used to investigate the effects of NTEs in predictions of chronic GCR exposure risk. The NTE model led to a predicted risk 2-fold higher compared to a targeted effects model. The scarcity of data with animal models for tissues that dominate human radiation cancer risk, including lung, colon, breast, liver, and stomach, suggest that studies of NTEs in other tissues are urgently needed prior to long-term space missions outside the protection of the Earth’s geomagnetic sphere.« less

Ionizing radiation induces O6-alkylguanine-DNA-alkyltransferase mRNA and activity in mouse tissues.

PubMed

Wilson, R E; Hoey, B; Margison, G P

1993-04-01

The effect of exposure to whole-body gamma-irradiation or fast electrons on O6-alkylguanine-DNA-alkyltransferase (ATase) activity and mRNA abundance has been examined in mice. In response to gamma-radiation, hepatic ATase activity was significantly raised in BDF1 mice 24 h post-irradiation, reaching a maximum of 2- to 3-fold at 36 h and beginning to decrease by 48-60 h. A small but consistently higher level of induction was achieved when mice were exposed using a low dose rate (0.015 Gy/min) compared to a high dose rate (0.5 Gy/min). ATase activity was also induced approximately 2-fold 48 h post-irradiation in brain, kidney, lung and spleen, with a greater induction again observed in response to the lower dose rate. In response to fast electrons from a linear accelerator hepatic ATase activity was also induced 2- to 3-fold 48 h post-irradiation in BDF1, BALB/c, C57Bl and DBA2 strains. Induction of ATase activity in livers of BDF1 mice was observed 48 h after a total single dose of 5 Gy gamma-radiation (2-fold), increasing to a slightly higher level at 15 Gy, but no induction was observed at doses of 2 Gy and below. Although a maximum 2- to 3-fold induction of ATase activity was observed, mRNA levels were induced 3- to 4-fold by 48 h after a dose of 15 Gy. Furthermore, significant increases in mRNA levels were detected at low doses (1-2 Gy) at which there was no apparent increase in ATase activity. This suggests that ionizing radiation increases ATase levels by a process involving transcriptional upregulation but that strong post-transcriptional and/or translational controls operate to limit induction of enzyme activity to 2- to 3-fold. This is the first report of an in vivo induction of ATase by ionizing radiation in a species other than the rat.

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

Ilieva, N., E-mail: nevena.ilieva@parallel.bas.bg; Dai, J., E-mail: daijing491@gmail.com; Sieradzan, A., E-mail: adams86@wp.pl

Protein folding [1] is the process of formation of a functional 3D structure from a random coil — the shape in which amino-acid chains leave the ribosome. Anfinsen’s dogma states that the native 3D shape of a protein is completely determined by protein’s amino acid sequence. Despite the progress in understanding the process rate and the success in folding prediction for some small proteins, with presently available physics-based methods it is not yet possible to reliably deduce the shape of a biologically active protein from its amino acid sequence. The protein-folding problem endures as one of the most important unresolvedmore » problems in science; it addresses the origin of life itself. Furthermore, a wrong fold is a common cause for a protein to lose its function or even endanger the living organism. Soliton solutions of a generalized discrete non-linear Schrödinger equation (GDNLSE) obtained from the energy function in terms of bond and torsion angles κ and τ provide a constructive theoretical framework for describing protein folds and folding patterns [2]. Here we study the dynamics of this process by means of molecular-dynamics simulations. The soliton manifestation is the pattern helix–loop–helix in the secondary structure of the protein, which explains the importance of understanding loop formation in helical proteins. We performed in silico experiments for unfolding one subunit of the core structure of gp41 from the HIV envelope glycoprotein (PDB ID: 1AIK [3]) by molecular-dynamics simulations with the MD package GROMACS. We analyzed 80 ns trajectories, obtained with one united-atom and two different all-atom force fields, to justify the side-chain orientation quantification scheme adopted in the studies and to eliminate force-field based artifacts. Our results are compatible with the soliton model of protein folding and provide first insight into soliton-formation dynamics.« less

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.

Development of a sufficient and effective procedure for transformation of an oleaginous yeast, Rhodosporidium toruloides DMKU3-TK16.

PubMed

Tsai, Yung-Yu; Ohashi, Takao; Kanazawa, Takenori; Polburee, Pirapan; Misaki, Ryo; Limtong, Savitree; Fujiyama, Kazuhito

2017-05-01

Rhodosporidium toruloides DMKU3-TK16 (TK16), a basidiomycetous yeast isolated in Thailand, can produce a large amount of oil corresponding to approximately 70 % of its dry cell weight. However, lack of a sufficient and efficient transformation method makes further genetic manipulation of this organism difficult. We here developed a new transformation system for R. toruloides using a lithium acetate method with the Sh ble gene as a selective marker under the control of the R. toruloides ATCC 10657 GPD1 promoter. A linear DNA fragment containing the Sh ble gene expression cassette was integrated into the genome, and its integration was confirmed by colony PCR and Southern blot. Then, we further optimized the parameters affecting the transformation efficiency, such as the amount of linear DNA, the growth phase, the incubation time in the transformation mixture, the heat shock treatment temperature, the addition of DMSO and carrier DNA, and the recovery incubation time. With the developed method, the transformation efficiency of approximately 25 transformants/μg DNA was achieved. Compared with the initial trial, transformation efficiency was enhanced 417-fold. We further demonstrated the heterologous production of EGFP in TK16 by microscopic observation and immunoblot analysis, and use the technique to disrupt the endogenous URA3 gene. The newly developed method is thus simple and time saving, making it useful for efficient introduction of an exogenous gene into R. toruloides strains. Accordingly, this new practical approach should facilitate the molecular manipulation, such as target gene introduction and deletion, of TK16 and other R. toruloides strains as a major source of biodiesel.

Automated measurement of cattle surface temperature and its correlation with rectal temperature

PubMed Central

Ren, Kang; Chen, XiaoLi; Lu, YongQiang; Wang, Dong

2017-01-01

The body temperature of cattle varies regularly with both the reproductive cycle and disease status. Establishing an automatic method for monitoring body temperature may facilitate better management of reproduction and disease control in cattle. Here, we developed an Automatic Measurement System for Cattle’s Surface Temperature (AMSCST) to measure the temperature of metatarsus by attaching a special shell designed to fit the anatomy of cattle’s hind leg. Using AMSCST, the surface temperature (ST) on the metatarsus of the hind leg was successively measured during 24 hours a day with an interval of one hour in three tested seasons. Based on ST and rectal temperature (RT) detected by AMSCST and mercury thermometer, respectively, a linear mixed model was established, regarding both the time point and seasonal factors as the fixed effects. Unary linear correlation and Bland-Altman analysis results indicated that the temperatures measured by AMSCST were closely correlated to those measured by mercury thermometer (R2 = 0.998), suggesting that the AMSCST is an accurate and reliable way to detect cattle’s body temperature. Statistical analysis showed that the differences of STs among the three seasons, or among the different time points were significant (P<0.05), and the differences of RTs among the different time points were similarly significant (P<0.05). The prediction accuracy of the mixed model was verified by 10-fold cross validation. The average difference between measured RT and predicted RT was about 0.10 ± 0.10°C with the association coefficient of 0.644, indicating the feasibility of this model in measuring cattle body temperature. Therefore, an automated technology for accurately measuring cattle body temperature was accomplished by inventing an optimal device and establishing the AMSCST system. PMID:28426682

Empirical study of the dependence of the results of multivariable flexible survival analyses on model selection strategy.

PubMed

Binquet, C; Abrahamowicz, M; Mahboubi, A; Jooste, V; Faivre, J; Bonithon-Kopp, C; Quantin, C

2008-12-30

Flexible survival models, which avoid assumptions about hazards proportionality (PH) or linearity of continuous covariates effects, bring the issues of model selection to a new level of complexity. Each 'candidate covariate' requires inter-dependent decisions regarding (i) its inclusion in the model, and representation of its effects on the log hazard as (ii) either constant over time or time-dependent (TD) and, for continuous covariates, (iii) either loglinear or non-loglinear (NL). Moreover, 'optimal' decisions for one covariate depend on the decisions regarding others. Thus, some efficient model-building strategy is necessary.We carried out an empirical study of the impact of the model selection strategy on the estimates obtained in flexible multivariable survival analyses of prognostic factors for mortality in 273 gastric cancer patients. We used 10 different strategies to select alternative multivariable parametric as well as spline-based models, allowing flexible modeling of non-parametric (TD and/or NL) effects. We employed 5-fold cross-validation to compare the predictive ability of alternative models.All flexible models indicated significant non-linearity and changes over time in the effect of age at diagnosis. Conventional 'parametric' models suggested the lack of period effect, whereas more flexible strategies indicated a significant NL effect. Cross-validation confirmed that flexible models predicted better mortality. The resulting differences in the 'final model' selected by various strategies had also impact on the risk prediction for individual subjects.Overall, our analyses underline (a) the importance of accounting for significant non-parametric effects of covariates and (b) the need for developing accurate model selection strategies for flexible survival analyses. Copyright 2008 John Wiley & Sons, Ltd.

Development and application of stir bar sorptive extraction with polyurethane foams for the determination of testosterone and methenolone in urine matrices.

PubMed

Sequeiros, R C P; Neng, N R; Portugal, F C M; Pinto, M L; Pires, J; Nogueira, J M F

2011-04-01

This work describes the development, validation, and application of a novel methodology for the determination of testosterone and methenolone in urine matrices by stir bar sorptive extraction using polyurethane foams [SBSE(PU)] followed by liquid desorption and high-performance liquid chromatography with diode array detection. The methodology was optimized in terms of extraction time, agitation speed, pH, ionic strength and organic modifier, as well as back-extraction solvent and desorption time. Under optimized experimental conditions, convenient accuracy were achieved with average recoveries of 49.7 8.6% for testosterone and 54.2 ± 4.7% for methenolone. Additionally, the methodology showed good precision (<9%), excellent linear dynamic ranges (>0.9963) and convenient detection limits (0.2-0.3 μg/L). When comparing the efficiency obtained by SBSE(PU) and with the conventional polydimethylsiloxane phase [SBSE(PDMS)], yields up to four-fold higher are attained for the former, under the same experimental conditions. The application of the proposed methodology for the analysis of testosterone and methenolone in urine matrices showed negligible matrix effects and good analytical performance.

Cytotoxic and mutagenic properties of shale oil byproducts. II. Comparison of mutagenic effects at five genetic markers induced by retort process water plus near ultraviolet light in Chinese hamster ovary cells

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

Chen, D.J.C.; Strniste, G.F.

1982-01-01

A Chinese hamster ovary (CHO) cell line heterozygous at the adenine phosphoribosyl transferase (APRT) locus was used for selection of induced mutants resistant to 8-azaadenine (8AA), 6-thioguanine (6TG), ouabain (OUA), emetine (EMT) and diphtheria toxin (DIP). The expression times necessary for optimizing the number of mutants recovered at the different loci have been determined using the known direct acting mutagen, far ultraviolet light (FUV), and a complex aqueous organic mixture (shale oil process water) activated with near ultraviolet light (NUV). The results indicate that optimal expression times following treatment with either mutagen was between 2 and 8 days. For CHOmore » cells treated with shale oil process water and subsequently exposed to NUV a linear dose response for mutant induction was observed for all five genetic loci. At 10% surviving fraction of cells, between 35- and 130-fold increases above backgound mutation frequencies were observed for the various markers examined.« less

Growth of Fault-Cored Anticlines by Flexural Slip Folding: Analysis by Boundary Element Modeling

NASA Astrophysics Data System (ADS)

Johnson, Kaj M.

2018-03-01

Fault-related folds develop due to a combination of slip on the associated fault and distributed deformation off the fault. Under conditions that are sufficient for sedimentary layering to act as a stack of mechanical layers with contact slip, buckling can dramatically amplify the folding process. We develop boundary element models of fault-related folding of viscoelastic layers embedded with a reverse fault to examine the influence of such layering on fold growth. The strength of bedding contacts, the thickness and stiffness of layering, and fault geometry all contribute significantly to the resulting fold form. Frictional contact strength between layers controls the degree of localization of slip within fold limbs; high contact friction in relatively thin bedding tends to localize bedding slip within narrow kink bands on fold limbs, and low contact friction tends to produce widespread bedding slip and concentric fold form. Straight ramp faults tend to produce symmetric folds, whereas listric faults tend to produce asymmetric folds with short forelimbs and longer backlimbs. Fault-related buckle folds grow exponentially with time under steady loading rates. At early stages of folding, fold growth is largely attributed to slip on the fault, but as the fold increases amplitude, a larger portion of the fold growth is attributed to distributed slip across bedding contacts on the limbs of the fold. An important implication for geologic and earthquake studies is that not all surface deformation associated with blind reverse faults may be attributed to slip on the fault during earthquakes.

Variability of normal vocal fold dynamics for different vocal loading in one healthy subject investigated by phonovibrograms.

PubMed

Doellinger, Michael; Lohscheller, Joerg; McWhorter, Andrew; Kunduk, Melda

2009-03-01

We investigate the potential of high-speed digital imaging technique (HSI) and the phonovibrogram (PVG) analysis in normal vocal fold dynamics by studying the effects of continuous voice use (vocal loading) during the workday. One healthy subject was recorded at sustained phonation 13 times within 2 consecutive days in the morning before and in the afternoon after vocal loading, respectively. Vocal fold dynamics were extracted and visualized by PVGs. The characteristic PVG patterns were extracted representing vocal fold vibration types. The parameter values were then analyzed by statistics regarding vocal load, left-right PVG asymmetries, anterior-posterior PVG asymmetries, and opening-closing differences. For the first time, the direct impact of vocal load could be determined by analyzing vocal fold dynamics. For same vocal loading conditions, equal dynamical behavior of the vocal folds were confirmed. Comparison of recordings performed in the morning with the recordings after work revealed significant changes in vibration behavior, indicating impact of occurring vocal load. Left-right asymmetries in vocal fold dynamics were found confirming earlier assumptions. Different dynamics between opening and closing procedure as well as for anterior and posterior parts were found. Constant voice usage stresses the vocal folds even in healthy subjects and can be detected by applying the PVG technique. Furthermore, left-right PVG asymmetries do occur in healthy voice to a certain extent. HSI in combination with PVG analysis seems to be a promising tool for investigation of vocal fold fatigue and pathologies resulting in small forms of dynamical changes.

Sample stacking of fast-moving anions in capillary zone electrophoresis with pH-suppressed electroosmotic flow.

PubMed

Quirino, J P; Terabe, S

1999-07-30

On-line sample concentration of fast moving inorganic anions by large volume sample stacking (LVSS) and field enhanced sample injection (FESI) with a water plug under acidic conditions is presented. Detection sensitivity enhancements were around 100 and 1000-fold for LVSS and FESI, respectively. However, reproducibility and linearity of response in the LVSS approach is superior compared to the FESI approach.

Conceptual MEMS Devices for a Redeployable Antenna

DTIC Science & Technology

2007-09-01

micromirrors in projection devices, and various sensors for chemical/biological applications. MEMS are a key aspect of ever- increasing significance in...with a vertical thermal actuator, linear assembly micromotor, and a locking mechanism, to create a scanning micromirror and cube reflector system. The... Micromirrors ,” Transducers, pp347-350, 1997. [24] Shimoyama, I., O. Kano, and H. Miura. “3D Microstructures Folded by Lorentz Force,” 11th

Characteristics of the fourth order resonance in high intensity linear accelerators

NASA Astrophysics Data System (ADS)

Jeon, D.; Hwang, Kyung Ryun

2017-06-01

For the 4σ = 360° space-charge resonance in high intensity linear accelerators, the emittance growth is surveyed for input Gaussian beams, as a function of the depressed phase advance per cell σ and the initial tune depression (σo - σ). For each data point, the linac lattice is designed such that the fourth order resonance dominates over the envelope instability. The data show that the maximum emittance growth takes place at σ ≈ 87° over a wide range of the tune depression (or beam current), which confirms that the relevant parameter for the emittance growth is σ and that for the bandwidth is σo - σ. An interesting four-fold phase space structure is observed that cannot be explained with the fourth order resonance terms alone. Analysis attributes this effect to a small negative sixth order detuning term as the beam is redistributed by the resonance. Analytical studies show that the tune increases monotonically for the Gaussian beam which prevents the resonance for σ > 90°. Frequency analysis indicates that the four-fold structure observed for input Kapchinskij-Vladmirskij beams when σ < 90°, is not the fourth order resonance but a fourth order envelope instability because the 1/4 = 90°/360° component is missing in the frequency spectrum.

Development of electrochemical folic acid sensor based on hydroxyapatite nanoparticles.

PubMed

Kanchana, P; Sekar, C

2015-02-25

We report the synthesis of hydroxyapatite (HA) nanoparticles (NPs) by a simple microwave irradiation method and its application as sensing element for the precise determination of folic acid (FA) by electrochemical method. The structure and composition of the HA NPs characterized using XRD, FTIR, Raman and XPS. SEM and EDX studies confirmed the formation of elongated spherical shaped HA NPs with an average particle size of about 34 nm. The HA NPs thin film on glassy carbon electrode (GCE) were deposited by drop casting method. Electrocatalytic behavior of FA in the physiological pH 7.0 was investigated by cyclic voltammetry (CV), linear sweep voltammetry (LSV) and chronoamperometry. The fabricated HA/GCE exhibited a linear calibration plot over a wide FA concentration ranging from 1.0×10(-7) to 3.5×10(-4) M with the detection limit of 75 nM. In addition, the HA NPs modified GCE showed good selectivity toward the determination of FA even in the presence of a 100-fold excess of ascorbic acid (AA) and 1000-fold excess of other common interferents. The fabricated biosensor exhibits good sensitivity and stability, and was successfully applied for the determination of FA in pharmaceutical samples. Copyright © 2014 Elsevier B.V. All rights reserved.

Preparation of a Strong Gelatin-Short Linear Glucan Nanocomposite Hydrogel by an in Situ Self-Assembly Process.

PubMed

Ge, Shengju; Li, Man; Ji, Na; Liu, Jing; Mul, Hongyan; Xiong, Liu; Sun, Qingjie

2018-01-10

Gelatin hydrogels exhibit excellent biocompatibility, nonimmunogenicity, and biodegradability, but they have limited applications in the food and medical industries because of their poor mechanical properties. Herein, we first developed an in situ self-assembly process for the preparation of gelatin-short linear glucan (SLG) nanocomposite hydrogels with enhanced mechanical strength. The microstructure, dynamic viscoelasticity, compression behavior, and thermal characteristics of the gelatin-SLG nanocomposite hydrogels were determined using scanning electron microscopy (SEM), dynamic rheological experiments, compression tests, and texture profile analysis tests. The SEM images revealed that nanoparticles were formed by the in situ self-assembly of SLG in the gelatin matrix and that the size of these nanoparticles ranged between 200 and 600 nm. The pores of the nanocomposite hydrogels were smaller than those of the pure gelatin hydrogels. Transmission electron microscopy images and X-ray diffraction further confirmed the presence of SLG nanoparticles with spherical shapes and B-type structures. Compared with pure gelatin hydrogels, the nanocomposite hydrogels exhibited improved mechanical behavior. Notably, the hardness and maximum values of the compressive stress of gelatin-SLG nanocomposites containing 5% SLG increased by about 2-fold and 3-fold, respectively, compared to the corresponding values of pure gelatin hydrogels.

Stability of a family of uniform vortices related to vortex configurations before merging

NASA Astrophysics Data System (ADS)

Luzzatto-Fegiz, P.; Williamson, C. H. K.

2006-11-01

Motivated by the merger of two corotating vortices, Cerretelli & Williamson (JFM 2003) discovered a family of uniform vorticity patches representing the continuation of two corotating vortices into a single ``dumbbell'' shape. This branch of solutions passes through a bifurcation from the Kirchhoff ellipses (discovered by Kamm 1987 and Saffman 1988) and ends into a cat's eye shape. By using a more accurate method for equilibrium shape calculation, we find some differences in the equilibrium shapes to those discovered by Cerretelli & Williamson, particularly near the topological change (from a two-vortex to a single vortex shape). We implement the approach of Dritschel (1985), and show that all the simply connected shapes are unstable to a three-fold perturbation, while a regime of the two-vortex shapes nearing the topological change is unstable to a two-fold antisymmetric perturbation. The stability of two patches has been source of debate in the literature. Saffman & Szeto (1980) predicted exchange of stability at an extremum in energy and angular momentum; on the other hand, Dritschel (1985) found that conditions for instability from linear analysis did not match those coming from the energy criterion. In the present work, we find precise agreement between results from linear analysis and energy criterion, in accordance with the more recent work of Kamm (1987) and Dritschel (1995).

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

Co-immobilization of glucose oxidase and xylose dehydrogenase displayed whole cell on multiwalled carbon nanotube nanocomposite films modified electrode for simultaneous voltammetric detection of D-glucose and D-xylose.

PubMed

Li, Liang; Liang, Bo; Li, Feng; Shi, Jianguo; Mascini, Marco; Lang, Qiaolin; Liu, Aihua

2013-04-15

In this paper, we first report the construction of Nafion/glucose oxidase (GOD)/xylose dehydrogenase displayed bacteria (XDH-bacteria)/multiwalled carbon nanotubes (MWNTs) modified electrode for simultaneous voltammetric determination of D-glucose and D-xylose. The optimal conditions for the immobilized enzymes were established. Both enzymes retained their good stability and activities. In the mixture solution of D-glucose and D-xylose containing coenzyme NAD⁺ (the oxidized form of nicotinamide adenine dinucleotide), the Nafion/GOD/XDH-bacteria/MWNTs modified electrode exhibited quasi-reversible oxidation-reduction peak at -0.5 V (vs. saturated calomel electrode, SCE) originating from the catalytic oxidation of D-glucose, and oxidation peak at +0.55 V(vs. SCE) responding to the oxidation of NADH (the reduced form of nicotinamide adenine dinucleotide) by the carbon nanotubes, where NADH is the resultant product of coenzyme NAD⁺ involved in the catalysis of D-xylose by XDH-displayed bacteria. For the proposed biosensor, cathodic peak current at -0.5 V was linear with the concentration of D-glucose within the range of 0.25-6 mM with a low detection limit of 0.1 mM D-glucose (S/N=3), and the anodic peak current at +0.55 V was linear with the concentration of d-xylose in the range of 0.25∼4 mM with a low detection limit of 0.1 mM D-xylose (S/N=3). Further, D-xylose and D-glucose did not interfere with each other. 300-fold excess saccharides including D-maltose, D-galactose, D-mannose, D-sucrose, D-fructose, D-cellobiose, and 60-fold excess L-arabinose, and common interfering substances (100-fold excess ascorbic acid, dopamine, uric acid) as well as 300-fold excess D-xylitol did not affect the detection of D-glucose and D-xylose (both 1 mM). Therefore, the proposed biosensor is stable, specific, reproducible, simple, rapid and cost-effective, which holds great potential in real applications. Copyright © 2012 Elsevier B.V. All rights reserved.

Polydimethylsiloxane/metal-organic frameworks coated stir bar sorptive extraction coupled to high performance liquid chromatography-ultraviolet detector for the determination of estrogens in environmental water samples.

PubMed

Hu, Cong; He, Man; Chen, Beibei; Zhong, Cheng; Hu, Bin

2013-10-04

In this work, three kinds of metal-organic frameworks (MOFs), MOF-5, MOF-199 and IRMOF-3, were introduced in stir bar sorptive extraction (SBSE) and novel polydimethylsiloxane (PDMS)/MOFs (including PDMS/MOF-5, PDMS/MOF-199 and PDMS/IRMOF-3) coated stir bars were prepared by sol-gel technique. These PDMS/MOFs coatings were characterized and critically compared for the extraction of seven target estrogens (17-β-estradiol, dienestrol, diethylstilbestrol, estrone, 4-t-octylphenol, bisphenol-A and 17α-ethynylestradiol) by SBSE, and the results showed that PDMS/IRMOF-3 exhibited highest extraction efficiency. Based on the above facts, a novel method of PDMS/IRMOF-3 coating SBSE-high performance liquid chromatography ultraviolet (HPLC-UV) detection was developed for the determination of seven target estrogens in environmental waters. Several parameters affecting extraction of seven target estrogens by SBSE (PDMS/IRMOF-3) including extraction time, stirring rate, pH, ionic strength, desorption solvent and desorption time were investigated. Under the optimal experimental conditions, the limits of detection (LODs, S/N=3) were found to be in the range of 0.15-0.35 μg/L. The linear range was 2-2,500 μg/L for 17α-ethynylestradiol and 1-2,500 μg/L for other estrogens. The relative standard deviations (RSDs) were in the range of 3.7-9.9% (n=8, c=20 μg/L) and the enrichment factors were from 30.3 to 55.6-fold (theoretical enrichment factor was 100-fold). The proposed method was successfully applied to the analysis of estrogens in environmental water samples, and quantitative recoveries were obtained for the spiking experiments. Copyright © 2013 Elsevier B.V. All rights reserved.

Miniaturizing and automation of free acidity measurements for uranium (VI)-HNO3 solutions: Development of a new sequential injection analysis for a sustainable radio-analytical chemistry.

PubMed

Néri-Quiroz, José; Canto, Fabrice; Guillerme, Laurent; Couston, Laurent; Magnaldo, Alastair; Dugas, Vincent

2016-10-01

A miniaturized and automated approach for the determination of free acidity in solutions containing uranium (VI) is presented. The measurement technique is based on the concept of sequential injection analysis with on-line spectroscopic detection. The proposed methodology relies on the complexation and alkalimetric titration of nitric acid using a pH 5.6 sodium oxalate solution. The titration process is followed by UV/VIS detection at 650nm thanks to addition of Congo red as universal pH indicator. Mixing sequence as well as method validity was investigated by numerical simulation. This new analytical design allows fast (2.3min), reliable and accurate free acidity determination of low volume samples (10µL) containing uranium/[H(+)] moles ratio of 1:3 with relative standard deviation of <7.0% (n=11). The linearity range of the free nitric acid measurement is excellent up to 2.77molL(-1) with a correlation coefficient (R(2)) of 0.995. The method is specific, presence of actinide ions up to 0.54molL(-1) does not interfere on the determination of free nitric acid. In addition to automation, the developed sequential injection analysis method greatly improves the standard off-line oxalate complexation and alkalimetric titration method by reducing thousand fold the required sample volume, forty times the nuclear waste per analysis as well as the analysis time by eight fold. These analytical parameters are important especially in nuclear-related applications to improve laboratory safety, personnel exposure to radioactive samples and to drastically reduce environmental impacts or analytical radioactive waste. Copyright © 2016 Elsevier B.V. All rights reserved.

Transition paths in single-molecule force spectroscopy

NASA Astrophysics Data System (ADS)

Cossio, Pilar; Hummer, Gerhard; Szabo, Attila

2018-03-01

In a typical single-molecule force spectroscopy experiment, the ends of the molecule of interest are connected by long polymer linkers to a pair of mesoscopic beads trapped in the focus of two laser beams. At constant force load, the total extension, i.e., the end-to-end distance of the molecule plus linkers, is measured as a function of time. In the simplest systems, the measured extension fluctuates about two values characteristic of folded and unfolded states, with occasional transitions between them. We have recently shown that molecular (un)folding rates can be recovered from such trajectories, with a small linker correction, as long as the characteristic time of the bead fluctuations is shorter than the residence time in the unfolded (folded) state. Here, we show that accurate measurements of the molecular transition path times require an even faster apparatus response. Transition paths, the trajectory segments in which the molecule (un)folds, are properly resolved only if the beads fluctuate more rapidly than the end-to-end distance of the molecule. Therefore, over a wide regime, the measured rates may be meaningful but not the transition path times. Analytic expressions for the measured mean transition path times are obtained for systems diffusing anisotropically on a two-dimensional free energy surface. The transition path times depend on the properties both of the molecule and of the pulling device.

Direct folding simulation of a long helix in explicit water

NASA Astrophysics Data System (ADS)

Gao, Ya; Lu, Xiaoliang; Duan, Lili; Zhang, Dawei; Mei, Ye; Zhang, John Z. H.

2013-05-01

A recently proposed Polarizable Hydrogen Bond (PHB) method has been employed to simulate the folding of a 53 amino acid helix (PDB ID 2KHK) in explicit water. Under PHB simulation, starting from a fully extended structure, the peptide folds into the native state as confirmed by measured time evolutions of radius of gyration, root mean square deviation (RMSD), and native hydrogen bond. Free energy and cluster analysis show that the folded helix is thermally stable under the PHB model. Comparison of simulation results under, respectively, PHB and standard nonpolarizable force field demonstrates that polarization is critical for stable folding of this long α-helix.

Gold nanoparticle-based RT-PCR and real-time quantitative RT-PCR assays for detection of Japanese encephalitis virus

NASA Astrophysics Data System (ADS)

Huang, Su-Hua; Yang, Tsuey-Ching; Tsai, Ming-Hong; Tsai, I.-Shou; Lu, Huang-Chih; Chuang, Pei-Hsin; Wan, Lei; Lin, Ying-Ju; Lai, Chih-Ho; Lin, Cheng-Wen

2008-10-01

Virus isolation and antibody detection are routinely used for diagnosis of Japanese encephalitis virus (JEV) infection, but the low level of transient viremia in some JE patients makes JEV isolation from clinical and surveillance samples very difficult. We describe the use of gold nanoparticle-based RT-PCR and real-time quantitative RT-PCR assays for detection of JEV from its RNA genome. We tested the effect of gold nanoparticles on four different PCR systems, including conventional PCR, reverse-transcription PCR (RT-PCR), and SYBR green real-time PCR and RT-PCR assays for diagnosis in the acute phase of JEV infection. Gold nanoparticles increased the amplification yield of the PCR product and shortened the PCR time compared to the conventional reaction. In addition, nanogold-based real-time RT-PCR showed a linear relationship between Ct and template amount using ten-fold dilutions of JEV. The nanogold-based RT-PCR and real-time quantitative RT-PCR assays were able to detect low levels (1-10 000 copies) of the JEV RNA genomes extracted from culture medium or whole blood, providing early diagnostic tools for the detection of low-level viremia in the acute-phase infection. The assays described here were simple, sensitive, and rapid approaches for detection and quantitation of JEV in tissue cultured samples as well as clinical samples.

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

Global environmental impacts of agricultural expansion: The need for sustainable and efficient practices

PubMed Central

Tilman, David

1999-01-01

The recent intensification of agriculture, and the prospects of future intensification, will have major detrimental impacts on the nonagricultural terrestrial and aquatic ecosystems of the world. The doubling of agricultural food production during the past 35 years was associated with a 6.87-fold increase in nitrogen fertilization, a 3.48-fold increase in phosphorus fertilization, a 1.68-fold increase in the amount of irrigated cropland, and a 1.1-fold increase in land in cultivation. Based on a simple linear extension of past trends, the anticipated next doubling of global food production would be associated with approximately 3-fold increases in nitrogen and phosphorus fertilization rates, a doubling of the irrigated land area, and an 18% increase in cropland. These projected changes would have dramatic impacts on the diversity, composition, and functioning of the remaining natural ecosystems of the world, and on their ability to provide society with a variety of essential ecosystem services. The largest impacts would be on freshwater and marine ecosystems, which would be greatly eutrophied by high rates of nitrogen and phosphorus release from agricultural fields. Aquatic nutrient eutrophication can lead to loss of biodiversity, outbreaks of nuisance species, shifts in the structure of food chains, and impairment of fisheries. Because of aerial redistribution of various forms of nitrogen, agricultural intensification also would eutrophy many natural terrestrial ecosystems and contribute to atmospheric accumulation of greenhouse gases. These detrimental environmental impacts of agriculture can be minimized only if there is much more efficient use and recycling of nitrogen and phosphorus in agroecosystems. PMID:10339530

Global environmental impacts of agricultural expansion: the need for sustainable and efficient practices.

PubMed

Tilman, D

1999-05-25

The recent intensification of agriculture, and the prospects of future intensification, will have major detrimental impacts on the nonagricultural terrestrial and aquatic ecosystems of the world. The doubling of agricultural food production during the past 35 years was associated with a 6.87-fold increase in nitrogen fertilization, a 3.48-fold increase in phosphorus fertilization, a 1.68-fold increase in the amount of irrigated cropland, and a 1.1-fold increase in land in cultivation. Based on a simple linear extension of past trends, the anticipated next doubling of global food production would be associated with approximately 3-fold increases in nitrogen and phosphorus fertilization rates, a doubling of the irrigated land area, and an 18% increase in cropland. These projected changes would have dramatic impacts on the diversity, composition, and functioning of the remaining natural ecosystems of the world, and on their ability to provide society with a variety of essential ecosystem services. The largest impacts would be on freshwater and marine ecosystems, which would be greatly eutrophied by high rates of nitrogen and phosphorus release from agricultural fields. Aquatic nutrient eutrophication can lead to loss of biodiversity, outbreaks of nuisance species, shifts in the structure of food chains, and impairment of fisheries. Because of aerial redistribution of various forms of nitrogen, agricultural intensification also would eutrophy many natural terrestrial ecosystems and contribute to atmospheric accumulation of greenhouse gases. These detrimental environmental impacts of agriculture can be minimized only if there is much more efficient use and recycling of nitrogen and phosphorus in agroecosystems.

Metolachlor Sorption and Degradation in Soil Amended with Fresh and Aged Biochars.

PubMed

Trigo, Carmen; Spokas, Kurt A; Hall, Kathleen E; Cox, Lucia; Koskinen, William C

2016-04-27

Addition of organic amendments such as biochar to soils can influence pesticide sorption-desorption processes and, in turn, the amount of pesticide readily availability for transport and biodegradation. Sorption-desorption processes are affected by both the physical and chemical properties of soils and pesticides, as well as soil-pesticide contact time, or aging. Changes in sorption-desorption of metolachlor with aging in soil amended with three macadamia nut shell biochars aged 0 (BCmac-fr), 1 year (BCmac-1yr), and 2 years (BCmac-2yr) and two wood biochars aged 0 (BCwood-fr) and 5 years (BCwood-5yr) were determined. Apparent sorption coefficient (Kd-app) values increased with incubation time to a greater extent in amended soil as compared to unamended soils; Kd-app increased by 1.2-fold for the unamended soil, 2.0-fold for BCwood-fr, 1.4-fold for BCwood-5yr, 2.4-fold for BCmac-fr, 2.5-fold for BCmac-1yr, and 1.9-fold for BCmac-4yr. The increase in calculated Kd-app value was the result of a 15% decrease in the metolachlor solution concentration extractable with CaCl2 solution with incubation time in soil as compared to a 50% decrease in amended soil with very little change in the sorbed concentration. Differences could possibly be due to diffusion to less accessible or stronger binding sites with time, a faster rate of degradation (in solution and on labile sites) than desorption, or a combination of the two in the amended soils. These data show that transport models would overpredict the depth of movement of metolachlor in soil if effects of aging or biochar amendments are not considered.

Fast, high peak capacity separations in comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry.

PubMed

Fitz, Brian D; Wilson, Ryan B; Parsons, Brendon A; Hoggard, Jamin C; Synovec, Robert E

2012-11-30

Peak capacity production is substantially improved for two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC×GC-TOFMS) and applied to the fast separation of a 28 component liquid test mixture, and two complex vapor samples (a 65 component volatile organic compound test mixture, and the headspace of warm ground coffee beans). A high peak capacity is achieved in a short separation time by selecting appropriate experimental conditions based on theoretical modeling of on-column band broadening, and by reducing the off-column band broadening by applying a narrow, concentrated injection pulse onto the primary column using high-speed cryo-focusing injection (HSCFI), referred to as thermal injection. A long, relatively narrow open tubular capillary column (20 m, 100 μm inner diameter (i.d.) with a 0.4 μm film thickness to benefit column capacity) was used as the primary column. The initial flow rate was 2 ml/min (60 cm/s average linear flow velocity) which is slightly below the optimal average linear gas velocity of 83 cm/s, due to the flow rate constraint of the TOFMS vacuum system. The oven temperature programming rate was 30°C/min. The secondary column (1.8m, 100 μm i.d. with a 0.1 μm film thickness) provided a relatively high peak capacity separation, concurrent with a significantly shorter modulation period, P(M), than commonly applied with the commercial instrument. With this GC×GC-TOFMS instrumental platform, compounds in the 28 component liquid test mixture provided a ∼7 min separation (with a ∼6.5 min separation time window), producing average peak widths of ∼600 ms full width half maximum (FWHM), resulting in a peak capacity on the primary column of ∼400 peaks (at unit resolution). Using a secondary column with a 500 ms P(M), average peak widths of ∼20 ms FWHM were achieved, thus providing a peak capacity of 15 peaks on the second dimension. Overall, an ideal orthogonal GC×GC peak capacity of ∼6000 peaks (at unit resolution) was achieved (or a β-corrected orthogonal peak capacity of ∼4400, at an average modulation ratio, M(R), of ∼2). This corresponds to an ideal orthogonal peak capacity production of ∼1000 peaks/min (or ∼700 peaks/min, β-corrected). For comparison, standard split/split-less injection techniques with a 1:100 split, when combined with standard GC×GC conditions typically provide a peak capacity production of ∼100 peaks/min, hence the instrumental platform we report provides a ∼7-fold to 10-fold improvement. Copyright © 2012 Elsevier B.V. All rights reserved.

Late Cenozoic Deformation in the Western Tarim Basin, NW China

NASA Astrophysics Data System (ADS)

Thompson, J. A.; Burbank, D. W.; Chen, J.; Li, T.

2009-12-01

The Tian Shan in NW China is one of the most active regions of intracontinental deformation in the world, accommodating a large fraction (~40%) of the shortening from the Indo-Eurasian collision. The western Tarim Basin, situated between the southern Tian Shan and Pamir Mountains, manifests this deformation through a series of east-west trending fault-related folds that have formed during the late Cenozoic. Previous studies in this region have focused on the kinematics, style, and timing of detachment folds related to folding within the foreland basin of the southern Tian Shan. In contrast, this study focuses on the deformation caused by fault-propagation folding resulting from the northward movement of the Pamir. The rates of deformation are calculated using a combination of optically stimulated luminescence (OSL) ages, structural mapping and differential GPS surveys of fault scarps and deformed terrace surfaces crossing active folds. OSL dating provides the time since the sediment was last exposed to daylight, i.e., time since burial. Consequently, OSL is useful for dating the abandonment of terrace surfaces due to tectonic (fold growth) or climatic events. OSL quartz samples were collected from silt lenses within gravel topping the terraces. Most of the quartz OSL signals are weak, thus several grain sizes (silt (4-11 µm, 8-15 µm) and sand (90-125 µm)) were analyzed and different integrations of the shine-down curves were explored to calculate equivalent doses. The implications for different equivalent doses and ages on the calculation of rates of deformation are also addressed.

Discretized torsional dynamics and the folding of an RNA chain.

PubMed

Fernández, A; Salthú, R; Cendra, H

1999-08-01

The aim of this work is to implement a discrete coarse codification of local torsional states of the RNA chain backbone in order to explore the long-time limit dynamics and ultimately obtain a coarse solution to the RNA folding problem. A discrete representation of the soft-mode dynamics is turned into an algorithm for a rough structure prediction. The algorithm itself is inherently parallel, as it evaluates concurrent folding possibilities by pattern recognition, but it may be implemented in a personal computer as a chain of perturbation-translation-renormalization cycles performed on a binary matrix of local topological constraints. This requires suitable representational tools and a periodic quenching of the dynamics for system renormalization. A binary coding of local topological constraints associated with each structural motif is introduced, with each local topological constraint corresponding to a local torsional state. This treatment enables us to adopt a computation time step far larger than hydrodynamic drag time scales. Accordingly, the solvent is no longer treated as a hydrodynamic drag medium. Instead we incorporate its capacity for forming local conformation-dependent dielectric domains. Each translation of the matrix of local topological constraints (LTM's) depends on the conformation-dependent local dielectric created by a confined solvent. Folding pathways are resolved as transitions between patterns of locally encoded structural signals which change within the 1 ns-100 ms time scale range. These coarse folding pathways are generated by a search at regular intervals for structural patterns in the LTM. Each pattern is recorded as a base-pairing pattern (BPP) matrix, a consensus-evaluation operation subject to a renormalization feedback loop. Since several mutually conflicting consensus evaluations might occur at a given time, the need arises for a probabilistic approach appropriate for an ensemble of RNA molecules. Thus, a statistical dynamics of consensus formation is determined by the time evolution of the base pairing probability matrix. These dynamics are generated for a functional RNA molecule, a representative of the so-called group I ribozymes, in order to test the model. The resulting ensemble of conformations is sharply peaked and the most probable structure features the predominance of all phylogenetically conserved intrachain helices tantamount to ribozyme function. Furthermore, the magnesium-aided cooperativity that leads to the shaping of the catalytic core is elucidated. Once the predictive folding algorithm has been implemented, the validity of the so-called "adiabatic approximation" is tested. This approximation requires that conformational microstates be lumped up into BPP's which are treated as quasiequilibrium states, while folding pathways are coarsely represented as sequences of BPP transitions. To test the validity of this adiabatic ansatz, a computation of the coarse Shannon information entropy sigma associated to the specific partition of conformation space into BPP's is performed taking into account the LTM evolution and contrasted with the adiabatic computation. The results reveal a subordination of torsional microstate dynamics to BPP transitions within time scales relevant to folding. This adiabatic entrainment in the long-time limit is thus identified as responsible for the expediency of the folding process.

GPU-based Branchless Distance-Driven Projection and Backprojection

PubMed Central

Liu, Rui; Fu, Lin; De Man, Bruno; Yu, Hengyong

2017-01-01

Projection and backprojection operations are essential in a variety of image reconstruction and physical correction algorithms in CT. The distance-driven (DD) projection and backprojection are widely used for their highly sequential memory access pattern and low arithmetic cost. However, a typical DD implementation has an inner loop that adjusts the calculation depending on the relative position between voxel and detector cell boundaries. The irregularity of the branch behavior makes it inefficient to be implemented on massively parallel computing devices such as graphics processing units (GPUs). Such irregular branch behaviors can be eliminated by factorizing the DD operation as three branchless steps: integration, linear interpolation, and differentiation, all of which are highly amenable to massive vectorization. In this paper, we implement and evaluate a highly parallel branchless DD algorithm for 3D cone beam CT. The algorithm utilizes the texture memory and hardware interpolation on GPUs to achieve fast computational speed. The developed branchless DD algorithm achieved 137-fold speedup for forward projection and 188-fold speedup for backprojection relative to a single-thread CPU implementation. Compared with a state-of-the-art 32-thread CPU implementation, the proposed branchless DD achieved 8-fold acceleration for forward projection and 10-fold acceleration for backprojection. GPU based branchless DD method was evaluated by iterative reconstruction algorithms with both simulation and real datasets. It obtained visually identical images as the CPU reference algorithm. PMID:29333480

Piezoelectric energy harvesting from heartbeat vibrations for leadless pacemakers

NASA Astrophysics Data System (ADS)

Ansari, M. H.; Karami, M. Amin

2015-12-01

This paper studies energy harvesting from heartbeat vibrations using fan-folded piezoelectric beams. The generated energy from the heartbeat can be used to power a leadless pacemaker. In order to utilize the available 3 dimensional space to the energy harvester, we chose the fan-folded design. The proposed device consists of several piezoelectric beams stacked on top of each other. The size for this energy harvester is 2 cm by 0.5 cm by 1 cm, which makes the natural frequency very high. High natural frequency is one major concern about the micro-scaled energy harvesters. By utilizing the fan-folded geometry and adding tip mass and link mass to the configuration, this natural frequency is reduced to the desired range. This fan-folded design makes it possible to generate more than 10 μW of power. The proposed device does not incorporate magnets and is thus Magnetic resonance imaging (MRI) compatible. Although our device is a linear energy harvester, it is shown that the device is relatively insensitive to the heartrate. The natural frequencies and the mode shapes of the device are calculated. An analytical solution is presented and the method is verified by experimental investigation. We use a closed loop shaker controller and a shaker to simulate the heartbeat vibrations. The developed analytical model is verified through comparison of theoretical and experimental tip displacement and acceleration frequency response functions.

Modeling and experimental verification of a fan-folded vibration energy harvester for leadless pacemakers

NASA Astrophysics Data System (ADS)

Ansari, M. H.; Karami, M. Amin

2016-03-01

This paper studies energy harvesting from heartbeat vibrations for powering leadless pacemakers. Unlike traditional pacemakers, leadless pacemakers are implanted inside the heart and the pacemaker is in direct contact with the myocardium. A leadless pacemaker is in the shape of a cylinder. Thus, in order to utilize the available 3-dimensional space for the energy harvester, we choose a fan-folded 3D energy harvester. The proposed device consists of several piezoelectric beams stacked on top of each other. The volume of the energy harvester is 1 cm3 and its dimensions are 2 cm × 0.5 cm × 1 cm. Although high natural frequency is generally a major concern with micro-scale energy harvesters, by utilizing the fan-folded geometry and adding tip mass and link mass to the configuration, we reduced the natural frequency to the desired range. This fan-folded design makes it possible to generate more than 10 μ W of power per cubic centimeter. The proposed device is compatible with Magnetic Resonance Imaging. Although the proposed device is a linear energy harvester, it is relatively insensitive to the heart rate. The natural frequencies and the mode shapes of the device are calculated analytically. The accuracy of the analytical model is verified by experimental investigations. We use a closed loop shaker system to precisely replicate heartbeat vibrations in vitro.

GPU-based Branchless Distance-Driven Projection and Backprojection.

PubMed

Liu, Rui; Fu, Lin; De Man, Bruno; Yu, Hengyong

2017-12-01

Projection and backprojection operations are essential in a variety of image reconstruction and physical correction algorithms in CT. The distance-driven (DD) projection and backprojection are widely used for their highly sequential memory access pattern and low arithmetic cost. However, a typical DD implementation has an inner loop that adjusts the calculation depending on the relative position between voxel and detector cell boundaries. The irregularity of the branch behavior makes it inefficient to be implemented on massively parallel computing devices such as graphics processing units (GPUs). Such irregular branch behaviors can be eliminated by factorizing the DD operation as three branchless steps: integration, linear interpolation, and differentiation, all of which are highly amenable to massive vectorization. In this paper, we implement and evaluate a highly parallel branchless DD algorithm for 3D cone beam CT. The algorithm utilizes the texture memory and hardware interpolation on GPUs to achieve fast computational speed. The developed branchless DD algorithm achieved 137-fold speedup for forward projection and 188-fold speedup for backprojection relative to a single-thread CPU implementation. Compared with a state-of-the-art 32-thread CPU implementation, the proposed branchless DD achieved 8-fold acceleration for forward projection and 10-fold acceleration for backprojection. GPU based branchless DD method was evaluated by iterative reconstruction algorithms with both simulation and real datasets. It obtained visually identical images as the CPU reference algorithm.

A Dual-Channel Acquisition Method Based on Extended Replica Folding Algorithm for Long Pseudo-Noise Code in Inter-Satellite Links.

PubMed

Zhao, Hongbo; Chen, Yuying; Feng, Wenquan; Zhuang, Chen

2018-05-25

Inter-satellite links are an important component of the new generation of satellite navigation systems, characterized by low signal-to-noise ratio (SNR), complex electromagnetic interference and the short time slot of each satellite, which brings difficulties to the acquisition stage. The inter-satellite link in both Global Positioning System (GPS) and BeiDou Navigation Satellite System (BDS) adopt the long code spread spectrum system. However, long code acquisition is a difficult and time-consuming task due to the long code period. Traditional folding methods such as extended replica folding acquisition search technique (XFAST) and direct average are largely restricted because of code Doppler and additional SNR loss caused by replica folding. The dual folding method (DF-XFAST) and dual-channel method have been proposed to achieve long code acquisition in low SNR and high dynamic situations, respectively, but the former is easily affected by code Doppler and the latter is not fast enough. Considering the environment of inter-satellite links and the problems of existing algorithms, this paper proposes a new long code acquisition algorithm named dual-channel acquisition method based on the extended replica folding algorithm (DC-XFAST). This method employs dual channels for verification. Each channel contains an incoming signal block. Local code samples are folded and zero-padded to the length of the incoming signal block. After a circular FFT operation, the correlation results contain two peaks of the same magnitude and specified relative position. The detection process is eased through finding the two largest values. The verification takes all the full and partial peaks into account. Numerical results reveal that the DC-XFAST method can improve acquisition performance while acquisition speed is guaranteed. The method has a significantly higher acquisition probability than folding methods XFAST and DF-XFAST. Moreover, with the advantage of higher detection probability and lower false alarm probability, it has a lower mean acquisition time than traditional XFAST, DF-XFAST and zero-padding.

Modulation of Folding Internal Friction by Local and Global Barrier Heights.

PubMed

Zheng, Wenwei; de Sancho, David; Best, Robert B

2016-03-17

Recent experiments have revealed an unexpected deviation from a first power dependence of protein relaxation times on solvent viscosity, an effect that has been attributed to "internal friction". One clear source of internal friction in protein dynamics is the isomerization of dihedral angles. A key outstanding question is whether the global folding barrier height influences the measured internal friction, based on the observation that the folding rates of fast-folding proteins, with smaller folding free energy barriers, tend to exhibit larger internal friction. Here, by studying two alanine-based peptides, we find that systematic variation of global folding barrier heights has little effect on the internal friction for folding rates. On the other hand, increasing local torsion angle barriers leads to increased internal friction, which is consistent with solvent memory effects being the origin of the viscosity dependence. Thus, it appears that local torsion transitions determine the viscosity dependence of the diffusion coefficient on the global coordinate and, in turn, internal friction effects on the folding rate.

Substrate Cooperativity in Marine Luciferases

PubMed Central

Tzertzinis, George; Schildkraut, Ezra; Schildkraut, Ira

2012-01-01

Marine luciferases are increasingly used as reporters to study gene regulation. These luciferases have utility in bioluminescent assay development, although little has been reported on their catalytic properties in response to substrate concentration. Here, we report that the two marine luciferases from the copepods, Gaussia princeps (GLuc) and Metridia longa (MLuc) were found, surprisingly, to produce light in a cooperative manner with respect to their luciferin substrate concentration; as the substrate concentration was decreased 10 fold the rate of light production decreased 1000 fold. This positive cooperative effect is likely a result of allostery between the two proposed catalytic domains found in Gaussia and Metridia. In contrast, the marine luciferases from Renilla reniformis (RLuc) and Cypridina noctiluca (CLuc) demonstrate a linear relationship between the concentration of their respective luciferin and the rate of light produced. The consequences of these enzyme responses are discussed. PMID:22768230

The increase in animal mortality risk following exposure to sparsely ionizing radiation is not linear quadratic with dose

DOE PAGES

Haley, Benjamin M.; Paunesku, Tatjana; Grdina, David J.; ...

2015-12-09

The US government regulates allowable radiation exposures relying, in large part, on the seventh report from the committee to estimate the Biological Effect of Ionizing Radiation (BEIR VII), which estimated that most contemporary exposures- protracted or low-dose, carry 1.5 fold less risk of carcinogenesis and mortality per Gy than acute exposures of atomic bomb survivors. This correction is known as the dose and dose rate effectiveness factor for the life span study of atomic bomb survivors (DDREF LSS). As a result, it was calculated by applying a linear-quadratic dose response model to data from Japanese atomic bomb survivors and amore » limited number of animal studies.« less

The increase in animal mortality risk following exposure to sparsely ionizing radiation is not linear quadratic with dose

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

Haley, Benjamin M.; Paunesku, Tatjana; Grdina, David J.

The US government regulates allowable radiation exposures relying, in large part, on the seventh report from the committee to estimate the Biological Effect of Ionizing Radiation (BEIR VII), which estimated that most contemporary exposures- protracted or low-dose, carry 1.5 fold less risk of carcinogenesis and mortality per Gy than acute exposures of atomic bomb survivors. This correction is known as the dose and dose rate effectiveness factor for the life span study of atomic bomb survivors (DDREF LSS). As a result, it was calculated by applying a linear-quadratic dose response model to data from Japanese atomic bomb survivors and amore » limited number of animal studies.« less

Synthetic oligorotaxanes exert high forces when folding under mechanical load

NASA Astrophysics Data System (ADS)

Sluysmans, Damien; Hubert, Sandrine; Bruns, Carson J.; Zhu, Zhixue; Stoddart, J. Fraser; Duwez, Anne-Sophie

2018-01-01

Folding is a ubiquitous process that nature uses to control the conformations of its molecular machines, allowing them to perform chemical and mechanical tasks. Over the years, chemists have synthesized foldamers that adopt well-defined and stable folded architectures, mimicking the control expressed by natural systems1,2. Mechanically interlocked molecules, such as rotaxanes and catenanes, are prototypical molecular machines that enable the controlled movement and positioning of their component parts3-5. Recently, combining the exquisite complexity of these two classes of molecules, donor-acceptor oligorotaxane foldamers have been synthesized, in which interactions between the mechanically interlocked component parts dictate the single-molecule assembly into a folded secondary structure6-8. Here we report on the mechanochemical properties of these molecules. We use atomic force microscopy-based single-molecule force spectroscopy to mechanically unfold oligorotaxanes, made of oligomeric dumbbells incorporating 1,5-dioxynaphthalene units encircled by cyclobis(paraquat-p-phenylene) rings. Real-time capture of fluctuations between unfolded and folded states reveals that the molecules exert forces of up to 50 pN against a mechanical load of up to 150 pN, and displays transition times of less than 10 μs. While the folding is at least as fast as that observed in proteins, it is remarkably more robust, thanks to the mechanically interlocked structure. Our results show that synthetic oligorotaxanes have the potential to exceed the performance of natural folding proteins.

Late Mesozoic deformations of the Verkhoyansk-Kolyma orogenic belt, Northeast Russia

NASA Astrophysics Data System (ADS)

Fridovsky, Valery

2016-04-01

The Verkhoyansk-Kolyma orogenic belt marks the boundary between the Kolyma-Omolon superterrane (microcontinent) and the submerged eastern margin of the North Asian craton. The orogenic system is remark able for its large number of economically viable gold deposits (Natalka, Pavlik, Rodionovskoe, Drazhnoe, Bazovskoe, Badran, Malo-Tarynskoe, etc.). The Verkhoyansk - Kolyma orogenic belt is subdivided into Kular-Nera and the Polousny-Debin terranes. The Kular-Nera terrane is mainly composed of the Upper Permian, Triassic, and Lower Jurassic black shales that are metamorphosed at lower greenschist facies conditions. The Charky-Indigirka and the Chai-Yureya faults separate the Kular-Nera from the Polousny-Debin terrane that is predominantly composed of the Jurassic flyschoi dturbidites. The deformation structure of the region evolved in association with several late Mesozoic tectonic events that took place in the north-eastern part ofthe Paleo-Pacific. In Late Jurassic-Early Cretaceous several generations of fold and thrust systems were formed due to frontal accretion of the Kolyma-Omolon superterrane to the eastern margin of the North Asian craton.Thrusting and folding was accompanied by granitic magmatism, metamorphic reworking of the Late Paleozoic and the Early Mesozoic sedimentary rocks, and formation of Au-Sn-W mineralization. Three stages of deformation related to frontal accretion can be distinguished. First stage D1 has developed in the north-eastern part of the Verkhoyansk - Kolyma orogenic belt. Early tight and isoclinal folds F1 and assosiated thrusts are characteristic of D1. Major thrusts, linear concentric folds F2 and cleavage were formed during D2. The main ore-controlling structures are thrust faults forming imbricate fan systems. Frontal and oblique ramps and systems of bedding and cross thrusts forming duplexes are common. It is notable that mineralized tectonized zones commonly develop along thrusts at the contacts of rocks of contrasting competence. The superimposed structures are recognized from the early cleavage deformations. Folds F3 are often chevron type, open or tight. D1, D2 and D3 deformations are coaxial. In the Late-Neocomian-Aptian the Kolyma-Omolon superterrane started moving to the west. As a result, the thrust faults were reactivated with sinistral strike-slip motions along fault planes. At that time, granitoids of the North and Transverse belts were emplaced in the northwestern part of the Kolyma-Omolon superterrane. The strike slip faults were associated with cross open folds. The postacrettionary stage is associated with the development of the Albian-Late Cretaceous Okhotsk-Chukotka subduction zone. During this stage strike-slip faults and associated deformation structures were superimposed upon accretion-related tectonic structures of the Verkhoyansk - Kolyma orogenic belt.

Effective Potentials for Folding Proteins

NASA Astrophysics Data System (ADS)

Chen, Nan-Yow; Su, Zheng-Yao; Mou, Chung-Yu

2006-02-01

A coarse-grained off-lattice model that is not biased in any way to the native state is proposed to fold proteins. To predict the native structure in a reasonable time, the model has included the essential effects of water in an effective potential. Two new ingredients, the dipole-dipole interaction and the local hydrophobic interaction, are introduced and are shown to be as crucial as the hydrogen bonding. The model allows successful folding of the wild-type sequence of protein G and may have provided important hints to the study of protein folding.

The Reflexes of the Fundus Oculi

PubMed Central

Ballantyne, A. J.

1940-01-01

The fundus reflexes reveal, in a manner not yet completely understood, the texture and contour of the reflecting surfaces and the condition of the underlying tissues. In this way they may play an important part in the biomicroscopy of the eye. The physiological reflexes are seen at their best in the eyes of young subjects, in well-pigmented eyes, with undilated pupils and with emmetropic refraction. Their absence during the first two decades, or their presence after the forties, their occurrence in one eye only, their appearance, disappearance or change of character should suggest the possibility of some pathological state. The investigation and interpretation of the reflexes are notably assisted by comparing the appearances seen with long and short wave lights such as those of the sodium and mercury vapour lamps, in addition to the usual ophthalmoscopic lights. Most of the surface reflexes disappear in the light of the sodium lamp, sometimes revealing important changes in the deeper layers of the retina and choroid. The physiological reflexes, chiefly formed on the surface of the internal limiting membrane, take the forms of the familiar watered silk or patchy reflexes, the peri-macular halo, the fan reflex in the macular depression and the reflex from the foveal pit. The watered silk or patchy reflexes often show a delicate striation which follows the pattern of the nerve-fibre layer, or there may be a granular or criss-cross texture. Reflexes which entirely lack these indications of “texture” should be considered as possibly pathological. This applies to the “beaten metal” reflexes and to those formed on the so-called hyaloid membrane. The occurrence of physiological reflexes in linear form is doubtful, and the only admittedly physiological punctate reflexes are the so-called Gunn's dots. Surface reflexes which are broken up into small points or flakes are pathological, and are most frequently seen in the central area of the fundus in cases of pigmentary degeneration of the retina or after the subsidence of severe retinitis or retino-choroiditis. A mirror reflex from the layer of pigmented epithelium or from the external limiting membrane is sometimes recognizable in normal eyes, especially in the brunette fundus. In such, it forms the background to a striking picture of the fine circumfoveal vessels. Pathological reflexes from the level of the pigmented epithelium or of the external limiting membrane are also observed, and these often present a granular, frosted or crystalline appearance. They may indicate a senile change, or result from trauma or from retino-choroidal degeneraion. Somewhat similar reflexes may sometimes be present as small frosted patches anterior to the retinal vessels. Linear sinuous, whether appearing in annular form, as straight needles, as broader single sinuous lines, as the tapering, branched double reflexes of Vogt, or in association with traction or pressure folds, in the retina, are probably always pathological. By the use of selected light of long and short wave lengths, it can be shown that intraretinal or true retinal folds may exist with or without the surface reflexes which indicate a corresponding folding of the internal limiting membrane. On the other hand, superficial linear reflexes of various types may occur without evidence of retinal folding. Annular reflexes usually accompany a rounded elevation of the retina due to tumour, hæmorrhage or exudate, but may indicate the presence of rounded depressions; traction folds occur where there is choroido-retinal scarring, or in association with macular hole or cystic degeneraion at the macula; pressure folds in cases of orbital cyst, abscess or neoplasm; and the other linear reflexes in association with papillo-retinal œdema, for example, in retrobulbar neuritis, in hypertensive neuro-retinitis, in contusio bulbi and in anterior uveitis. Punctate reflexes, other than Gunn's dots, are also pathological. They may occur as one variety of “fragmented” surface reflexes, or as evidence of the presence of some highly refractile substance, such as cholesterin or calcium carbonate, in a retinal exudate or other lesion. It is characteristic of the pathological reflexes that they come and go and change their character according to the progress of the pathological condition. The linear reflexes in particular may change from one from to another, and may be finally transformed into surface reflexes of physiological character. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8Fig. 9Fig. 10Fig. 11Fig. 12Fig. 13Fig. 14Fig. 15Fig. 16Fig. 17Fig. 18Fig. 19Fig. 20Fig. 21Fig. 22Fig. 23Fig. 24Fig. 25Fig. 26 PMID:19992307

Multi-walled carbon nanotube-induced gene signatures in the mouse lung: potential predictive value for human lung cancer risk and prognosis

PubMed Central

Guo, Nancy L; Wan, Ying-Wooi; Denvir, James; Porter, Dale W; Pacurari, Maricica; Wolfarth, Michael G; Castranova, Vincent; Qian, Yong

2012-01-01

Concerns over the potential for multi-walled carbon nanotubes (MWCNT) to induce lung carcinogenesis have emerged. This study sought to (1) identify gene expression signatures in the mouse lungs following pharyngeal aspiration of well-dispersed MWCNT and (2) determine if these genes were associated with human lung cancer risk and progression. Genome-wide mRNA expression profiles were analyzed in mouse lungs (n=160) exposed to 0, 10, 20, 40, or 80 µg of MWCNT by pharyngeal aspiration at 1, 7, 28, and 56 days post-exposure. By using pairwise-Statistical Analysis of Microarray (SAM) and linear modeling, 24 genes were selected, which have significant changes in at least two time points, have a more than 1.5 fold change at all doses, and are significant in the linear model for the dose or the interaction of time and dose. Additionally, a 38-gene set was identified as related to cancer from 330 genes differentially expressed at day 56 post-exposure in functional pathway analysis. Using the expression profiles of the cancer-related gene set in 8 mice at day 56 post-exposure to 10 µg of MWCNT, a nearest centroid classification accurately predicts human lung cancer survival with a significant hazard ratio in training set (n=256) and test set (n=186). Furthermore, both gene signatures were associated with human lung cancer risk (n=164) with significant odds ratios. These results may lead to development of a surveillance approach for early detection of lung cancer and prognosis associated with MWCNT in the workplace. PMID:22891886

Minimally-Invasive, Image-Guided Cochlear Implantation Surgery: First report of clinical implementation

PubMed Central

Labadie, Robert F; Balachandran, Ramya; Noble, Jack H; Blachon, Grégoire S; Mitchell, Jason E; Reda, Fitsum A; Dawant, Benoit M; Fitzpatrick, J Michael

2015-01-01

OBJECTIVE Minimally-invasive image-guided approach to cochlear implantation (CI) involves drilling a narrow, linear tunnel to the cochlea. Reported herein is the first clinical implementation of this approach. STUDY DESIGN Prospective, cohort study. METHODS On preoperative CT, a safe linear trajectory through the facial recess targeting the scala tympani was planned. Intraoperatively, fiducial markers were bone-implanted, a second CT was acquired, and the trajectory was transferred from preoperative to intraoperative CT. A customized microstereotactic frame was rapidly designed and constructed to constrain a surgical drill along the desired trajectory. Following sterilization, the frame was employed to drill the tunnel to the middle ear. After lifting a tympanomeatal flap and performing a cochleostomy, the electrode array was threaded through the drilled tunnel and into the cochlea. RESULTS Eight of nine patients were successfully implanted using the proposed approach with six insertions completely within scala tympani. Traditional mastoidectomy was performed on one patient following difficulty threading the electrode array via the narrow tunnel. Other difficulties encountered included use of the back-up implant when an electrode was dislodged during threading via the tunnel, tip fold-over, and facial nerve paresis (House-Brackmann II/VII at 12 months) secondary to heat during drilling. Average time of intervention was 182±36 minutes. CONCLUSION Minimally-invasive, image-guided CI is clinically achievable. Further clinical study is necessary to address technological difficulties during drilling and insertion and to assess potential benefits including decreased time of intervention, standardization of surgical intervention, and decreased tissue dissection potentially leading to shorter recovery and earlier implant activation. PMID:24272427

Long-term sorption of halogenated organic chemicals by aquifer material. 1. Equilibrium

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

Ball, W.P.; Roberts, P.V.

1991-07-01

The sorption of tetrachloroethene (PCE) and 1,2,4,5-tetrachlorobenzene (TeCB) was studied on sandy aquifer material from Borden, ON, by using a batch methodology designed to accurately measure sorption over long equilibration periods. Autoclaving was effective in inhibiting biotransformation, and use of fire-sealed glass ampules precluded volatilization losses. Data analysis techniques were developed to accurately account for partitioning to sample headspace and other losses. Sorption isotherms for PCE and TeCB with Borden solids deviated from linearity when a 4-5 order of magnitude range in aqueous concentration was considered. However, in the dilute range (<50 {mu}/l), the deviations from linearity were inconsequential. Themore » sorption of TeCB was approximately 40 times stronger than for PCE, in qualitative accordance with TeCB's approximately 100-fold greater octanol-water partitioning coefficient. For a given solute, the distribution coefficients differed by a factor of 30 among the various size fractions, being greatest for the largest grains. For most Borden solids, the long-term sorption of PCE and TeCB exceeded by more than 1 order of magnitude the predictions of generalized correlations based on hydrophobic partitioning into organic matter. This difference is believed to be partially the result of mineral contributions to sorption, but may also reflect unattainment of equilibrium in previously regressed results - in this study, contact times on the order of tens to hundreds of days were required. For Borden solids, pulverization of solid samples was shown to be a viable expedient to obviate the need for excessively long equilibrations.« less

Use of low volatility mobile phases in electroosmotic thin-layer chromatography.

PubMed

Berezkin, V G; Balushkin, A O; Tyaglov, B V; Litvin, E F

2005-08-19

A variant of electroosmotic thin-layer chromatography is suggested with the use of low volatility compounds as mobile phases aimed at drastically decreasing the evaporation of the mobile phase and improving the reproducibility of the method. The linear movement velocity of zones of separated compounds is experimentally shown to increase 2-12-fold in electroosmotic chromatography (compared to similar values in traditional TLC). The separation efficiency is also considerably increased.

Rise-Time of FRET-Acceptor Fluorescence Tracks Protein Folding

PubMed Central

Lindhoud, Simon; Westphal, Adrie H.; van Mierlo, Carlo P. M.; Visser, Antonie J. W. G.; Borst, Jan Willem

2014-01-01

Uniform labeling of proteins with fluorescent donor and acceptor dyes with an equimolar ratio is paramount for accurate determination of Förster resonance energy transfer (FRET) efficiencies. In practice, however, the labeled protein population contains donor-labeled molecules that have no corresponding acceptor. These FRET-inactive donors contaminate the donor fluorescence signal, which leads to underestimation of FRET efficiencies in conventional fluorescence intensity and lifetime-based FRET experiments. Such contamination is avoided if FRET efficiencies are extracted from the rise time of acceptor fluorescence upon donor excitation. The reciprocal value of the rise time of acceptor fluorescence is equal to the decay rate of the FRET-active donor fluorescence. Here, we have determined rise times of sensitized acceptor fluorescence to study the folding of double-labeled apoflavodoxin molecules and show that this approach tracks the characteristics of apoflavodoxinʼs complex folding pathway. PMID:25535076

Thermodynamic and kinetic characterization of a beta-hairpin peptide in solution: an extended phase space sampling by molecular dynamics simulations in explicit water.

PubMed

Daidone, Isabella; Amadei, Andrea; Di Nola, Alfredo

2005-05-15

The folding of the amyloidogenic H1 peptide MKHMAGAAAAGAVV taken from the syrian hamster prion protein is explored in explicit aqueous solution at 300 K using long time scale all-atom molecular dynamics simulations for a total simulation time of 1.1 mus. The system, initially modeled as an alpha-helix, preferentially adopts a beta-hairpin structure and several unfolding/refolding events are observed, yielding a very short average beta-hairpin folding time of approximately 200 ns. The long time scale accessed by our simulations and the reversibility of the folding allow to properly explore the configurational space of the peptide in solution. The free energy profile, as a function of the principal components (essential eigenvectors) of motion, describing the main conformational transitions, shows the characteristic features of a funneled landscape, with a downhill surface toward the beta-hairpin folded basin. However, the analysis of the peptide thermodynamic stability, reveals that the beta-hairpin in solution is rather unstable. These results are in good agreement with several experimental evidences, according to which the isolated H1 peptide adopts very rapidly in water beta-sheet structure, leading to amyloid fibril precipitates [Nguyen et al., Biochemistry 1995;34:4186-4192; Inouye et al., J Struct Biol 1998;122:247-255]. Moreover, in this article we also characterize the diffusion behavior in conformational space, investigating its relations with folding/unfolding conditions. Copyright 2005 Wiley-Liss, Inc.

Pharmacokinetic interaction study of sulphasalazine in healthy subjects and the impact of curcumin as an in vivo inhibitor of BCRP

PubMed Central

Kusuhara, Hiroyuki; Furuie, Hidetoshi; Inano, Akihiro; Sunagawa, Akihiro; Yamada, Saiko; Wu, Chunyong; Fukizawa, Shinya; Morimoto, Nozomi; Ieiri, Ichiro; Morishita, Mariko; Sumita, Kiminobu; Mayahara, Hiroshi; Fujita, Takuya; Maeda, Kazuya; Sugiyama, Yuichi

2012-01-01

BACKGROUND AND PURPOSE An ATP-binding cassette (ABC) transporter, breast cancer resistance protein (BCRP)/ABCG2, limits oral bioavailability of sulphasalazine. Here we examined the effect of curcumin, the principal curcuminoid of turmeric, on oral bioavailability of microdoses and therapeutic doses of sulphasalazine in humans. EXPERIMENTAL APPROACH Effects of curcumin were measured on the ATP-dependent sulphasalazine uptake by hBCRP-expressing membrane vesicles and on oral bioavailability of sulphasalazine in wild-type and Bcrp(–/–) mice. Eight healthy Japanese subjects received an oral dose of sulphasalazine suspension (100 µg) or tablets (2 g) alone or after curcumin tablets (2 g). Uptake of sulphasalazine was studied in HEK293 cells transfected with the influx transporter (OATP)2B1. KEY RESULTS Curcumin was a potent hBCRP inhibitor in vitro (Ki 0.70 ± 0.41 µM). Curcumin increased the area under the curve (AUC)0–8 of plasma sulphasalazine eightfold in wild-type mice at 300 and 400 mg·kg−1, but not in Bcrp(–/–) mice. Curcumin increased AUC0–24 of plasma sulphasalazine 2.0-fold at microdoses and 3.2-fold at therapeutic doses in humans. Non-linearity of the dose–exposure relationship was observed between microdoses and therapeutic doses of sulphasalazine. Sulphasalazine was a substrate for OATP2B1 (Km 1.7 ± 0.3 µM). Its linear index (dose/Km) at the therapeutic dose was high and may saturate OATP2B1. CONCLUSIONS AND IMPLICATIONS Curcumin can be used to investigate effects of BCRP on oral bioavailability of drugs in humans. Besides the limited dissolution, OATP2B1 saturation is a possible mechanism underlying non-linearity in the dose–exposure relationship of sulphasalazine. PMID:22300367

Accurately controlled sequential self-folding structures by polystyrene film

NASA Astrophysics Data System (ADS)

Deng, Dongping; Yang, Yang; Chen, Yong; Lan, Xing; Tice, Jesse

2017-08-01

Four-dimensional (4D) printing overcomes the traditional fabrication limitations by designing heterogeneous materials to enable the printed structures evolve over time (the fourth dimension) under external stimuli. Here, we present a simple 4D printing of self-folding structures that can be sequentially and accurately folded. When heated above their glass transition temperature pre-strained polystyrene films shrink along the XY plane. In our process silver ink traces printed on the film are used to provide heat stimuli by conducting current to trigger the self-folding behavior. The parameters affecting the folding process are studied and discussed. Sequential folding and accurately controlled folding angles are achieved by using printed ink traces and angle lock design. Theoretical analyses are done to guide the design of the folding processes. Programmable structures such as a lock and a three-dimensional antenna are achieved to test the feasibility and potential applications of this method. These self-folding structures change their shapes after fabrication under controlled stimuli (electric current) and have potential applications in the fields of electronics, consumer devices, and robotics. Our design and fabrication method provides an easy way by using silver ink printed on polystyrene films to 4D print self-folding structures for electrically induced sequential folding with angular control.

Folding kinetics of WW domains with the united residue force field for bridging microscopic motions and experimental measurements

PubMed Central

Zhou, Rui; Maisuradze, Gia G.; Suñol, David; Todorovski, Toni; Macias, Maria J.; Xiao, Yi; Scheraga, Harold A.; Czaplewski, Cezary; Liwo, Adam

2014-01-01

To demonstrate the utility of the coarse-grained united-residue (UNRES) force field to compare experimental and computed kinetic data for folding proteins, we have performed long-time millisecond-timescale canonical Langevin molecular dynamics simulations of the triple β-strand from the Formin binding protein 28 WW domain and six nonnatural variants, using UNRES. The results have been compared with available experimental data in both a qualitative and a quantitative manner. Complexities of the folding pathways, which cannot be determined experimentally, were revealed. The folding mechanisms obtained from the simulated folding kinetics are in agreement with experimental results, with a few discrepancies for which we have accounted. The origins of single- and double-exponential kinetics and their correlations with two- and three-state folding scenarios are shown to be related to the relative barrier heights between the various states. The rate constants obtained from time profiles of the fractions of the native, intermediate, and unfolded structures, and the kinetic equations fitted to them, correlate with the experimental values; however, they are about three orders of magnitude larger than the experimental ones for most of the systems. These differences are in agreement with the timescale extension derived by scaling down the friction of water and averaging out the fast degrees of freedom when passing from all-atom to a coarse-grained representation. Our results indicate that the UNRES force field can provide accurate predictions of folding kinetics of these WW domains, often used as models for the study of the mechanisms of proein folding. PMID:25489078

Folding kinetics of WW domains with the united residue force field for bridging microscopic motions and experimental measurements.

PubMed

Zhou, Rui; Maisuradze, Gia G; Suñol, David; Todorovski, Toni; Macias, Maria J; Xiao, Yi; Scheraga, Harold A; Czaplewski, Cezary; Liwo, Adam

2014-12-23

To demonstrate the utility of the coarse-grained united-residue (UNRES) force field to compare experimental and computed kinetic data for folding proteins, we have performed long-time millisecond-timescale canonical Langevin molecular dynamics simulations of the triple β-strand from the Formin binding protein 28 WW domain and six nonnatural variants, using UNRES. The results have been compared with available experimental data in both a qualitative and a quantitative manner. Complexities of the folding pathways, which cannot be determined experimentally, were revealed. The folding mechanisms obtained from the simulated folding kinetics are in agreement with experimental results, with a few discrepancies for which we have accounted. The origins of single- and double-exponential kinetics and their correlations with two- and three-state folding scenarios are shown to be related to the relative barrier heights between the various states. The rate constants obtained from time profiles of the fractions of the native, intermediate, and unfolded structures, and the kinetic equations fitted to them, correlate with the experimental values; however, they are about three orders of magnitude larger than the experimental ones for most of the systems. These differences are in agreement with the timescale extension derived by scaling down the friction of water and averaging out the fast degrees of freedom when passing from all-atom to a coarse-grained representation. Our results indicate that the UNRES force field can provide accurate predictions of folding kinetics of these WW domains, often used as models for the study of the mechanisms of proein folding.

Map and data for Quaternary faults and folds in Washington state

USGS Publications Warehouse

Lidke, David J.; Johnson, Samuel Y.; McCrory, Patricia A.; Personius, Stephen F.; Nelson, Alan R.; Dart, Richard L.; Bradley, Lee-Ann; Haller, Kathleen M.; Machette, Michael N.

2004-01-01

The map shows faults and folds in Washington State that exhibit evidence of Quaternary deformation and includes data on timing of most recent movement, sense of movement, slip rate, and continuity of surface expression.

Fracture related-fold patterns analysis and hydrogeological implications: Insight from fault-propagation fold in Northwestern of Tunisia

NASA Astrophysics Data System (ADS)

Sanai, L.; Chenini, I.; Ben Mammou, A.; Mercier, E.

2015-01-01

The spatial distribution of fracturing in hard rocks is extremely related to the structural profile and traduces the kinematic evolution. The quantitative and qualitative analysis of fracturing combined to GIS techniques seem to be primordial and efficient in geometric characterization of lineament's network and to reconstruct the relative timing and interaction of the folding and fracturing histories. Also a detailed study of the area geology, lithology, tectonics, is primordial for any hydrogeological study. For that purpose we used a structural approach that consist in comparison between fracture sets before and after unfolding completed by aerospace data and DEM generated from topographic map. The above methodology applied in this study carried out in J. Rebia located in Northwestern of Tunisia demonstrated the heterogeneity of fracturing network and his relation with the fold growth throught time and his importance on groundwater flow.

Influence of Morinda citrifolia (Noni) on Expression of DNA Repair Genes in Cervical Cancer Cells.

PubMed

Gupta, Rakesh Kumar; Bajpai, Deepti; Singh, Neeta

2015-01-01

Previous studies have suggested that Morinda citrifolia (Noni) has potential to reduce cancer risk. The purpose of this study was to investigate the effect of Noni, cisplatin, and their combination on DNA repair genes in the SiHa cervical cancer cell line. SiHa cells were cultured and treated with 10% Noni, 10 μg/dl cisplatin or their combination for 24 hours. Post culturing, the cells were pelleted, RNA extracted, and processed for investigating DNA repair genes by real time PCR. The expression of nucleotide excision repair genes ERCC1, ERCC2, and ERCC4 and base excision repair gene XRCC1 was increased 4 fold, 8.9 fold, 4 fold, and 5.5 fold, respectively, on treatment with Noni as compared to untreated controls (p<0.05). In contrast, expression was found to be decreased 22 fold, 13 fold, 16 fold, and 23 fold on treatment with cisplatin (p<0.05). However, the combination of Noni and cisplatin led to an increase of 2 fold, 1.6 fold, 3 fold, 1.2 fold, respectively (p<0.05). Noni enhanced the expression of DNA repair genes by itself and in combination with cisplatin. However, high expression of DNA repair genes at mRNA level only signifies efficient DNA transcription of the above mentioned genes; further investigations are needed to evaluate the DNA repair protein expression.

Dynamics of folding: Impact of fault bend folds on earthquake cycles

NASA Astrophysics Data System (ADS)

Sathiakumar, S.; Barbot, S.; Hubbard, J.

2017-12-01

Earthquakes in subduction zones and subaerial convergent margins are some of the largest in the world. So far, forecasts of future earthquakes have primarily relied on assessing past earthquakes to look for seismic gaps and slip deficits. However, the roles of fault geometry and off-fault plasticity are typically overlooked. We use structural geology (fault-bend folding theory) to inform fault modeling in order to better understand how deformation is accommodated on the geological time scale and through the earthquake cycle. Fault bends in megathrusts, like those proposed for the Nepal Himalaya, will induce folding of the upper plate. This introduces changes in the slip rate on different fault segments, and therefore on the loading rate at the plate interface, profoundly affecting the pattern of earthquake cycles. We develop numerical simulations of slip evolution under rate-and-state friction and show that this effect introduces segmentation of the earthquake cycle. In crustal dynamics, it is challenging to describe the dynamics of fault-bend folds, because the deformation is accommodated by small amounts of slip parallel to bedding planes ("flexural slip"), localized on axial surface, i.e. folding axes pinned to fault bends. We use dislocation theory to describe the dynamics of folding along these axial surfaces, using analytic solutions that provide displacement and stress kernels to simulate the temporal evolution of folding and assess the effects of folding on earthquake cycles. Studies of the 2015 Gorkha earthquake, Nepal, have shown that fault geometry can affect earthquake segmentation. Here, we show that in addition to the fault geometry, the actual geology of the rocks in the hanging wall of the fault also affect critical parameters, including the loading rate on parts of the fault, based on fault-bend folding theory. Because loading velocity controls the recurrence time of earthquakes, these two effects together are likely to have a strong impact on the earthquake cycle.

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.

[Application of transcription mediated amplification and real-time reverse transcription polymerase chain reaction in detection of human immunodeficiency virus RNA].

PubMed

Wu, Daxian; Tao, Shuhui; Liu, Shuiping; Zhou, Jiebin; Tan, Deming; Hou, Zhouhua

2017-07-28

To observe the sensitivity of transcription mediated amplification (TMA), and to compare its performance with real-time reverse transcription polymerase chain reaction (real-time RT-PCR) in detecting human immunodeficiency virus RNA (HIV RNA).
 Methods: TMA system was established with TaqMan probes, specific primers, moloney murine leukemia virus (MMLV) reverse transcriptase, T7 RNA polymerase, and reaction substrates. The sensitivity of TMA was evaluated by amplifying a group of 10-fold diluted HIV RNA standards which were transcribed in vitro. A total of 60 plasma of HIV infected patients were measured by TMA and Cobas Amplicor HIV-1 Monitor test to observe the positive rate. The correlation and concordance of the above two technologies were investigated by linear regression and Bland-Altman analysis.
 Results: TMA system was established successfully and HIV RNA transcribed standards at concentration of equal or more than 10 copies/mL could be detected by TMA technology. Among 60 samples of plasma from HIV infected patients, 46 were positively detected and 12 were negatively amplified by both TMA and Cobas reagents; 2 samples were positively tested by Cobas reagent but negatively tested by TMA system. The concordance rate of the two methods was 97.1% and the difference of positive detection rate between the two methods was not statistically significant (P>0.05). Linear regression was used for 46 samples which were positively detected by both TMA and Cobas reagents and showed an excellent correlation between the two reagents (r=0.997, P<0.001). Bland-Altma analysis revealed that the mean different value of HIV RNA levels for denary logarithm was 0.02. Forty-four samples were included in 95% of credibility interval of concordance.
 Conclusion: TMA system has the potential of high sensitivity. TMA and real-time RT-PCR keep an excellent correlation and consistency in detecting HIV RNA.

Dark and bright solitons for the two-dimensional complex modified Korteweg-de Vries and Maxwell-Bloch system with time-dependent coefficient

NASA Astrophysics Data System (ADS)

Shaikhova, G.; Ozat, N.; Yesmakhanova, K.; Bekova, G.

2018-02-01

In this work, we present Lax pair for two-dimensional complex modified Korteweg-de Vries and Maxwell-Bloch (cmKdV-MB) system with the time-dependent coefficient. Dark and bright soliton solutions for the cmKdV-MB system with variable coefficient are received by Darboux transformation. Moreover, the determinant representation of the one-fold and two-fold Darboux transformation for the cmKdV-MB system with time-dependent coefficient is presented.

The Role of Blood Osmolality and Volume in Regulating Vasopressin Secretion in the Rat

PubMed Central

Dunn, Fredrick L.; Brennan, Thomas J.; Nelson, Averial E.; Robertson, Gary L.

1973-01-01

A sensitive and specific radioimmunoassay for plasma arginine vasopressin (AVP) has been used to study the effects of blood osmolality and volume in regulating AVP secretion in unanesthetized rats. Under basal conditions, plasma AVP and osmolality were relatively constant, averaging 2.3±0.9 (SD) pg/ml and 294±1.4 mosmol/kg, respectively. Fluid restriction, which increased osmolality and decreased volume, resulted in a progressive rise in plasma AVP to about 10 times basal levels after 96 h. A 2-3-fold increase in plasma AVP occurred as early as 12 h, when osmolality and volume had each changed by less than 2%. Intraperitoneal injections of hypertonic saline, which had no effect on blood volume, also produced a rise in plasma AVP that was linearly correlated with the rise in osmolality (r > 0.9) and quantitatively similar to that found during fluid restriction (plasma AVP increased 2-4-fold with each 1% increase in osmolality). Intraperitoneal injection of polyethylene glycol, which decreased blood volume without altering osmolality, also increased plasma AVP but this response followed an exponential pattern and did not become significant until volume had decreased by 8% or more. At these levels of hypovolemia, the osmoregulatory system continued to function but showed a lower threshold and increase sensitivity to osmotic stimulation. We conclude that AVP secretion is regulated principally by blood osmolality but that the responsiveness of this mechanism may be significantly altered by modest changes in blood volume. PMID:4750450

Inferring internal properties of Earth's core dynamics and their evolution from surface observations and a numerical geodynamo model

NASA Astrophysics Data System (ADS)

Aubert, J.; Fournier, A.

2011-10-01

Over the past decades, direct three-dimensional numerical modelling has been successfully used to reproduce the main features of the geodynamo. Here we report on efforts to solve the associated inverse problem, aiming at inferring the underlying properties of the system from the sole knowledge of surface observations and the first principle dynamical equations describing the convective dynamo. To this end we rely on twin experiments. A reference model time sequence is first produced and used to generate synthetic data, restricted here to the large-scale component of the magnetic field and its rate of change at the outer boundary. Starting from a different initial condition, a second sequence is next run and attempts are made to recover the internal magnetic, velocity and buoyancy anomaly fields from the sparse surficial data. In order to reduce the vast underdetermination of this problem, we use stochastic inversion, a linear estimation method determining the most likely internal state compatible with the observations and some prior knowledge, and we also implement a sequential evolution algorithm in order to invert time-dependent surface observations. The prior is the multivariate statistics of the numerical model, which are directly computed from a large number of snapshots stored during a preliminary direct run. The statistics display strong correlation between different harmonic degrees of the surface observations and internal fields, provided they share the same harmonic order, a natural consequence of the linear coupling of the governing dynamical equations and of the leading influence of the Coriolis force. Synthetic experiments performed with a weakly nonlinear model yield an excellent quantitative retrieval of the internal structure. In contrast, the use of a strongly nonlinear (and more realistic) model results in less accurate static estimations, which in turn fail to constrain the unobserved small scales in the time integration of the evolution scheme. Evaluating the quality of forecasts of the system evolution against the reference solution, we show that our scheme can improve predictions based on linear extrapolations on forecast horizons shorter than the system e-folding time. Still, in the perspective of forthcoming data assimilation activities, our study underlines the need of advanced estimation techniques able to cope with the moderate to strong nonlinearities present in the geodynamo.

[Case-control survey on risk factors of benign vocal fold lesions].

PubMed

Huang, Dong-Yan; Yang, Wei-Yan; Yu, Ping; He, Yao; Han, Dong-Yi

2008-02-01

To investigate the risk factors that may relate with benign vocal fold lesions including vocal fold nodule, vocal fold polyp, chronic laryngitis and Reinke's edema In present series, 321 cases who were performed laryngoscope were invited to participate the survey. Among them 168 cases with benign vocal fold lesions composed the case group. Another 153 cases with normal larynx composed the control group. Each case were undertook the same questionnaire. Logistic regression analysis was preformed to investigate the possible risk factors. The result demonstrated the occurring of benign vocal fold lesions positively correlated to five factors, including occupation, work or residence environment noise, alcohol-consuming, voice-using hours per day and abuse of voice. Occupations with intensive voice-use were more vulnerable to developing these disorders. Occurring risk of occupations type II with moderate voice-use was 1.934 times than that of occupations type I with lesser voice-use (OR = 1.934). And risk of occupations type III with upper voice-use was 2.633 times than that of type I. Risk raised 1.302 times with each more hour of voice use per day. OR of the following factors of voice abuse, environment noise, alcohol-consuming was 4.744, 2.115 and 2.177, respectively. The result suggested that people should abstain from alcohol, lowering the environment noise, prevent overuse and abuse of voice in order to decrease the prevalence of these disorders, which is especially important for the professional voice users, e. g. teachers or managers. The essential therapy for these disorders is to correct bad phonation habits.

A century of changing flows: Forest management changed flow magnitudes and warming advanced the timing of flow in a southwestern US river

PubMed Central

2017-01-01

The continued provision of water from rivers in the southwestern United States to downstream cities, natural communities and species is at risk due to higher temperatures and drought conditions in recent decades. Snowpack and snowfall levels have declined, snowmelt and peak spring flows are arriving earlier, and summer flows have declined. Concurrent to climate change and variation, a century of fire suppression has resulted in dramatic changes to forest conditions, and yet, few studies have focused on determining the degree to which changing forests have altered flows. In this study, we evaluated changes in flow, climate, and forest conditions in the Salt River in central Arizona from 1914–2012 to compare and evaluate the effects of changing forest conditions and temperatures on flows. After using linear regression models to remove the influence of precipitation and temperature, we estimated that annual flows declined by 8–29% from 1914–1963, coincident with a 2-fold increase in basal area, a 2-3-fold increase in canopy cover, and at least a 10-fold increase in forest density within ponderosa pine forests. Streamflow volumes declined by 37–56% in summer and fall months during this period. Declines in climate-adjusted flows reversed at mid-century when spring and annual flows increased by 10–31% from 1964–2012, perhaps due to more winter rainfall. Additionally, peak spring flows occurred about 12 days earlier in this period than in the previous period, coincident with winter and spring temperatures that increased by 1–2°C. While uncertainties remain, this study adds to the knowledge gained in other regions that forest change has had effects on flow that were on par with climate variability and, in the case of mid-century declines, well before the influence of anthropogenic warming. Current large-scale forest restoration projects hold some promise of recovering seasonal flows. PMID:29176868

High-throughput quantification for a drug mixture in rat plasma-a comparison of Ultra Performance liquid chromatography/tandem mass spectrometry with high-performance liquid chromatography/tandem mass spectrometry.

PubMed

Yu, Kate; Little, David; Plumb, Rob; Smith, Brian

2006-01-01

A quantitative Ultra Performance liquid chromatography/tandem mass spectrometry (UPL/MS/MS) protocol was developed for a five-compound mixture in rat plasma. A similar high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) quantification protocol was developed for comparison purposes. Among the five test compounds, three preferred positive electrospray ionization (ESI) and two preferred negative ESI. As a result, both UPLC/MS/MS and HPLC/MS/MS analyses were performed by having the mass spectrometer collecting ESI multiple reaction monitoring (MRM) data in both positive and negative ion modes during a single injection. Peak widths for most standards were 4.8 s for the HPLC analysis and 2.4 s for the UPLC analysis. There were 17 to 20 data points obtained for each of the LC peaks. Compared with the HPLC/MS/MS method, the UPLC/MS/MS method offered 3-fold decrease in retention time, up to 10-fold increase in detected peak height, with 2-fold decrease in peak width. Limits of quantification (LOQs) for both HPLC and UPLC methods were evaluated. For UPLC/MS/MS analysis, a linear range up to four orders of magnitude was obtained with r2 values ranging from 0.991 to 0.998. The LOQs for the five analytes ranged from 0.08 to 9.85 ng/mL. Three levels of quality control (QC) samples were analyzed. For the UPLC/MS/MS protocol, the percent relative standard deviation (RSD%) for low QC (2 ng/mL) ranged from 3.42 to 8.67% (N = 18). The carryover of the UPLC/MS/MS protocol was negligible and the robustness of the UPLC/MS/MS system was evaluated with up to 963 QC injections. Copyright 2006 John Wiley & Sons, Ltd.

Impact of Peptide Transporter 1 on the Intestinal Absorption and Pharmacokinetics of Valacyclovir after Oral Dose Escalation in Wild-Type and PepT1 Knockout Mice

PubMed Central

Yang, Bei; Hu, Yongjun

2013-01-01

The primary objective of this study was to determine the in vivo absorption properties of valacyclovir, including the potential for saturable proton-coupled oligopeptide transporter 1 (PepT1)-mediated intestinal uptake, after escalating oral doses of prodrug within the clinical dose range. A secondary aim was to characterize the role of PepT1 on the tissue distribution of its active metabolite, acyclovir. [3H]Valacyclovir was administered to wild-type (WT) and PepT1 knockout (KO) mice by oral gavage at doses of 10, 25, 50, and 100 nmol/g. Serial blood samples were collected over 180 minutes, and tissue distribution studies were performed 20 minutes after a 25-nmol/g oral dose of valacyclovir. We found that the Cmax and area under the curve (AUC)0–180 of acyclovir were 4- to 6-fold and 2- to 3-fold lower, respectively, in KO mice for all four oral doses of valacyclovir. The time to peak concentration of acyclovir was 3- to 10-fold longer in KO compared with WT mice. There was dose proportionality in the Cmax and AUC0–180 of acyclovir in WT and KO mice over the valacyclovir oral dose range of 10–100 nmol/g (i.e., linear absorption kinetics). No differences were observed in the peripheral tissue distribution of acyclovir once these tissues were adjusted for differences in perfusing drug concentrations in the systemic circulation. In contrast, some differences were observed between genotypes in the concentrations of acyclovir in the distal intestine. Collectively, the findings demonstrate a critical role of intestinal PepT1 in improving the rate and extent of oral absorption for valacyclovir. Moreover, this study provides definitive evidence for the rational development of a PepT1-targeted prodrug strategy. PMID:23924683

New force replica exchange method and protein folding pathways probed by force-clamp technique.

PubMed

Kouza, Maksim; Hu, Chin-Kun; Li, Mai Suan

2008-01-28

We have developed a new extended replica exchange method to study thermodynamics of a system in the presence of external force. Our idea is based on the exchange between different force replicas to accelerate the equilibrium process. This new approach was applied to obtain the force-temperature phase diagram and other thermodynamical quantities of the three-domain ubiquitin. Using the C(alpha)-Go model and the Langevin dynamics, we have shown that the refolding pathways of single ubiquitin depend on which terminus is fixed. If the N end is fixed then the folding pathways are different compared to the case when both termini are free, but fixing the C terminal does not change them. Surprisingly, we have found that the anchoring terminal does not affect the pathways of individual secondary structures of three-domain ubiquitin, indicating the important role of the multidomain construction. Therefore, force-clamp experiments, in which one end of a protein is kept fixed, can probe the refolding pathways of a single free-end ubiquitin if one uses either the polyubiquitin or a single domain with the C terminus anchored. However, it is shown that anchoring one end does not affect refolding pathways of the titin domain I27, and the force-clamp spectroscopy is always capable to predict folding sequencing of this protein. We have obtained the reasonable estimate for unfolding barrier of ubiquitin, using the microscopic theory for the dependence of unfolding time on the external force. The linkage between residue Lys48 and the C terminal of ubiquitin is found to have the dramatic effect on the location of the transition state along the end-to-end distance reaction coordinate, but the multidomain construction leaves the transition state almost unchanged. We have found that the maximum force in the force-extension profile from constant velocity force pulling simulations depends on temperature nonlinearly. However, for some narrow temperature interval this dependence becomes linear, as have been observed in recent experiments.

In vitro and in vivo characterization of a dual-function green fluorescent protein--HSV1-thymidine kinase reporter gene driven by the human elongation factor 1 alpha promoter.

PubMed

Luker, Gary D; Luker, Kathryn E; Sharma, Vijay; Pica, Christina M; Dahlheimer, Julie L; Ocheskey, Joe A; Fahrner, Timothy J; Milbrandt, Jeffrey; Piwnica-Worms, David

2002-01-01

Toward the goal of monitoring activity of native mammalian promoters with molecular imaging techniques, we stably transfected DU145 prostate carcinoma cells with a fusion construct of enhanced green fluorescent protein (EGFP) and wild-type herpes simplex virus-1 thymidine kinase (HSV1-TK) as a reporter gene driven by the promoter for human elongation factor 1 alpha (EF-1 alpha-EGFP-TK). Using this model system, expression of EGFP was quantified by flow cytometry and fluorescence microscopy, while the HSV1-TK component of the reporter was quantified with 8-[3H]ganciclovir (8-[3H]GCV). As analyzed by flow cytometry, passage of EGFP-TK-DU145 transfected cells (ETK) in vitro resulted in populations of cells with high and low expression of EGFP over time. High and low ETK cells retained 23-fold and 5-fold more GCV, respectively, than control. While differences in uptake and retention of GCV corresponded to relative expression of the reporter gene in each subpopulation of cells as determined by both flow cytometry (EGFP) and quantitative RT-PCR, the correlation was not linear. Furthermore, in high ETK cells, net retention of various radiolabeled nucleoside analogues varied; the rank order was 8-[3H]GCV < 9-(4-fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG) approximately 8-[3H]penciclovir (8-[3H]PCV) < 2'-fluoro-2'-deoxy-5-iodouracil-beta-D-arabinofuranoside (2-[14C]FIAU). Xenograft tumors of ETK cells in vivo accumulated 2.5-fold more 8-[3H]GCV per gram of tissue and showed greater fluorescence from EGFP than control DU145 cells, demonstrating that the reporter gene functioned in vivo. These data extend previous reports by showing that a human promoter can be detected in vitro and in vivo with a dual-function reporter exploiting optical and radiotracer techniques.

Mercury in the soil of two contrasting watersheds in the eastern United States

USGS Publications Warehouse

Burns, Douglas A.; Woodruff, Laurel G.; Bradley, Paul M.; Cannon, William F.

2014-01-01

Soil represents the largest store of mercury (Hg) in terrestrial ecosystems, and further study of the factors associated with soil Hg storage is needed to address concerns about the magnitude and persistence of global environmental Hg bioaccumulation. To address this need, we compared total Hg and methyl Hg concentrations and stores in the soil of different landscapes in two watersheds in different geographic settings with similar and relatively high methyl Hg concentrations in surface waters and biota, Fishing Brook, Adirondack Mountains, New York, and McTier Creek, Coastal Plain, South Carolina. Median total Hg concentrations and stores in organic and mineral soil samples were three-fold greater at Fishing Brook than at McTier Creek. Similarly, median methyl Hg concentrations were about two-fold greater in Fishing Brook soil than in McTier Creek soil, but this difference was significant only for mineral soil samples, and methyl Hg stores were not significantly different among these watersheds. In contrast, the methyl Hg/total Hg ratio was significantly greater at McTier Creek suggesting greater climate-driven methylation efficiency in the Coastal Plain soil than that of the Adirondack Mountains. The Adirondack soil had eight-fold greater soil organic matter than that of the Coastal Plain, consistent with greater total Hg stores in the northern soil, but soil organic matter – total Hg relations differed among the sites. A strong linear relation was evident at McTier Creek (r2 = 0.68; p2 = 0.13; p<0.001) and highly variable across the soil organic matter content range, suggesting excess Hg binding capacity in the Adirondack soil. These results suggest greater total Hg turnover time in Adirondack soil than that of the Coastal Plain, and that future declines in stream water Hg concentrations driven by declines in atmospheric Hg deposition will be more gradual and prolonged in the Adirondacks.

Adipose tissue content and distribution in children and adolescents with bronchial asthma.

PubMed

Umławska, Wioleta

2015-02-01

The excess of adipose tissue and the pattern of adipose tissue distribution in the body seem to play an important role in the complicated dependencies between obesity and risk of developing asthma. The aim of the present study was to determine nutritional status in children and adolescents with bronchial asthma with special emphasis on adipose tissue distribution evaluated on the basis of skin-fold thicknesses, and to determine the relationships between patterns of adipose tissue distribution and the course of the disease. Anthropometric data on height, weight, circumferences and skin-fold thicknesses were extracted from the medical histories of 261 children diagnosed with asthma bronchitis. Values for children with asthma were compared to Polish national growth reference charts. Distribution of subcutaneous adipose tissue was evaluated using principal components analysis (PCA). Multivariate linear regression analyses tested the effect of three factors on subcutaneous adipose tissue distribution: type of asthma, the severity of the disease and the duration of the disease. Mean body height in the children examined in this study was lower than in their healthy peers. Mean BMI and skin-fold thicknesses were significantly higher and lean body mass was lower in the study group. Excess body fat was noted, especially in girls. Adipose tissue was preferentially deposited in the trunk in girls with severe asthma, as well as in those who had been suffering from asthma for a longer time. The type of asthma, atopic or non-atopic, had no observable effect on subcutaneous adipose tissue distribution in children examined. The data suggest that long-treated subjects and those with severe bronchial asthma accumulate more adipose tissue on the trunk. It is important to regularly monitor nutritional status in children with asthma, especially in those receiving high doses of systemic or inhaled glucocorticosteroids, and long-term treatment as well. Copyright © 2014 Elsevier Ltd. All rights reserved.

Energy landscape of knotted protein folding

PubMed Central

Sułkowska, Joanna I.; Noel, Jeffrey K.; Onuchic, Jose N.

2012-01-01

Recent experiments have conclusively shown that proteins are able to fold from an unknotted, denatured polypeptide to the knotted, native state without the aid of chaperones. These experiments are consistent with a growing body of theoretical work showing that a funneled, minimally frustrated energy landscape is sufficient to fold small proteins with complex topologies. Here, we present a theoretical investigation of the folding of a knotted protein, 2ouf, engineered in the laboratory by a domain fusion that mimics an evolutionary pathway for knotted proteins. Unlike a previously studied knotted protein of similar length, we see reversible folding/knotting and a surprising lack of deep topological traps with a coarse-grained structure-based model. Our main interest is to investigate how evolution might further select the geometry and stiffness of the threading region of the newly fused protein. We compare the folding of the wild-type protein to several mutants. Similarly to the wild-type protein, all mutants show robust and reversible folding, and knotting coincides with the transition state ensemble. As observed experimentally, our simulations show that the knotted protein folds about ten times slower than an unknotted construct with an identical contact map. Simulated folding kinetics reflect the experimentally observed rollover in the folding limbs of chevron plots. Successful folding of the knotted protein is restricted to a narrow range of temperature as compared to the unknotted protein and fits of the kinetic folding data below folding temperature suggest slow, nondiffusive dynamics for the knotted protein. PMID:22891304

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.

The effect of vocal fold vertical stiffness gradient on sound production

NASA Astrophysics Data System (ADS)

Geng, Biao; Xue, Qian; Zheng, Xudong

2015-11-01

It is observed in some experimental studies on canine vocal folds (VFs) that the inferior aspect of the vocal fold (VF) is much stiffer than the superior aspect under relatively large strain. Such vertical difference is supposed to promote the convergent-divergent shape during VF vibration and consequently facilitate the production of sound. In this study, we investigate the effect of vertical variation of VF stiffness on sound production using a numerical model. The vertical variation of stiffness is produced by linearly increasing the Young's modulus and shear modulus from the superior to inferior aspects in the cover layer, and its effect on phonation is examined in terms of aerodynamic and acoustic quantities such as flow rate, open quotient, skewness of flow wave form, sound intensity and vocal efficiency. The flow-induced vibration of the VF is solved with a finite element solver coupled with 1D Bernoulli equation, which is further coupled with a digital waveguide model. This study is designed to find out whether it's beneficial to artificially induce the vertical stiffness gradient by certain implanting material in VF restoring surgery, and if it is beneficial, what gradient is the most favorable.

Relative stability of major types of beta-turns as a function of amino acid composition: a study based on Ab initio energetic and natural abundance data.

PubMed

Perczel, András; Jákli, Imre; McAllister, Michael A; Csizmadia, Imre G

2003-06-06

Folding properties of small globular proteins are determined by their amino acid sequence (primary structure). This holds both for local (secondary structure) and for global conformational features of linear polypeptides and proteins composed from natural amino acid derivatives. It thus provides the rational basis of structure prediction algorithms. The shortest secondary structure element, the beta-turn, most typically adopts either a type I or a type II form, depending on the amino acid composition. Herein we investigate the sequence-dependent folding stability of both major types of beta-turns using simple dipeptide models (-Xxx-Yyy-). Gas-phase ab initio properties of 16 carefully selected and suitably protected dipeptide models (for example Val-Ser, Ala-Gly, Ser-Ser) were studied. For each backbone fold most probable side-chain conformers were considered. Fully optimized 321G RHF molecular structures were employed in medium level [B3LYP/6-311++G(d,p)//RHF/3-21G] energy calculations to estimate relative populations of the different backbone conformers. Our results show that the preference for beta-turn forms as calculated by quantum mechanics and observed in Xray determined proteins correlates significantly.

Characterization of the seismically imaged Tuscarora fold system and implications for layer parallel shortening in the Pennsylvania salient

NASA Astrophysics Data System (ADS)

Mount, Van S.; Wilkins, Scott; Comiskey, Cody S.

2017-12-01

The Tuscarora fold system (TFS) is located in the Pennsylvania salient in the foreland of the Valley and Ridge province. The TFS is imaged in high quality 3D seismic data and comprises a system of small-scale folds within relatively flat-lying Lower Silurian Tuscarora Formation strata. We characterize the TFS structures and infer layer parallel shortening (LPS) directions and magnitudes associated with deformation during the Alleghany Orogeny. Previously reported LPS data in our study area are from shallow Devonian and Carboniferous strata (based on outcrop and core analyses) above the shallowest of three major detachments recognized in the region. Seismic data allows us to characterize LPS at depth in strata beneath the shallow detachment. Our LPS data (orientations and inferred magnitudes) are consistent with the shallow data leading us to surmise that LPS during Alleghanian deformation fanned around the salient and was distributed throughout the stratigraphic section - and not isolated to strata above the shallow detachment. We propose that a NW-SE oriented Alleghanian maximum principal stress was perturbed by deep structure associated with the non-linear margin of Laurentia resulting in fanning of shortening directions within the salient.

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

Origami tubes with reconfigurable polygonal cross-sections.

PubMed

Filipov, E T; Paulino, G H; Tachi, T

2016-01-01

Thin sheets can be assembled into origami tubes to create a variety of deployable, reconfigurable and mechanistically unique three-dimensional structures. We introduce and explore origami tubes with polygonal, translational symmetric cross-sections that can reconfigure into numerous geometries. The tubular structures satisfy the mathematical definitions for flat and rigid foldability, meaning that they can fully unfold from a flattened state with deformations occurring only at the fold lines. The tubes do not need to be straight and can be constructed to follow a non-linear curved line when deployed. The cross-section and kinematics of the tubular structures can be reprogrammed by changing the direction of folding at some folds. We discuss the variety of tubular structures that can be conceived and we show limitations that govern the geometric design. We quantify the global stiffness of the origami tubes through eigenvalue and structural analyses and highlight the mechanical characteristics of these systems. The two-scale nature of this work indicates that, from a local viewpoint, the cross-sections of the polygonal tubes are reconfigurable while, from a global viewpoint, deployable tubes of desired shapes are achieved. This class of tubes has potential applications ranging from pipes and micro-robotics to deployable architecture in buildings.

Origami tubes with reconfigurable polygonal cross-sections

PubMed Central

Filipov, E. T.; Paulino, G. H.; Tachi, T.

2016-01-01

Thin sheets can be assembled into origami tubes to create a variety of deployable, reconfigurable and mechanistically unique three-dimensional structures. We introduce and explore origami tubes with polygonal, translational symmetric cross-sections that can reconfigure into numerous geometries. The tubular structures satisfy the mathematical definitions for flat and rigid foldability, meaning that they can fully unfold from a flattened state with deformations occurring only at the fold lines. The tubes do not need to be straight and can be constructed to follow a non-linear curved line when deployed. The cross-section and kinematics of the tubular structures can be reprogrammed by changing the direction of folding at some folds. We discuss the variety of tubular structures that can be conceived and we show limitations that govern the geometric design. We quantify the global stiffness of the origami tubes through eigenvalue and structural analyses and highlight the mechanical characteristics of these systems. The two-scale nature of this work indicates that, from a local viewpoint, the cross-sections of the polygonal tubes are reconfigurable while, from a global viewpoint, deployable tubes of desired shapes are achieved. This class of tubes has potential applications ranging from pipes and micro-robotics to deployable architecture in buildings. PMID:26997894

The E. coli thioredoxin folding mechanism: the key role of the C-terminal helix.

PubMed

Vazquez, Diego S; Sánchez, Ignacio E; Garrote, Ana; Sica, Mauricio P; Santos, Javier

2015-02-01

In this work, the unfolding mechanism of oxidized Escherichia coli thioredoxin (EcTRX) was investigated experimentally and computationally. We characterized seven point mutants distributed along the C-terminal α-helix (CTH) and the preceding loop. The mutations destabilized the protein against global unfolding while leaving the native structure unchanged. Global analysis of the unfolding kinetics of all variants revealed a linear unfolding route with a high-energy on-pathway intermediate state flanked by two transition state ensembles TSE1 and TSE2. The experiments show that CTH is mainly unfolded in TSE1 and the intermediate and becomes structured in TSE2. Structure-based molecular dynamics are in agreement with these experiments and provide protein-wide structural information on transient states. In our model, EcTRX folding starts with structure formation in the β-sheet, while the protein helices coalesce later. As a whole, our results indicate that the CTH is a critical module in the folding process, restraining a heterogeneous intermediate ensemble into a biologically active native state and providing the native protein with thermodynamic and kinetic stability. Copyright © 2014 Elsevier B.V. All rights reserved.