Translational regulation of ribosomal protein S15 drives characteristic patterns of protein-mRNA epistasis.

PubMed

Mallik, Saurav; Basu, Sudipto; Hait, Suman; Kundu, Sudip

2018-04-21

Do coding and regulatory segments of a gene co-evolve with each-other? Seeking answers to this question, here we analyze the case of Escherichia coli ribosomal protein S15, that represses its own translation by specifically binding its messenger RNA (rpsO mRNA) and stabilizing a pseudoknot structure at the upstream untranslated region, thus trapping the ribosome into an incomplete translation initiation complex. In the absence of S15, ribosomal protein S1 recognizes rpsO and promotes translation by melting this very pseudoknot. We employ a robust statistical method to detect signatures of positive epistasis between residue site pairs and find that biophysical constraints of translational regulation (S15-rpsO and S1-rpsO recognition, S15-mediated rpsO structural rearrangement, and S1-mediated melting) are strong predictors of positive epistasis. Transforming the epistatic pairs into a network, we find that signatures of two different, but interconnected regulatory cascades are imprinted in the sequence-space and can be captured in terms of two dense network modules that are sparsely connected to each other. This network topology further reflects a general principle of how functionally coupled components of biological networks are interconnected. These results depict a model case, where translational regulation drives characteristic residue-level epistasis-not only between a protein and its own mRNA but also between a protein and the mRNA of an entirely different protein. © 2018 Wiley Periodicals, Inc.

Classification of Complete Proteomes of Different Organisms and Protein Sets Based on Their Protein Distributions in Terms of Some Key Attributes of Proteins

DOE PAGES

Guo, Hao-Bo; Ma, Yue; Tuskan, Gerald A.; ...

2018-01-01

The existence of complete genome sequences makes it important to develop different approaches for classification of large-scale data sets and to make extraction of biological insights easier. Here, we propose an approach for classification of complete proteomes/protein sets based on protein distributions on some basic attributes. We demonstrate the usefulness of this approach by determining protein distributions in terms of two attributes: protein lengths and protein intrinsic disorder contents (ID). The protein distributions based on L and ID are surveyed for representative proteome organisms and protein sets from the three domains of life. The two-dimensional maps (designated as fingerprints here)more » from the protein distribution densities in the LD space defined by ln( L ) and ID are then constructed. The fingerprints for different organisms and protein sets are found to be distinct with each other, and they can therefore be used for comparative studies. As a test case, phylogenetic trees have been constructed based on the protein distribution densities in the fingerprints of proteomes of organisms without performing any protein sequence comparison and alignments. The phylogenetic trees generated are biologically meaningful, demonstrating that the protein distributions in the LD space may serve as unique phylogenetic signals of the organisms at the proteome level.« less

Classification of Complete Proteomes of Different Organisms and Protein Sets Based on Their Protein Distributions in Terms of Some Key Attributes of Proteins

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

Guo, Hao-Bo; Ma, Yue; Tuskan, Gerald A.

The existence of complete genome sequences makes it important to develop different approaches for classification of large-scale data sets and to make extraction of biological insights easier. Here, we propose an approach for classification of complete proteomes/protein sets based on protein distributions on some basic attributes. We demonstrate the usefulness of this approach by determining protein distributions in terms of two attributes: protein lengths and protein intrinsic disorder contents (ID). The protein distributions based on L and ID are surveyed for representative proteome organisms and protein sets from the three domains of life. The two-dimensional maps (designated as fingerprints here)more » from the protein distribution densities in the LD space defined by ln( L ) and ID are then constructed. The fingerprints for different organisms and protein sets are found to be distinct with each other, and they can therefore be used for comparative studies. As a test case, phylogenetic trees have been constructed based on the protein distribution densities in the fingerprints of proteomes of organisms without performing any protein sequence comparison and alignments. The phylogenetic trees generated are biologically meaningful, demonstrating that the protein distributions in the LD space may serve as unique phylogenetic signals of the organisms at the proteome level.« less

Classification of Complete Proteomes of Different Organisms and Protein Sets Based on Their Protein Distributions in Terms of Some Key Attributes of Proteins

PubMed Central

Ma, Yue; Tuskan, Gerald A.

2018-01-01

The existence of complete genome sequences makes it important to develop different approaches for classification of large-scale data sets and to make extraction of biological insights easier. Here, we propose an approach for classification of complete proteomes/protein sets based on protein distributions on some basic attributes. We demonstrate the usefulness of this approach by determining protein distributions in terms of two attributes: protein lengths and protein intrinsic disorder contents (ID). The protein distributions based on L and ID are surveyed for representative proteome organisms and protein sets from the three domains of life. The two-dimensional maps (designated as fingerprints here) from the protein distribution densities in the LD space defined by ln(L) and ID are then constructed. The fingerprints for different organisms and protein sets are found to be distinct with each other, and they can therefore be used for comparative studies. As a test case, phylogenetic trees have been constructed based on the protein distribution densities in the fingerprints of proteomes of organisms without performing any protein sequence comparison and alignments. The phylogenetic trees generated are biologically meaningful, demonstrating that the protein distributions in the LD space may serve as unique phylogenetic signals of the organisms at the proteome level. PMID:29686995

On the Distribution of Protein Refractive Index Increments

PubMed Central

Zhao, Huaying; Brown, Patrick H.; Schuck, Peter

2011-01-01

The protein refractive index increment, dn/dc, is an important parameter underlying the concentration determination and the biophysical characterization of proteins and protein complexes in many techniques. In this study, we examine the widely used assumption that most proteins have dn/dc values in a very narrow range, and reappraise the prediction of dn/dc of unmodified proteins based on their amino acid composition. Applying this approach in large scale to the entire set of known and predicted human proteins, we obtain, for the first time, to our knowledge, an estimate of the full distribution of protein dn/dc values. The distribution is close to Gaussian with a mean of 0.190 ml/g (for unmodified proteins at 589 nm) and a standard deviation of 0.003 ml/g. However, small proteins <10 kDa exhibit a larger spread, and almost 3000 proteins have values deviating by more than two standard deviations from the mean. Due to the widespread availability of protein sequences and the potential for outliers, the compositional prediction should be convenient and provide greater accuracy than an average consensus value for all proteins. We discuss how this approach should be particularly valuable for certain protein classes where a high dn/dc is coincidental to structural features, or may be functionally relevant such as in proteins of the eye. PMID:21539801

On the distribution of protein refractive index increments.

PubMed

Zhao, Huaying; Brown, Patrick H; Schuck, Peter

2011-05-04

The protein refractive index increment, dn/dc, is an important parameter underlying the concentration determination and the biophysical characterization of proteins and protein complexes in many techniques. In this study, we examine the widely used assumption that most proteins have dn/dc values in a very narrow range, and reappraise the prediction of dn/dc of unmodified proteins based on their amino acid composition. Applying this approach in large scale to the entire set of known and predicted human proteins, we obtain, for the first time, to our knowledge, an estimate of the full distribution of protein dn/dc values. The distribution is close to Gaussian with a mean of 0.190 ml/g (for unmodified proteins at 589 nm) and a standard deviation of 0.003 ml/g. However, small proteins <10 kDa exhibit a larger spread, and almost 3000 proteins have values deviating by more than two standard deviations from the mean. Due to the widespread availability of protein sequences and the potential for outliers, the compositional prediction should be convenient and provide greater accuracy than an average consensus value for all proteins. We discuss how this approach should be particularly valuable for certain protein classes where a high dn/dc is coincidental to structural features, or may be functionally relevant such as in proteins of the eye. Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Current distribution in tissues with conducted electrical weapons operated in drive-stun mode.

PubMed

Panescu, Dorin; Kroll, Mark W; Brave, Michael

2016-08-01

The TASER® conducted electrical weapon (CEW) is best known for delivering electrical pulses that can temporarily incapacitate subjects by overriding normal motor control. The alternative drive-stun mode is less understood and the goal of this paper is to analyze the distribution of currents in tissues when the CEW is operated in this mode. Finite element modeling (FEM) was used to approximate current density in tissues with boundary electrical sources placed 40 mm apart. This separation was equivalent to the distance between drive-stun mode TASER X26™, X26P, X2 CEW electrodes located on the device itself and between those located on the expended CEW cartridge. The FEMs estimated the amount of current flowing through various body tissues located underneath the electrodes. The FEM simulated the attenuating effects of both a thin and of a normal layer of fat. The resulting current density distributions were used to compute the residual amount of current flowing through deeper layers of tissue. Numerical modeling estimated that the skin, fat and skeletal muscle layers passed at least 86% or 91% of total CEW current, assuming a thin or normal fat layer thickness, respectively. The current density and electric field strength only exceeded thresholds which have increased probability for ventricular fibrillation (VFTJ), or for cardiac capture (CCTE), in the skin and the subdermal fat layers. The fat layer provided significant attenuation of drive-stun CEW currents. Beyond the skeletal muscle layer, only fractional amounts of the total CEW current were estimated to flow. The regions presenting risk for VF induction or for cardiac capture were well away from the typical heart depth.

How the hydrophobic factor drives protein folding

PubMed Central

Baldwin, Robert L.; Rose, George D.

2016-01-01

How hydrophobicity (HY) drives protein folding is studied. The 1971 Nozaki–Tanford method of measuring HY is modified to use gases as solutes, not crystals, and this makes the method easy to use. Alkanes are found to be much more hydrophobic than rare gases, and the two different kinds of HY are termed intrinsic (rare gases) and extrinsic (alkanes). The HY values of rare gases are proportional to solvent-accessible surface area (ASA), whereas the HY values of alkanes depend on special hydration shells. Earlier work showed that hydration shells produce the hydration energetics of alkanes. Evidence is given here that the transfer energetics of alkanes to cyclohexane [Wolfenden R, Lewis CA, Jr, Yuan Y, Carter CW, Jr (2015) Proc Natl Acad Sci USA 112(24):7484–7488] measure the release of these shells. Alkane shells are stabilized importantly by van der Waals interactions between alkane carbon and water oxygen atoms. Thus, rare gases cannot form this type of shell. The very short (approximately picoseconds) lifetime of the van der Waals interaction probably explains why NMR efforts to detect alkane hydration shells have failed. The close similarity between the sizes of the opposing energetics for forming or releasing alkane shells confirms the presence of these shells on alkanes and supports Kauzmann's 1959 mechanism of protein folding. A space-filling model is given for the hydration shells on linear alkanes. The model reproduces the n values of Jorgensen et al. [Jorgensen WL, Gao J, Ravimohan C (1985) J Phys Chem 89:3470–3473] for the number of waters in alkane hydration shells. PMID:27791131

CARd-3D: Carbon Distribution in 3D Structure Program for Globular Proteins

PubMed Central

Ekambaram, Rajasekaran; Kannaiyan, Akila; Marimuthu, Vijayasarathy; Swaminathan, Vinobha Chinnaiah; Renganathan, Senthil; Perumal, Ananda Gopu

2014-01-01

Spatial arrangement of carbon in protein structure is analyzed here. Particularly, the carbon fractions around individual atoms are compared. It is hoped that it follows the principle of 31.45% carbon around individual atoms. The results reveal that globular protein's atoms follow this principle. A comparative study on monomer versus dimer reveal that carbon is better distributed in dimeric form than in its monomeric form. Similar study on solid versus liquid structures reveals that the liquid (NMR) structure has better carbon distribution over the corresponding solid (X-Ray) structure. The carbon fraction distributions in fiber and toxin protein are compared. Fiber proteins follow the principle of carbon fraction distribution. At the same time it has another broad spectrum of carbon distribution than in globular proteins. The toxin protein follows an abnormal carbon fraction distribution. The carbon fraction distribution plays an important role in deciding the structure and shape of proteins. It is hoped to help in understanding the protein folding and function. PMID:24748753

Protein folding: complex potential for the driving force in a two-dimensional space of collective variables.

PubMed

Chekmarev, Sergei F

2013-10-14

Using the Helmholtz decomposition of the vector field of folding fluxes in a two-dimensional space of collective variables, a potential of the driving force for protein folding is introduced. The potential has two components. One component is responsible for the source and sink of the folding flows, which represent respectively, the unfolded states and the native state of the protein, and the other, which accounts for the flow vorticity inherently generated at the periphery of the flow field, is responsible for the canalization of the flow between the source and sink. The theoretical consideration is illustrated by calculations for a model β-hairpin protein.

Fruit availability drives the distribution of a folivorous-frugivorous primate within a large forest remnant.

PubMed

Camaratta, Danielle; Chaves, Óscar M; Bicca-Marques, Júlio César

2017-03-01

Understanding the ecological factors that influence the presence, abundance, and distribution of species within their habitats is critical for ensuring their long-term conservation. In the case of primary consumers, such as most primates, the availability and richness of plant foods are considered key drivers of population density at these variables influence the spatial distribution of social units within a finer, habitat patch level scale. We tested the hypothesis that the spatiotemporal availability and richness of plant foods, drive the spatial distribution of brown howler monkeys (Alouatta guariba clamitans) at a fine spatial scale. We established five line transects (2.6-4.3 km long) to census the population of brown howlers in Morro São Pedro, a 1,200 ha Atlantic forest remnant in southern Brazil, every 2 weeks from January to June 2015. We used data from tree inventories performed in sighting and control plots, and phenological surveys of 17 top food tree species to estimate bi-weekly food availability. We recorded a total of 95 sightings. The number of sightings per sampling period ranged from 2 to 12. The availability of fruit (ripe and unripe) was higher in sighting than in control plots, whereas leaf availability and the richness of food tree species was similar. We conclude that the spatial distribution of fruiting trees and the availability of fruit drive the pattern of habitat use, and spacing of brown howler groups in Morro São Pedro. © 2017 Wiley Periodicals, Inc.

Distributed synchronization of networked drive-response systems: A nonlinear fixed-time protocol.

PubMed

Zhao, Wen; Liu, Gang; Ma, Xi; He, Bing; Dong, Yunfeng

2017-11-01

The distributed synchronization of networked drive-response systems is investigated in this paper. A novel nonlinear protocol is proposed to ensure that the tracking errors converge to zeros in a fixed-time. By comparison with previous synchronization methods, the present method considers more practical conditions and the synchronization time is not dependent of arbitrary initial conditions but can be offline pre-assign according to the task assignment. Finally, the feasibility and validity of the presented protocol have been illustrated by a numerical simulation. Copyright © 2017. Published by Elsevier Ltd.

Ensemble models of proteins and protein domains based on distance distribution restraints.

PubMed

Jeschke, Gunnar

2016-04-01

Conformational ensembles of intrinsically disordered peptide chains are not fully determined by experimental observations. Uncertainty due to lack of experimental restraints and due to intrinsic disorder can be distinguished if distance distributions restraints are available. Such restraints can be obtained from pulsed dipolar electron paramagnetic resonance (EPR) spectroscopy applied to pairs of spin labels. Here, we introduce a Monte Carlo approach for generating conformational ensembles that are consistent with a set of distance distribution restraints, backbone dihedral angle statistics in known protein structures, and optionally, secondary structure propensities or membrane immersion depths. The approach is tested with simulated restraints for a terminal and an internal loop and for a protein with 69 residues by using sets of sparse restraints for underlying well-defined conformations and for published ensembles of a premolten globule-like and a coil-like intrinsically disordered protein. © 2016 Wiley Periodicals, Inc.

Amino Acid Distribution Rules Predict Protein Fold: Protein Grammar for Beta-Strand Sandwich-Like Structures

PubMed Central

Kister, Alexander

2015-01-01

We present an alternative approach to protein 3D folding prediction based on determination of rules that specify distribution of “favorable” residues, that are mainly responsible for a given fold formation, and “unfavorable” residues, that are incompatible with that fold, in polypeptide sequences. The process of determining favorable and unfavorable residues is iterative. The starting assumptions are based on the general principles of protein structure formation as well as structural features peculiar to a protein fold under investigation. The initial assumptions are tested one-by-one for a set of all known proteins with a given structure. The assumption is accepted as a “rule of amino acid distribution” for the protein fold if it holds true for all, or near all, structures. If the assumption is not accepted as a rule, it can be modified to better fit the data and then tested again in the next step of the iterative search algorithm, or rejected. We determined the set of amino acid distribution rules for a large group of beta sandwich-like proteins characterized by a specific arrangement of strands in two beta sheets. It was shown that this set of rules is highly sensitive (~90%) and very specific (~99%) for identifying sequences of proteins with specified beta sandwich fold structure. The advantage of the proposed approach is that it does not require that query proteins have a high degree of homology to proteins with known structure. So long as the query protein satisfies residue distribution rules, it can be confidently assigned to its respective protein fold. Another advantage of our approach is that it allows for a better understanding of which residues play an essential role in protein fold formation. It may, therefore, facilitate rational protein engineering design. PMID:25625198

Physical driving force of actomyosin motility based on the hydration effect.

PubMed

Suzuki, Makoto; Mogami, George; Ohsugi, Hideyuki; Watanabe, Takahiro; Matubayasi, Nobuyuki

2017-12-01

We propose a driving force hypothesis based on previous thermodynamics, kinetics and structural data as well as additional experiments and calculations presented here on water-related phenomena in the actomyosin systems. Although Szent-Györgyi pointed out the importance of water in muscle contraction in 1951, few studies have focused on the water science of muscle because of the difficulty of analyzing hydration properties of the muscle proteins, actin, and myosin. The thermodynamics and energetics of muscle contraction are linked to the water-mediated regulation of protein-ligand and protein-protein interactions along with structural changes in protein molecules. In this study, we assume the following two points: (1) the periodic electric field distribution along an actin filament (F-actin) is unidirectionally modified upon binding of myosin subfragment 1 (M or myosin S1) with ADP and inorganic phosphate Pi (M.ADP.Pi complex) and (2) the solvation free energy of myosin S1 depends on the external electric field strength and the solvation free energy of myosin S1 in close proximity to F-actin can become the potential force to drive myosin S1 along F-actin. The first assumption is supported by integration of experimental reports. The second assumption is supported by model calculations utilizing molecular dynamics (MD) simulation to determine solvation free energies of a small organic molecule and two small proteins. MD simulations utilize the energy representation method (ER) and the roughly proportional relationship between the solvation free energy and the solvent-accessible surface area (SASA) of the protein. The estimated driving force acting on myosin S1 is as high as several piconewtons (pN), which is consistent with the experimentally observed force. © 2017 Wiley Periodicals, Inc.

Finite-time hybrid projective synchronization of the drive-response complex networks with distributed-delay via adaptive intermittent control

NASA Astrophysics Data System (ADS)

Cheng, Lin; Yang, Yongqing; Li, Li; Sui, Xin

2018-06-01

This paper studies the finite-time hybrid projective synchronization of the drive-response complex networks. In the model, general transmission delays and distributed delays are also considered. By designing the adaptive intermittent controllers, the response network can achieve hybrid projective synchronization with the drive system in finite time. Based on finite-time stability theory and several differential inequalities, some simple finite-time hybrid projective synchronization criteria are derived. Two numerical examples are given to illustrate the effectiveness of the proposed method.

Nonuniform Changes in the Distribution of Visual Attention from Visual Complexity and Action: A Driving Simulation Study.

PubMed

Park, George D; Reed, Catherine L

2015-02-01

Researchers acknowledge the interplay between action and attention, but typically consider action as a response to successful attentional selection or the correlation of performance on separate action and attention tasks. We investigated how concurrent action with spatial monitoring affects the distribution of attention across the visual field. We embedded a functional field of view (FFOV) paradigm with concurrent central object recognition and peripheral target localization tasks in a simulated driving environment. Peripheral targets varied across 20-60 deg eccentricity at 11 radial spokes. Three conditions assessed the effects of visual complexity and concurrent action on the size and shape of the FFOV: (1) with no background, (2) with driving background, and (3) with driving background and vehicle steering. The addition of visual complexity slowed task performance and reduced the FFOV size but did not change the baseline shape. In contrast, the addition of steering produced not only shrinkage of the FFOV, but also changes in the FFOV shape. Nonuniform performance decrements occurred in proximal regions used for the central task and for steering, independent of interference from context elements. Multifocal attention models should consider the role of action and account for nonhomogeneities in the distribution of attention. © 2015 SAGE Publications.

Dietary Protein Intake and Distribution Patterns of Well-Trained Dutch Athletes.

PubMed

Gillen, Jenna B; Trommelen, Jorn; Wardenaar, Floris C; Brinkmans, Naomi Y J; Versteegen, Joline J; Jonvik, Kristin L; Kapp, Christoph; de Vries, Jeanne; van den Borne, Joost J G C; Gibala, Martin J; van Loon, Luc J C

2017-04-01

Dietary protein intake should be optimized in all athletes to ensure proper recovery and enhance the skeletal muscle adaptive response to exercise training. In addition to total protein intake, the use of specific proteincontaining food sources and the distribution of protein throughout the day are relevant for optimizing protein intake in athletes. In the present study, we examined the daily intake and distribution of various proteincontaining food sources in a large cohort of strength, endurance and team-sport athletes. Well-trained male (n=327) and female (n=226) athletes completed multiple web-based 24-hr dietary recalls over a 2-4 wk period. Total energy intake, the contribution of animal- and plant-based proteins to daily protein intake, and protein intake at six eating moments were determined. Daily protein intake averaged 108±33 and 90±24 g in men and women, respectively, which corresponded to relative intakes of 1.5±0.4 and 1.4±0.4 g/kg. Dietary protein intake was correlated with total energy intake in strength (r=0.71, p <.001), endurance (r=0.79, p <.001) and team-sport (r=0.77, p <.001) athletes. Animal and plant-based sources of protein intake was 57% and 43%, respectively. The distribution of protein intake was 19% (19±8 g) at breakfast, 24% (25±13 g) at lunch and 38% (38±15 g) at dinner. Protein intake was below the recommended 20 g for 58% of athletes at breakfast, 36% at lunch and 8% at dinner. In summary, this survey of athletes revealed they habitually consume > 1.2 g protein/kg/d, but the distribution throughout the day may be suboptimal to maximize the skeletal muscle adaptive response to training.

Forces Driving Chaperone Action

PubMed Central

Koldewey, Philipp; Stull, Frederick; Horowitz, Scott; Martin, Raoul; Bardwell, James C. A.

2016-01-01

SUMMARY It is still unclear what molecular forces drive chaperone-mediated protein folding. Here, we obtain a detailed mechanistic understanding of the forces that dictate the four key steps of chaperone-client interaction: initial binding, complex stabilization, folding, and release. Contrary to the common belief that chaperones recognize unfolding intermediates by their hydrophobic nature, we discover that the model chaperone Spy uses long-range electrostatic interactions to rapidly bind to its unfolded client protein Im7. Short-range hydrophobic interactions follow, which serve to stabilize the complex. Hydrophobic collapse of the client protein then drives its folding. By burying hydrophobic residues in its core, the client’s affinity to Spy decreases, which causes client release. By allowing the client to fold itself, Spy circumvents the need for client-specific folding instructions. This mechanism might help explain how chaperones can facilitate the folding of various unrelated proteins. PMID:27293188

Dietary Protein in Older Adults: Adequate Daily Intake but Potential for Improved Distribution.

PubMed

Cardon-Thomas, Danielle K; Riviere, Timothy; Tieges, Zoë; Greig, Carolyn A

2017-02-23

Daily distribution of dietary protein may be important in protecting against sarcopenia, specifically in terms of per meal amounts relative to a proposed threshold for maximal response. The aims of this study were to determine total and per meal protein intake in older adults, as well as identifying associations with physical activity and sedentary behavior. Three-day food diaries recorded protein intake in 38 participants. Protein distribution, coefficient of variation (CV), and per meal amounts were calculated. Accelerometry was used to collect physical activity data as well as volume and patterns of sedentary time. Average intake was 1.14 g·kg -1 ·day -1 . Distribution was uneven (CV = 0.67), and 79% of participants reported <0.4 g·kg -1 protein content in at least 2/3 daily meals. Protein intake was significantly correlated with step count ( r = 0.439, p = 0.007) and negatively correlated with sedentary time ( r = -0.456, p = 0.005) and Gini index G, which describes the pattern of accumulation of sedentary time ( r = -0.421, p = 0.011). Total daily protein intake was sufficient; however, distribution did not align with the current literature; increasing protein intake may help to facilitate optimization of distribution. Associations between protein and other risk factors for sarcopenia may also inform protective strategies.

Opportunities drive the global distribution of protected areas.

PubMed

Baldi, Germán; Texeira, Marcos; Martin, Osvaldo A; Grau, H Ricardo; Jobbágy, Esteban G

2017-01-01

Protected areas, regarded today as a cornerstone of nature conservation, result from an array of multiple motivations and opportunities. We explored at global and regional levels the current distribution of protected areas along biophysical, human, and biological gradients, and assessed to what extent protection has pursued (i) a balanced representation of biophysical environments, (ii) a set of preferred conditions (biological, spiritual, economic, or geopolitical), or (iii) existing opportunities for conservation regardless of any representation or preference criteria. We used histograms to describe the distribution of terrestrial protected areas along biophysical, human, and biological independent gradients and linear and non-linear regression and correlation analyses to describe the sign, shape, and strength of the relationships. We used a random forest analysis to rank the importance of different variables related to conservation preferences and opportunity drivers, and an evenness metric to quantify representativeness. We find that protection at a global level is primarily driven by the opportunities provided by isolation and a low population density (variable importance = 34.6 and 19.9, respectively). Preferences play a secondary role, with a bias towards tourism attractiveness and proximity to international borders (variable importance = 12.7 and 3.4, respectively). Opportunities shape protection strongly in "North America & Australia-NZ" and "Latin America & Caribbean," while the importance of the representativeness of biophysical environments is higher in "Sub-Saharan Africa" (1.3 times the average of other regions). Environmental representativeness and biodiversity protection are top priorities in land conservation agendas. However, our results suggest that they have been minor players driving current protection at both global and regional levels. Attempts to increase their relevance will necessarily have to recognize the predominant opportunistic nature

Opportunities drive the global distribution of protected areas

PubMed Central

Texeira, Marcos; Martin, Osvaldo A.; Grau, H. Ricardo; Jobbágy, Esteban G.

2017-01-01

Background Protected areas, regarded today as a cornerstone of nature conservation, result from an array of multiple motivations and opportunities. We explored at global and regional levels the current distribution of protected areas along biophysical, human, and biological gradients, and assessed to what extent protection has pursued (i) a balanced representation of biophysical environments, (ii) a set of preferred conditions (biological, spiritual, economic, or geopolitical), or (iii) existing opportunities for conservation regardless of any representation or preference criteria. Methods We used histograms to describe the distribution of terrestrial protected areas along biophysical, human, and biological independent gradients and linear and non-linear regression and correlation analyses to describe the sign, shape, and strength of the relationships. We used a random forest analysis to rank the importance of different variables related to conservation preferences and opportunity drivers, and an evenness metric to quantify representativeness. Results We find that protection at a global level is primarily driven by the opportunities provided by isolation and a low population density (variable importance = 34.6 and 19.9, respectively). Preferences play a secondary role, with a bias towards tourism attractiveness and proximity to international borders (variable importance = 12.7 and 3.4, respectively). Opportunities shape protection strongly in “North America & Australia–NZ” and “Latin America & Caribbean,” while the importance of the representativeness of biophysical environments is higher in “Sub-Saharan Africa” (1.3 times the average of other regions). Discussion Environmental representativeness and biodiversity protection are top priorities in land conservation agendas. However, our results suggest that they have been minor players driving current protection at both global and regional levels. Attempts to increase their relevance will necessarily

An Even Distribution of Protein Intake Daily Promotes Protein Adequacy but Does Not Influence Nutritional Status in Institutionalized Elderly.

PubMed

Tieland, Michael; Beelen, Janne; Laan, Anna C M; Poon, Shirley; de Groot, Lisette C P G M; Seeman, Ego; Wang, Xiaofang; Iuliano, Sandra

2018-01-01

Although it has been established that sufficient protein is required to maintain good nutritional status and support healthy aging, it is not clear if the pattern of protein consumption may also influence nutritional status, especially in institutionalized elderly who are at risk of malnutrition. Therefore, we aim to determine the association between protein intake distribution and nutritional status in institutionalized elderly people. Cross-sectional study among 481 institutionalized older adults. Dietary data from 481 ambulant elderly people (68.8% female, mean age 87.5 ± 6.3 years) residing in 52 aged-care facilities in Victoria, Australia, were assessed over 2 days using plate waste analysis. Nutritional status was determined using the Mini-Nutritional Assessment tool and serum (n = 208) analyzed for albumin, hemoglobin, and IGF-1. Protein intake distribution was classified as: spread (even distribution across 3 meals, n = 65), pulse (most protein consumed in one meal, n = 72) or intermediate (n = 344). Regression analysis was used to investigate associations. Mean protein intakes were higher in the spread (60.5 ± 2.0 g/d) than intermediate group (56.0 ± 0.8 g/d, P = .037), and tended to be higher than those in the pulse group (55.9 ± 1.9 g/d, P = .097). Residents with an even distribution of protein intake achieved a higher level of the recommended daily intake for protein (96.2 ± 30.0%) than the intermediate (86.3 ± 26.2%, P = .008) and pulse (87.4 ± 30.5%, P = .06) groups, and also achieved a greater level of their estimated energy requirements (intermediate; P = .039, pulse; P = .001). Nutritional status (Mini-Nutritional Assessment score) did not differ between groups (pulse; 20.5 ± 4.5, intermediate; 21.0 ± 2.5, spread; 20.5 ± 3.5), nor did any other indices of nutritional status. Meeting protein requirements is required before protein distribution may influence nutritional status in institutionalized

Distributed smoothed tree kernel for protein-protein interaction extraction from the biomedical literature

PubMed Central

Murugesan, Gurusamy; Abdulkadhar, Sabenabanu; Natarajan, Jeyakumar

2017-01-01

Automatic extraction of protein-protein interaction (PPI) pairs from biomedical literature is a widely examined task in biological information extraction. Currently, many kernel based approaches such as linear kernel, tree kernel, graph kernel and combination of multiple kernels has achieved promising results in PPI task. However, most of these kernel methods fail to capture the semantic relation information between two entities. In this paper, we present a special type of tree kernel for PPI extraction which exploits both syntactic (structural) and semantic vectors information known as Distributed Smoothed Tree kernel (DSTK). DSTK comprises of distributed trees with syntactic information along with distributional semantic vectors representing semantic information of the sentences or phrases. To generate robust machine learning model composition of feature based kernel and DSTK were combined using ensemble support vector machine (SVM). Five different corpora (AIMed, BioInfer, HPRD50, IEPA, and LLL) were used for evaluating the performance of our system. Experimental results show that our system achieves better f-score with five different corpora compared to other state-of-the-art systems. PMID:29099838

Distributed smoothed tree kernel for protein-protein interaction extraction from the biomedical literature.

PubMed

Murugesan, Gurusamy; Abdulkadhar, Sabenabanu; Natarajan, Jeyakumar

2017-01-01

Automatic extraction of protein-protein interaction (PPI) pairs from biomedical literature is a widely examined task in biological information extraction. Currently, many kernel based approaches such as linear kernel, tree kernel, graph kernel and combination of multiple kernels has achieved promising results in PPI task. However, most of these kernel methods fail to capture the semantic relation information between two entities. In this paper, we present a special type of tree kernel for PPI extraction which exploits both syntactic (structural) and semantic vectors information known as Distributed Smoothed Tree kernel (DSTK). DSTK comprises of distributed trees with syntactic information along with distributional semantic vectors representing semantic information of the sentences or phrases. To generate robust machine learning model composition of feature based kernel and DSTK were combined using ensemble support vector machine (SVM). Five different corpora (AIMed, BioInfer, HPRD50, IEPA, and LLL) were used for evaluating the performance of our system. Experimental results show that our system achieves better f-score with five different corpora compared to other state-of-the-art systems.

Universal distribution of mutational effects on protein stability, uncoupling of protein robustness from sequence evolution and distinct evolutionary modes of prokaryotic and eukaryotic proteins

NASA Astrophysics Data System (ADS)

Faure, Guilhem; Koonin, Eugene V.

2015-05-01

Robustness to destabilizing effects of mutations is thought of as a key factor of protein evolution. The connections between two measures of robustness, the relative core size and the computationally estimated effect of mutations on protein stability (ΔΔG), protein abundance and the selection pressure on protein-coding genes (dN/dS) were analyzed for the organisms with a large number of available protein structures including four eukaryotes, two bacteria and one archaeon. The distribution of the effects of mutations in the core on protein stability is universal and indistinguishable in eukaryotes and bacteria, centered at slightly destabilizing amino acid replacements, and with a heavy tail of more strongly destabilizing replacements. The distribution of mutational effects in the hyperthermophilic archaeon Thermococcus gammatolerans is significantly shifted toward strongly destabilizing replacements which is indicative of stronger constraints that are imposed on proteins in hyperthermophiles. The median effect of mutations is strongly, positively correlated with the relative core size, in evidence of the congruence between the two measures of protein robustness. However, both measures show only limited correlations to the expression level and selection pressure on protein-coding genes. Thus, the degree of robustness reflected in the universal distribution of mutational effects appears to be a fundamental, ancient feature of globular protein folds whereas the observed variations are largely neutral and uncoupled from short term protein evolution. A weak anticorrelation between protein core size and selection pressure is observed only for surface residues in prokaryotes but a stronger anticorrelation is observed for all residues in eukaryotic proteins. This substantial difference between proteins of prokaryotes and eukaryotes is likely to stem from the demonstrable higher compactness of prokaryotic proteins.

Effects of Acids, Bases, and Heteroatoms on Proximal Radial Distribution Functions for Proteins

PubMed Central

Nguyen, Bao Linh; Pettitt, B. Montgomery

2015-01-01

The proximal distribution of water around proteins is a convenient method of quantifying solvation. We consider the effect of charged and sulfur-containing amino acid side-chain atoms on the proximal radial distribution function (pRDF) of water molecules around proteins using side-chain analogs. The pRDF represents the relative probability of finding any solvent molecule at a distance from the closest or surface perpendicular protein atom. We consider the near-neighbor distribution. Previously, pRDFs were shown to be universal descriptors of the water molecules around C, N, and O atom types across hundreds of globular proteins. Using averaged pRDFs, a solvent density around any globular protein can be reconstructed with controllable relative error. Solvent reconstruction using the additional information from charged amino acid side-chain atom types from both small models and protein averages reveals the effects of surface charge distribution on solvent density and improves the reconstruction errors relative to simulation. Solvent density reconstructions from the small-molecule models are as effective and less computationally demanding than reconstructions from full macromolecular models in reproducing preferred hydration sites and solvent density fluctuations. PMID:26388706

Effects of Acids, Bases, and Heteroatoms on Proximal Radial Distribution Functions for Proteins.

PubMed

Nguyen, Bao Linh; Pettitt, B Montgomery

2015-04-14

The proximal distribution of water around proteins is a convenient method of quantifying solvation. We consider the effect of charged and sulfur-containing amino acid side-chain atoms on the proximal radial distribution function (pRDF) of water molecules around proteins using side-chain analogs. The pRDF represents the relative probability of finding any solvent molecule at a distance from the closest or surface perpendicular protein atom. We consider the near-neighbor distribution. Previously, pRDFs were shown to be universal descriptors of the water molecules around C, N, and O atom types across hundreds of globular proteins. Using averaged pRDFs, a solvent density around any globular protein can be reconstructed with controllable relative error. Solvent reconstruction using the additional information from charged amino acid side-chain atom types from both small models and protein averages reveals the effects of surface charge distribution on solvent density and improves the reconstruction errors relative to simulation. Solvent density reconstructions from the small-molecule models are as effective and less computationally demanding than reconstructions from full macromolecular models in reproducing preferred hydration sites and solvent density fluctuations.

Host trait combinations drive abundance and canopy distribution of atmospheric bromeliad assemblages.

PubMed

Chaves, Cleber Juliano Neves; Dyonisio, Júlio César; Rossatto, Davi Rodrigo

2016-01-01

Epiphytes are strongly dependent on the conditions created by their host's traits and a certain degree of specificity is expected between them, even if these species are largely abundant in a series of tree hosts of a given environment, as in the case of atmospheric bromeliads. Despite their considerable abundance in these environments, we hypothesize that stochasticity alone cannot explain the presence and abundance of atmospheric bromeliads on host trees, since host traits could have a greater influence on the establishment of these bromeliads. We used secondary and reforested seasonal forests and three distinct silvicultures to test whether species richness, phylogenetic diversity and functional diversity of trees can predict the differential presence, abundance and distribution of atmospheric bromeliads on hosts. We compared the observed parameters of their assemblage with null models and performed successive variance hierarchic partitions of abundance and distribution of the assemblage to detect the influence of multiple traits of the tree hosts. Our results do not indicate direct relationships between the abundance of atmospheric bromeliads and phylogenetic or functional diversity of trees, but instead indicate that bromeliads occurred on fewer tree species than expected by chance. We distinguished functional tree patterns that can improve or reduce the abundance of atmospheric bromeliads, and change their distribution on branches and trunk. While individual tree traits are related to increased abundance, species traits are related to the canopy distribution of atmospheric bromeliad assemblages. A balance among these tree functional patterns drives the atmospheric bromeliad assemblage of the forest patches. Published by Oxford University Press on behalf of the Annals of Botany Company.

Host trait combinations drive abundance and canopy distribution of atmospheric bromeliad assemblages

PubMed Central

Chaves, Cleber Juliano Neves; Dyonisio, Júlio César; Rossatto, Davi Rodrigo

2016-01-01

Epiphytes are strongly dependent on the conditions created by their host's traits and a certain degree of specificity is expected between them, even if these species are largely abundant in a series of tree hosts of a given environment, as in the case of atmospheric bromeliads. Despite their considerable abundance in these environments, we hypothesize that stochasticity alone cannot explain the presence and abundance of atmospheric bromeliads on host trees, since host traits could have a greater influence on the establishment of these bromeliads. We used secondary and reforested seasonal forests and three distinct silvicultures to test whether species richness, phylogenetic diversity and functional diversity of trees can predict the differential presence, abundance and distribution of atmospheric bromeliads on hosts. We compared the observed parameters of their assemblage with null models and performed successive variance hierarchic partitions of abundance and distribution of the assemblage to detect the influence of multiple traits of the tree hosts. Our results do not indicate direct relationships between the abundance of atmospheric bromeliads and phylogenetic or functional diversity of trees, but instead indicate that bromeliads occurred on fewer tree species than expected by chance. We distinguished functional tree patterns that can improve or reduce the abundance of atmospheric bromeliads, and change their distribution on branches and trunk. While individual tree traits are related to increased abundance, species traits are related to the canopy distribution of atmospheric bromeliad assemblages. A balance among these tree functional patterns drives the atmospheric bromeliad assemblage of the forest patches. PMID:26888951

Distribution, transition and thermodynamic stability of protein conformations in the denaturant-induced unfolding of proteins.

PubMed

Bian, Liujiao; Ji, Xu

2014-01-01

Extensive and intensive studies on the unfolding of proteins require appropriate theoretical model and parameter to clearly illustrate the feature and characteristic of the unfolding system. Over the past several decades, four approaches have been proposed to describe the interaction between proteins and denaturants, but some ambiguity and deviations usually occur in the explanation of the experimental data. In this work, a theoretical model was presented to show the dependency of the residual activity ratio of the proteins on the molar denaturant concentration. Through the characteristic unfolding parameters ki and Δmi in this model, the distribution, transition and thermodynamic stability of protein conformations during the unfolding process can be quantitatively described. This model was tested with the two-state unfolding of bovine heart cytochrome c and the three-state unfolding of hen egg white lysozyme induced by both guanidine hydrochloride and urea, the four-state unfolding of bovine carbonic anhydrase b induced by guanidine hydrochloride and the unfolding of some other proteins induced by denaturants. The results illustrated that this model could be used accurately to reveal the distribution and transition of protein conformations in the presence of different concentrations of denaturants and to evaluate the unfolding tendency and thermodynamic stability of different conformations. In most denaturant-induced unfolding of proteins, the unfolding became increasingly hard in next transition step and the proteins became more unstable as they attained next successive stable conformation. This work presents a useful method for people to study the unfolding of proteins and may be used to describe the unfolding and refolding of other biopolymers induced by denaturants, inducers, etc.

Wide distribution of cysteine-rich secretory proteins in snake venoms: isolation and cloning of novel snake venom cysteine-rich secretory proteins.

PubMed

Yamazaki, Yasuo; Hyodo, Fumiko; Morita, Takashi

2003-04-01

Cysteine-rich secretory proteins (CRISPs) are found in epididymis and granules of mammals, and they are thought to function in sperm maturation and in the immune system. Recently, we isolated and obtained clones for novel snake venom proteins that are classified as CRISP family proteins. To elucidate the distribution of snake venom CRISP family proteins, we evaluated a wide range of venoms for immuno-cross-reactivity. Then we isolated, characterized, and cloned genes for three novel CRISP family proteins (piscivorin, ophanin, and catrin) from the venom of eastern cottonmouth (Agkistrodon piscivorus piscivorus), king cobra (Ophiophagus hannah), and western diamondback rattlesnake (Crotalus atrox). Our results show the wide distribution of snake venom CRISP family proteins among Viperidae and Elapidae from different continents, indicating that CRISP family proteins compose a new group of snake venom proteins.

Evolution of patchily distributed proteins shared between eukaryotes and prokaryotes: Dictyostelium as a case study.

PubMed

Andersson, Jan O

2011-04-01

Protein families are often patchily distributed in the tree of life; they are present in distantly related organisms, but absent in more closely related lineages. This could either be the result of lateral gene transfer between ancestors of organisms that encode them, or losses in the lineages that lack them. Here a novel approach is developed to study the evolution of patchily distributed proteins shared between prokaryotes and eukaryotes. Proteins encoded in the genome of cellular slime mold Dictyostelium discoideum and a restricted number of other lineages, including at least one prokaryote, were identified. Analyses of the phylogenetic distribution of 49 such patchily distributed protein families showed conflicts with organismal phylogenies; 25 are shared with the distantly related amoeboflagellate Naegleria (Excavata), whereas only two are present in the more closely related Entamoeba. Most protein families show unexpected topologies in phylogenetic analyses; eukaryotes are polyphyletic in 85% of the trees. These observations suggest that gene transfers have been an important mechanism for the distribution of patchily distributed proteins across all domains of life. Further studies of this exchangeable gene fraction are needed for a better understanding of the origin and evolution of eukaryotic genes and the diversification process of eukaryotes. Copyright © 2011 S. Karger AG, Basel.

Protein distribution in lupin protein isolates from Lupinus angustifolius L. prepared by various isolation techniques.

PubMed

Muranyi, Isabel S; Volke, Daniela; Hoffmann, Ralf; Eisner, Peter; Herfellner, Thomas; Brunnbauer, Markus; Koehler, Peter; Schweiggert-Weisz, Ute

2016-09-15

Differences in the protein distribution of various protein isolates from Lupinus angustifolius L. Vitabor were identified as affected by the isolation procedure (alkaline and/or salt-induced extraction followed by isoelectric and/or dilutive precipitation). Protein isolates extracted in alkaline solution showed higher protein yields (26.4-31.7%) compared to salt-induced extraction (19.8-30.0%) or combined alkaline and salt-induced extraction (23.3-25.6%). Chemical variations among the protein isolates especially occurred within the albumins. Protein isolates precipitated isoelectrically showed the highest contents, whereas protein isolates precipitated by dilutive showed the lowest contents of conglutin δ. Furthermore, the alkaline subunits of conglutin α and conglutin γ decreased during alkaline extraction compared to salt-induced extraction. A decrease in protein-bound polar and basic amino acids was shown after protein isolation. In contrast, the amounts of nonpolar, aliphatic, aromatic, hydroxylated and sulfur-rich amino acids were higher in the lupin protein isolates compared to the lupin flakes. However, the functional side chains could not be related to the specific molecular arrangements of the protein isolates, as a similar amino acid composition was found among the protein isolates. Copyright © 2016 Elsevier Ltd. All rights reserved.

Protein charge distribution in proteomes and its impact on translation

PubMed Central

Requião, Rodrigo D.; Fernandes, Luiza; de Souza, Henrique José Araujo; Rossetto, Silvana; Domitrovic, Tatiana

2017-01-01

As proteins are synthesized, the nascent polypeptide must pass through a negatively charged exit tunnel. During this stage, positively charged stretches can interact with the ribosome walls and slow the translation. Therefore, charged polypeptides may be important factors that affect protein expression. To determine the frequency and distribution of positively and negatively charged stretches in different proteomes, the net charge was calculated for every 30 consecutive amino acid residues, which corresponds to the length of the ribosome exit tunnel. The following annotated and reviewed proteins in the UniProt database (Swiss-Prot) were analyzed: 551,705 proteins from different organisms and a total of 180 million protein segments. We observed that there were more negative than positive stretches and that super-charged positive sequences (i.e., net charges ≥ 14) were underrepresented in the proteomes. Overall, the proteins were more positively charged at their N-termini and C-termini, and this feature was present in most organisms and subcellular localizations. To investigate whether the N-terminal charges affect the elongation rates, previously published ribosomal profiling data obtained from S. cerevisiae, without translation-interfering drugs, were analyzed. We observed a nonlinear effect of the charge on the ribosome occupancy in which values ≥ +5 and ≤ -6 showed increased and reduced ribosome densities, respectively. These groups also showed different distributions across 80S monosomes and polysomes. Basic polypeptides are more common within short proteins that are translated by monosomes, whereas negative stretches are more abundant in polysome-translated proteins. These findings suggest that the nascent peptide charge impacts translation and can be one of the factors that regulate translation efficiency and protein expression. PMID:28531225

Integrated chassis control for a three-axle electric bus with distributed driving motors and active rear steering system

NASA Astrophysics Data System (ADS)

Liu, Wei; He, Hongwen; Sun, Fengchun; Lv, Jiangyi

2017-05-01

This paper describes an integrated chassis control framework for a novel three-axle electric bus with active rear steering (ARS) axle and four motors at the middle and rear wheels. The proposed integrated framework consists of four parts: (1) an active speed limiting controller is designed for anti-body slip control and rollover prevention; (2) an ARS controller is designed for coordinating the tyre wear between the driving wheels; (3) an inter-axle torque distribution controller is designed for optimal torque distribution between the axles, considering anti-wheel slip and battery power limitations and (4) a data acquisition and estimation module for collecting the measured and estimated vehicle states. To verify the performances, a simulation platform is established in Trucksim software combined with Simulink. Three test cases are particularly designed to show the performances. The proposed algorithm is compared with a simple even control algorithm. The test results show satisfactory lateral stability and rollover prevention performances under severe steering conditions. The desired tyre wear coordinating performance is also realised, and the wheel slip ratios are restricted within stable region during intensive driving and emergency braking with complicated road conditions.

Analyzing Protein Clusters on the Plasma Membrane: Application of Spatial Statistical Analysis Methods on Super-Resolution Microscopy Images.

PubMed

Paparelli, Laura; Corthout, Nikky; Pavie, Benjamin; Annaert, Wim; Munck, Sebastian

2016-01-01

The spatial distribution of proteins within the cell affects their capability to interact with other molecules and directly influences cellular processes and signaling. At the plasma membrane, multiple factors drive protein compartmentalization into specialized functional domains, leading to the formation of clusters in which intermolecule interactions are facilitated. Therefore, quantifying protein distributions is a necessity for understanding their regulation and function. The recent advent of super-resolution microscopy has opened up the possibility of imaging protein distributions at the nanometer scale. In parallel, new spatial analysis methods have been developed to quantify distribution patterns in super-resolution images. In this chapter, we provide an overview of super-resolution microscopy and summarize the factors influencing protein arrangements on the plasma membrane. Finally, we highlight methods for analyzing clusterization of plasma membrane proteins, including examples of their applications.

Exact protein distributions for stochastic models of gene expression using partitioning of Poisson processes.

PubMed

Pendar, Hodjat; Platini, Thierry; Kulkarni, Rahul V

2013-04-01

Stochasticity in gene expression gives rise to fluctuations in protein levels across a population of genetically identical cells. Such fluctuations can lead to phenotypic variation in clonal populations; hence, there is considerable interest in quantifying noise in gene expression using stochastic models. However, obtaining exact analytical results for protein distributions has been an intractable task for all but the simplest models. Here, we invoke the partitioning property of Poisson processes to develop a mapping that significantly simplifies the analysis of stochastic models of gene expression. The mapping leads to exact protein distributions using results for mRNA distributions in models with promoter-based regulation. Using this approach, we derive exact analytical results for steady-state and time-dependent distributions for the basic two-stage model of gene expression. Furthermore, we show how the mapping leads to exact protein distributions for extensions of the basic model that include the effects of posttranscriptional and posttranslational regulation. The approach developed in this work is widely applicable and can contribute to a quantitative understanding of stochasticity in gene expression and its regulation.

Exact protein distributions for stochastic models of gene expression using partitioning of Poisson processes

NASA Astrophysics Data System (ADS)

Pendar, Hodjat; Platini, Thierry; Kulkarni, Rahul V.

2013-04-01

Stochasticity in gene expression gives rise to fluctuations in protein levels across a population of genetically identical cells. Such fluctuations can lead to phenotypic variation in clonal populations; hence, there is considerable interest in quantifying noise in gene expression using stochastic models. However, obtaining exact analytical results for protein distributions has been an intractable task for all but the simplest models. Here, we invoke the partitioning property of Poisson processes to develop a mapping that significantly simplifies the analysis of stochastic models of gene expression. The mapping leads to exact protein distributions using results for mRNA distributions in models with promoter-based regulation. Using this approach, we derive exact analytical results for steady-state and time-dependent distributions for the basic two-stage model of gene expression. Furthermore, we show how the mapping leads to exact protein distributions for extensions of the basic model that include the effects of posttranscriptional and posttranslational regulation. The approach developed in this work is widely applicable and can contribute to a quantitative understanding of stochasticity in gene expression and its regulation.

Monte Carlo calculations of energy deposition distributions of electrons below 20 keV in protein.

PubMed

Tan, Zhenyu; Liu, Wei

2014-05-01

The distributions of energy depositions of electrons in semi-infinite bulk protein and the radial dose distributions of point-isotropic mono-energetic electron sources [i.e., the so-called dose point kernel (DPK)] in protein have been systematically calculated in the energy range below 20 keV, based on Monte Carlo methods. The ranges of electrons have been evaluated by extrapolating two calculated distributions, respectively, and the evaluated ranges of electrons are compared with the electron mean path length in protein which has been calculated by using electron inelastic cross sections described in this work in the continuous-slowing-down approximation. It has been found that for a given energy, the electron mean path length is smaller than the electron range evaluated from DPK, but it is large compared to the electron range obtained from the energy deposition distributions of electrons in semi-infinite bulk protein. The energy dependences of the extrapolated electron ranges based on the two investigated distributions are given, respectively, in a power-law form. In addition, the DPK in protein has also been compared with that in liquid water. An evident difference between the two DPKs is observed. The calculations presented in this work may be useful in studies of radiation effects on proteins.

Cellular distribution of calmodulin and calmodulin-binding proteins in Vicia faba L

NASA Technical Reports Server (NTRS)

Ling, V.; Assmann, S. M.

1992-01-01

The distribution of calmodulin (CaM) and CaM-binding proteins within Vicia faba was investigated. Both CaM and CaM-binding proteins were found to be differentially distributed among organs, tissues, and protoplast types. CaM levels, on a per protein basis, were found to be the highest in leaf epidermis, containing 3-fold higher levels of CaM than in total leaf. Similarly, guard cell and epidermal cell protoplasts were also found to have higher levels of CaM than mesophyll cell protoplasts. 125I-CaM blot overlay assays were performed to qualitatively examine CaM-binding proteins in these protoplast types as well as in whole tissues and organs. CaM-binding proteins with Mr 52,000, 78,000, and 115,000 were common in all metabolically active plant parts. Unique CaM-binding protein bands were detected in guard cell protoplasts (Mr 39,000, 88,000), stems (Mr 45,000, 60,000, 64,000), and roots (Mr 62,000), suggesting the presence of specialized CaM-dependent processes in these cells and organs.

Protein Translocation into the Intermembrane Space and Matrix of Mitochondria: Mechanisms and Driving Forces.

PubMed

Backes, Sandra; Herrmann, Johannes M

2017-01-01

Mitochondria contain two aqueous subcompartments, the matrix and the intermembrane space (IMS). The matrix is enclosed by both the inner and outer mitochondrial membranes, whilst the IMS is sandwiched between the two. Proteins of the matrix are synthesized in the cytosol as preproteins, which contain amino-terminal matrix targeting sequences that mediate their translocation through translocases embedded in the outer and inner membrane. For these proteins, the translocation reaction is driven by the import motor which is part of the inner membrane translocase. The import motor employs matrix Hsp70 molecules and ATP hydrolysis to ratchet proteins into the mitochondrial matrix. Most IMS proteins lack presequences and instead utilize the IMS receptor Mia40, which facilitates their translocation across the outer membrane in a reaction that is coupled to the formation of disulfide bonds within the protein. This process requires neither ATP nor the mitochondrial membrane potential. Mia40 fulfills two roles: First, it acts as a holdase, which is crucial in the import of IMS proteins and second, it functions as a foldase, introducing disulfide bonds into newly imported proteins, which induces and stabilizes their natively folded state. For several Mia40 substrates, oxidative folding is an essential prerequisite for their assembly into oligomeric complexes. Interestingly, recent studies have shown that the two functions of Mia40 can be experimentally separated from each other by the use of specific mutants, hence providing a powerful new way to dissect the different physiological roles of Mia40. In this review we summarize the current knowledge relating to the mitochondrial matrix-targeting and the IMS-targeting/Mia40 pathway. Moreover, we discuss the mechanistic properties by which the mitochondrial import motor on the one hand and Mia40 on the other, drive the translocation of their substrates into the organelle. We propose that the lateral diffusion of Mia40 in the inner

A tethering complex drives the terminal stage of SNARE-dependent membrane fusion

NASA Astrophysics Data System (ADS)

D'Agostino, Massimo; Risselada, Herre Jelger; Lürick, Anna; Ungermann, Christian; Mayer, Andreas

2017-11-01

Membrane fusion in eukaryotic cells mediates the biogenesis of organelles, vesicular traffic between them, and exo- and endocytosis of important signalling molecules, such as hormones and neurotransmitters. Distinct tasks in intracellular membrane fusion have been assigned to conserved protein systems. Tethering proteins mediate the initial recognition and attachment of membranes, whereas SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein complexes are considered as the core fusion engine. SNARE complexes provide mechanical energy to distort membranes and drive them through a hemifusion intermediate towards the formation of a fusion pore. This last step is highly energy-demanding. Here we combine the in vivo and in vitro fusion of yeast vacuoles with molecular simulations to show that tethering proteins are critical for overcoming the final energy barrier to fusion pore formation. SNAREs alone drive vacuoles only into the hemifused state. Tethering proteins greatly increase the volume of SNARE complexes and deform the site of hemifusion, which lowers the energy barrier for pore opening and provides the driving force. Thereby, tethering proteins assume a crucial mechanical role in the terminal stage of membrane fusion that is likely to be conserved at multiple steps of vesicular traffic. We therefore propose that SNAREs and tethering proteins should be considered as a single, non-dissociable device that drives fusion. The core fusion machinery may then be larger and more complex than previously thought.

Analysis of mammalian proteins involved in chromatin modification reveals new metaphase centromeric proteins and distinct chromosomal distribution patterns.

PubMed

Craig, Jeffrey M; Earle, Elizabeth; Canham, Paul; Wong, Lee H; Anderson, Melissa; Choo, K H Andy

2003-12-01

We have examined the metaphase chromosomal localization of 15 proteins that have previously been described as involved in mammalian chromatin modification and/or transcriptional modulation. Immunofluorescence data indicate that all the proteins localize to human and mouse centromeres, a neocentromere, and the active centromere of a dicentric chromosome, with six of these proteins (Sin3A, PCAF, MYST, MBD2, ORC2, P300/CBP) being demonstrated at mammalian centromeres for the first time. Most of these proteins fall into two distinct chromosomal distribution patterns: (a) kinetochore-associated proteins (Sin3A, PCAF, MYST and BAF180), which colocalize with metaphase kinetochores, but not any of the pericentric and other major heterochromatic regions; and (b) heterochromatin-associated proteins (MeCP2, MBD1, MBD2, ATRX, HP1alpha, HDAC1, HDAC2, DNMT1 and DNMT3b), which colocalize with centromeric/pericentric heterochromatin and all other major heterochromatic sites. A heterogeneous third group (c) consists of the origin recognition complex subunit ORC2 and the histone acetyltransferase P300/CBP, which associate generally with kinetochores in humans and centromeric/pericentric heterochromatin in mouse, with some minor differences in localization. These observations indicate an extensive sharing of protein components involved in chromatin modification at gene loci, centromeres and various chromosomal heterochromatic landmarks. The definition of distinct patterns of chromosomal distribution for these proteins provides a useful basis for the further investigation of the broad-ranging roles of these proteins.

Staphylococcus aureus FepA and FepB proteins drive heme iron utilization in Escherichia coli.

PubMed

Turlin, Evelyne; Débarbouillé, Michel; Augustyniak, Katarzyna; Gilles, Anne-Marie; Wandersman, Cécile

2013-01-01

EfeUOB-like tripartite systems are widespread in bacteria and in many cases they are encoded by genes organized into iron-regulated operons. They consist of: EfeU, a protein similar to the yeast iron permease Ftrp1; EfeO, an extracytoplasmic protein of unknown function and EfeB, also an extracytoplasmic protein with heme peroxidase activity, belonging to the DyP family. Many bacterial EfeUOB systems have been implicated in iron uptake, but a prefential iron source remains undetermined. Nevertheless, in the case of Escherichia coli, the EfeUOB system has been shown to recognize heme and to allow extracytoplasmic heme iron extraction via a deferrochelation reaction. Given the high level of sequence conservations between EfeUOB orthologs, we hypothesized that heme might be the physiological iron substrate for the other orthologous systems. To test this hypothesis, we undertook characterization of the Staphylococcus aureus FepABC system. Results presented here indicate: i) that the S. aureus FepB protein binds both heme and PPIX with high affinity, like EfeB, the E. coli ortholog; ii) that it has low peroxidase activity, comparable to that of EfeB; iii) that both FepA and FepB drive heme iron utilization, and both are required for this activity and iv) that the E. coli FepA ortholog (EfeO) cannot replace FepA in FepB-driven iron release from heme indicating protein specificity in these activities. Our results show that the function in heme iron extraction is conserved in the two orthologous systems.

Effect of mahlep on molecular weight distribution of cookie flour gluten proteins

USDA-ARS?s Scientific Manuscript database

Size Exclusion-High performance Chromatography (SE-HPLC) has been extensively used in molecular weight distribution analysis of wheat proteins. In this study the protein analysis was conducted on different cookie dough blends with different percentages of some ingredients. The mean chromatography ...

iDriving (Intelligent Driving)

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

Malikopoulos, Andreas

2012-09-17

iDriving identifies the driving style factors that have a major impact on fuel economy. An optimization framework is used with the aim of optimizing a driving style with respect to these driving factors. A set of polynomial metamodels is constructed to reflect the responses produced in fuel economy by changing the driving factors. The optimization framework is used to develop a real-time feedback system, including visual instructions, to enable drivers to alter their driving styles in responses to actual driving conditions to improve fuel efficiency.

Evolution of an intricate J-protein network driving protein disaggregation in eukaryotes.

PubMed

Nillegoda, Nadinath B; Stank, Antonia; Malinverni, Duccio; Alberts, Niels; Szlachcic, Anna; Barducci, Alessandro; De Los Rios, Paolo; Wade, Rebecca C; Bukau, Bernd

2017-05-15

Hsp70 participates in a broad spectrum of protein folding processes extending from nascent chain folding to protein disaggregation. This versatility in function is achieved through a diverse family of J-protein cochaperones that select substrates for Hsp70. Substrate selection is further tuned by transient complexation between different classes of J-proteins, which expands the range of protein aggregates targeted by metazoan Hsp70 for disaggregation. We assessed the prevalence and evolutionary conservation of J-protein complexation and cooperation in disaggregation. We find the emergence of a eukaryote-specific signature for interclass complexation of canonical J-proteins. Consistently, complexes exist in yeast and human cells, but not in bacteria, and correlate with cooperative action in disaggregation in vitro. Signature alterations exclude some J-proteins from networking, which ensures correct J-protein pairing, functional network integrity and J-protein specialization. This fundamental change in J-protein biology during the prokaryote-to-eukaryote transition allows for increased fine-tuning and broadening of Hsp70 function in eukaryotes.

The De Novo Design of Protein-Protein Interfaces

DTIC Science & Technology

it was our intention to add to this body by engineering de novo (from scratch) protein/protein complexes. Using this inverse approach we have furthered...key physical features needed to drive specific protein/protein interactions. It is considered inverse because, instead of studying natural complexes

Systematic analysis of mutation distribution in three dimensional protein structures identifies cancer driver genes.

PubMed

Fujimoto, Akihiro; Okada, Yukinori; Boroevich, Keith A; Tsunoda, Tatsuhiko; Taniguchi, Hiroaki; Nakagawa, Hidewaki

2016-05-26

Protein tertiary structure determines molecular function, interaction, and stability of the protein, therefore distribution of mutation in the tertiary structure can facilitate the identification of new driver genes in cancer. To analyze mutation distribution in protein tertiary structures, we applied a novel three dimensional permutation test to the mutation positions. We analyzed somatic mutation datasets of 21 types of cancers obtained from exome sequencing conducted by the TCGA project. Of the 3,622 genes that had ≥3 mutations in the regions with tertiary structure data, 106 genes showed significant skew in mutation distribution. Known tumor suppressors and oncogenes were significantly enriched in these identified cancer gene sets. Physical distances between mutations in known oncogenes were significantly smaller than those of tumor suppressors. Twenty-three genes were detected in multiple cancers. Candidate genes with significant skew of the 3D mutation distribution included kinases (MAPK1, EPHA5, ERBB3, and ERBB4), an apoptosis related gene (APP), an RNA splicing factor (SF1), a miRNA processing factor (DICER1), an E3 ubiquitin ligase (CUL1) and transcription factors (KLF5 and EEF1B2). Our study suggests that systematic analysis of mutation distribution in the tertiary protein structure can help identify cancer driver genes.

Systematic analysis of mutation distribution in three dimensional protein structures identifies cancer driver genes

PubMed Central

Fujimoto, Akihiro; Okada, Yukinori; Boroevich, Keith A.; Tsunoda, Tatsuhiko; Taniguchi, Hiroaki; Nakagawa, Hidewaki

2016-01-01

Protein tertiary structure determines molecular function, interaction, and stability of the protein, therefore distribution of mutation in the tertiary structure can facilitate the identification of new driver genes in cancer. To analyze mutation distribution in protein tertiary structures, we applied a novel three dimensional permutation test to the mutation positions. We analyzed somatic mutation datasets of 21 types of cancers obtained from exome sequencing conducted by the TCGA project. Of the 3,622 genes that had ≥3 mutations in the regions with tertiary structure data, 106 genes showed significant skew in mutation distribution. Known tumor suppressors and oncogenes were significantly enriched in these identified cancer gene sets. Physical distances between mutations in known oncogenes were significantly smaller than those of tumor suppressors. Twenty-three genes were detected in multiple cancers. Candidate genes with significant skew of the 3D mutation distribution included kinases (MAPK1, EPHA5, ERBB3, and ERBB4), an apoptosis related gene (APP), an RNA splicing factor (SF1), a miRNA processing factor (DICER1), an E3 ubiquitin ligase (CUL1) and transcription factors (KLF5 and EEF1B2). Our study suggests that systematic analysis of mutation distribution in the tertiary protein structure can help identify cancer driver genes. PMID:27225414

Analysis of cache for streaming tape drive

NASA Technical Reports Server (NTRS)

Chinnaswamy, V.

1993-01-01

A tape subsystem consists of a controller and a tape drive. Tapes are used for backup, data interchange, and software distribution. The backup operation is addressed. During a backup operation, data is read from disk, processed in CPU, and then sent to tape. The processing speeds of a disk subsystem, CPU, and a tape subsystem are likely to be different. A powerful CPU can read data from a fast disk, process it, and supply the data to the tape subsystem at a faster rate than the tape subsystem can handle. On the other hand, a slow disk drive and a slow CPU may not be able to supply data fast enough to keep a tape drive busy all the time. The backup process may supply data to tape drive in bursts. Each burst may be followed by an idle period. Depending on the nature of the file distribution in the disk, the input stream to the tape subsystem may vary significantly during backup. To compensate for these differences and optimize the utilization of a tape subsystem, a cache or buffer is introduced in the tape controller. Most of the tape drives today are streaming tape drives. A streaming tape drive goes into reposition when there is no data from the controller. Once the drive goes into reposition, the controller can receive data, but it cannot supply data to the tape drive until the drive completes its reposition. A controller can also receive data from the host and send data to the tape drive at the same time. The relationship of cache size, host transfer rate, drive transfer rate, reposition, and ramp up times for optimal performance of the tape subsystem are investigated. Formulas developed will also show the advantages of cache watermarks to increase the streaming time of the tape drive, maximum loss due to insufficient cache, tradeoffs between cache and reposition times and the effectiveness of cache on a streaming tape drive due to idle times or interruptions due in host transfers. Several mathematical formulas are developed to predict the performance of the tape

Distribution of PASTA domains in penicillin-binding proteins and serine/threonine kinases of Actinobacteria.

PubMed

Ogawara, Hiroshi

2016-09-01

PASTA domains (penicillin-binding protein and serine/threonine kinase-associated domains) have been identified in penicillin-binding proteins and serine/threonine kinases of Gram-positive Firmicutes and Actinobacteria. They are believed to bind β-lactam antibiotics, and be involved in peptidoglycan metabolism, although their biological function is not definitively clarified. Actinobacteria, especially Streptomyces species, are distinct in that they undergo complex cellular differentiation and produce various antibiotics including β-lactams. This review focuses on the distribution of PASTA domains in penicillin-binding proteins and serine/threonine kinases in Actinobacteria. In Actinobacteria, PASTA domains are detectable exclusively in class A but not in class B penicillin-binding proteins, in sharp contrast to the cases in other bacteria. In penicillin-binding proteins, PASTA domains distribute independently from taxonomy with some distribution bias. Particularly interesting thing is that no Streptomyces species have penicillin-binding protein with PASTA domains. Protein kinases in Actinobacteria possess 0 to 5 PASTA domains in their molecules. Protein kinases in Streptomyces can be classified into three groups: no PASTA domain, 1 PASTA domain and 4 PASTA domain-containing groups. The 4 PASTA domain-containing groups can be further divided into two subgroups. The serine/threonine kinases in different groups may perform different functions. The pocket region in one of these subgroup is more dense and extended, thus it may be involved in binding of ligands like β-lactams more efficiently.

Assessing protein conformational sampling methods based on bivariate lag-distributions of backbone angles

PubMed Central

Maadooliat, Mehdi; Huang, Jianhua Z.

2013-01-01

Despite considerable progress in the past decades, protein structure prediction remains one of the major unsolved problems in computational biology. Angular-sampling-based methods have been extensively studied recently due to their ability to capture the continuous conformational space of protein structures. The literature has focused on using a variety of parametric models of the sequential dependencies between angle pairs along the protein chains. In this article, we present a thorough review of angular-sampling-based methods by assessing three main questions: What is the best distribution type to model the protein angles? What is a reasonable number of components in a mixture model that should be considered to accurately parameterize the joint distribution of the angles? and What is the order of the local sequence–structure dependency that should be considered by a prediction method? We assess the model fits for different methods using bivariate lag-distributions of the dihedral/planar angles. Moreover, the main information across the lags can be extracted using a technique called Lag singular value decomposition (LagSVD), which considers the joint distribution of the dihedral/planar angles over different lags using a nonparametric approach and monitors the behavior of the lag-distribution of the angles using singular value decomposition. As a result, we developed graphical tools and numerical measurements to compare and evaluate the performance of different model fits. Furthermore, we developed a web-tool (http://www.stat.tamu.edu/∼madoliat/LagSVD) that can be used to produce informative animations. PMID:22926831

Conjugates of ubiquitin cross-reactive protein distribute in a cytoskeletal pattern.

PubMed Central

Loeb, K R; Haas, A L

1994-01-01

Ubiquitin cross-reactive protein (UCRP), a 15-kDa interferon-induced protein, is a sequence homolog of ubiquitin that is covalently ligated to intracellular proteins in a parallel enzymatic reaction and is found at low levels within cultured cell lines and human tissues not exposed to interferon. Ubiquitin and UCRP ligation reactions apparently target distinct subsets of intracellular proteins, as judged from differences in the distributions of the respective adducts revealed on immunoblots. In this study, successive passages of the human lung carcinoma line A549 in the presence of neutralizing antibodies against alpha and beta interferons had no effect on the levels of either free or conjugated UCRP, indicating that these UCRP pools are constitutively present within uninduced cells and are thus not a consequence of autoinduction by low levels of secreted alpha/beta interferon. In an effort to identify potential targets for UCRP conjugation, the immunocytochemical distribution of UCRP was examined by using affinity-purified polyclonal antibodies against recombinant polypeptide. UCRP distributes in a punctate cytoskeletal pattern that is resistant to extraction by nonionic detergents (e.g., Triton X-100) in both uninduced and interferon-treated A549 cells. The cytoskeletal pattern colocalizes with the intermediate filament network of epithelial and mesothelial cell lines. Immunoblots of parallel Triton X-100-insoluble cell extracts suggest that the cytoskeletal association largely results from the noncovalent association of UCRP conjugates with the intermediate filaments rather than direct ligation of the polypeptide to structural components of the filaments. A significant increase in the sequestration of UCRP adducts on intermediate filaments accompanies interferon induction. These results suggest that UCRP may serve as a trans-acting binding factor directing the association of ligated target proteins to intermediate filaments. Images PMID:7526157

The Respiratory Syncytial Virus Phosphoprotein, Matrix Protein, and Fusion Protein Carboxy-Terminal Domain Drive Efficient Filamentous Virus-Like Particle Formation

PubMed Central

Meshram, Chetan D.; Baviskar, Pradyumna S.; Ognibene, Cherie M.

2016-01-01

ABSTRACT Virus-like particles (VLPs) are attractive as a vaccine concept. For human respiratory syncytial virus (hRSV), VLP assembly is poorly understood and appears inefficient. Hence, hRSV antigens are often incorporated into foreign VLP systems to generate anti-RSV vaccine candidates. To better understand the assembly, and ultimately to enable efficient production, of authentic hRSV VLPs, we examined the associated requirements and mechanisms. In a previous analysis in HEp-2 cells, the nucleoprotein (N), phosphoprotein (P), matrix protein (M), and fusion protein (F) were required for formation of filamentous VLPs, which, similar to those of wild-type virus, were associated with the cell surface. Using fluorescence and electron microscopy combined with immunogold labeling, we examined the surfaces of transfected HEp-2 cells and further dissected the process of filamentous VLP formation. Our results show that N is not required. Coexpression of P plus M plus F, but not P plus M, M plus F, or P plus F, induced both viral protein coalescence and formation of filamentous VLPs that resembled wild-type virions. Despite suboptimal coalescence in the absence of P, the M and F proteins, when coexpressed, formed cell surface-associated filaments with abnormal morphology, appearing longer and thinner than wild-type virions. For F, only the carboxy terminus (Fstem) was required, and addition of foreign protein sequences to Fstem allowed incorporation into VLPs. Together, the data show that P, M, and the F carboxy terminus are sufficient for robust viral protein coalescence and filamentous VLP formation and suggest that M-F interaction drives viral filament formation, with P acting as a type of cofactor facilitating the process and exerting control over particle morphology. IMPORTANCE hRSV is responsible for >100,000 deaths in children worldwide, and a vaccine is not available. Among the potential anti-hRSV approaches are virus-like particle (VLP) vaccines, which, based on

Membrane Bending by Protein Crowding

NASA Astrophysics Data System (ADS)

Stachowiak, Jeanne

2014-03-01

From endosomes and synaptic vesicles to the cristae of the mitochondria and the annulus of the nuclear pore, highly curved membranes are fundamental to the structure and physiology of living cells. The established view is that specific families of proteins are able to bend membranes by binding to them. For example, inherently curved proteins are thought to impose their structure on the membrane surface, while membrane-binding proteins with hydrophobic motifs are thought to insert into the membrane like wedges, driving curvature. However, computational models have recently revealed that these mechanisms would require specialized membrane-bending proteins to occupy nearly 100% of a curved membrane surface, an improbable physiological situation given the immense density and diversity of membrane-bound proteins, and the low expression levels of these specialized proteins within curved regions of the membrane. How then does curvature arise within the complex and crowded environment of cellular membranes? Our recent work using proteins involved in clathrin-mediated endocytosis, as well as engineered protein-lipid interactions, has suggested a new hypothesis - that lateral pressure generated by collisions between membrane-bound proteins can drive membrane bending. Specifically, by correlating membrane bending with quantitative optical measurements of protein density on synthetic membrane surfaces and simple physical models of collisions among membrane-bound proteins, we have demonstrated that protein-protein steric interactions can drive membrane curvature. These findings suggest that a simple imbalance in the concentration of membrane-bound proteins across a membrane surface can drive a membrane to bend, providing an efficient mechanism by which essentially any protein can contribute to shaping membranes.

Protein-Protein Interactions in Clathrin Vesicular Assembly: Radial Distribution of Evolutionary Constraints in Interfaces

PubMed Central

Gadkari, Rupali A.; Srinivasan, Narayanaswamy

2012-01-01

In eukaryotic organisms clathrin-coated vesicles are instrumental in the processes of endocytosis as well as intracellular protein trafficking. Hence, it is important to understand how these vesicles have evolved across eukaryotes, to carry cargo molecules of varied shapes and sizes. The intricate nature and functional diversity of the vesicles are maintained by numerous interacting protein partners of the vesicle system. However, to delineate functionally important residues participating in protein-protein interactions of the assembly is a daunting task as there are no high-resolution structures of the intact assembly available. The two cryoEM structures closely representing intact assembly were determined at very low resolution and provide positions of Cα atoms alone. In the present study, using the method developed by us earlier, we predict the protein-protein interface residues in clathrin assembly, taking guidance from the available low-resolution structures. The conservation status of these interfaces when investigated across eukaryotes, revealed a radial distribution of evolutionary constraints, i.e., if the members of the clathrin vesicular assembly can be imagined to be arranged in spherical manner, the cargo being at the center and clathrins being at the periphery, the detailed phylogenetic analysis of these members of the assembly indicated high-residue variation in the members of the assembly closer to the cargo while high conservation was noted in clathrins and in other proteins at the periphery of the vesicle. This points to the strategy adopted by the nature to package diverse proteins but transport them through a highly conserved mechanism. PMID:22384024

Distribution of protein poly(ADP-ribosyl)ation systems across all domains of life

PubMed Central

Perina, Dragutin; Mikoč, Andreja; Ahel, Josip; Ćetković, Helena; Žaja, Roko; Ahel, Ivan

2014-01-01

Poly(ADP-ribosyl)ation is a post-translational modification of proteins involved in regulation of many cellular pathways. Poly(ADP-ribose) (PAR) consists of chains of repeating ADP-ribose nucleotide units and is synthesized by the family of enzymes called poly(ADP-ribose) polymerases (PARPs). This modification can be removed by the hydrolytic action of poly(ADP-ribose) glycohydrolase (PARG) and ADP-ribosylhydrolase 3 (ARH3). Hydrolytic activity of macrodomain proteins (MacroD1, MacroD2 and TARG1) is responsible for the removal of terminal ADP-ribose unit and for complete reversion of protein ADP-ribosylation. Poly(ADP-ribosyl)ation is widely utilized in eukaryotes and PARPs are present in representatives from all six major eukaryotic supergroups, with only a small number of eukaryotic species that do not possess PARP genes. The last common ancestor of all eukaryotes possessed at least five types of PARP proteins that include both mono and poly(ADP-ribosyl) transferases. Distribution of PARGs strictly follows the distribution of PARP proteins in eukaryotic species. At least one of the macrodomain proteins that hydrolyse terminal ADP-ribose is also always present. Therefore, we can presume that the last common ancestor of all eukaryotes possessed a fully functional and reversible PAR metabolism and that PAR signalling provided the conditions essential for survival of the ancestral eukaryote in its ancient environment. PARP proteins are far less prevalent in bacteria and were probably gained through horizontal gene transfer. Only eleven bacterial species possess all proteins essential for a functional PAR metabolism, although it is not known whether PAR metabolism is truly functional in bacteria. Several dsDNA viruses also possess PARP homologues, while no PARP proteins have been identified in any archaeal genome. Our analysis of the distribution of enzymes involved in PAR metabolism provides insight into the evolution of these important signalling systems, as well as

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

PubMed

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

2016-07-05

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

Distributions of experimental protein structures on coarse-grained free energy landscapes

PubMed Central

Liu, Jie; Jernigan, Robert L.

2015-01-01

Predicting conformational changes of proteins is needed in order to fully comprehend functional mechanisms. With the large number of available structures in sets of related proteins, it is now possible to directly visualize the clusters of conformations and their conformational transitions through the use of principal component analysis. The most striking observation about the distributions of the structures along the principal components is their highly non-uniform distributions. In this work, we use principal component analysis of experimental structures of 50 diverse proteins to extract the most important directions of their motions, sample structures along these directions, and estimate their free energy landscapes by combining knowledge-based potentials and entropy computed from elastic network models. When these resulting motions are visualized upon their coarse-grained free energy landscapes, the basis for conformational pathways becomes readily apparent. Using three well-studied proteins, T4 lysozyme, serum albumin, and sarco-endoplasmic reticular Ca2+ adenosine triphosphatase (SERCA), as examples, we show that such free energy landscapes of conformational changes provide meaningful insights into the functional dynamics and suggest transition pathways between different conformational states. As a further example, we also show that Monte Carlo simulations on the coarse-grained landscape of HIV-1 protease can directly yield pathways for force-driven conformational changes. PMID:26723638

Stone former urine proteome demonstrates a cationic shift in protein distribution compared to normal.

PubMed

Kolbach-Mandel, Ann M; Mandel, Neil S; Hoffmann, Brian R; Kleinman, Jack G; Wesson, Jeffrey A

2017-08-01

Many urine proteins are found in calcium oxalate stones, yet decades of research have failed to define the role of urine proteins in stone formation. This urine proteomic study compares the relative amounts of abundant urine proteins between idiopathic calcium oxalate stone forming and non-stone forming (normal) cohorts to identify differences that might correlate with disease. Random mid-morning urine samples were collected following informed consent from 25 stone formers and 14 normal individuals. Proteins were isolated from urine using ultrafiltration. Urine proteomes for each sample were characterized using label-free spectral counting mass spectrometry, so that urine protein relative abundances could be compared between the two populations. A total of 407 unique proteins were identified with the 38 predominant proteins accounting for >82% of all sample spectral counts. The most highly abundant proteins were equivalent in stone formers and normals, though significant differences were observed in a few moderate abundance proteins (immunoglobulins, transferrin, and epidermal growth factor), accounting for 13 and 10% of the spectral counts, respectively. These proteins contributed to a cationic shift in protein distribution in stone formers compared to normals (22% vs. 18%, p = 0.04). Our data showing only small differences in moderate abundance proteins suggest that no single protein controls stone formation. Observed increases in immunoglobulins and transferrin suggest increased inflammatory activity in stone formers, but cannot distinguish cause from effect in stone formation. The observed cationic shift in protein distribution would diminish protein charge stabilization, which could lead to protein aggregation and increased risk for crystal aggregation.

Composition and molecular weight distribution of carob germ protein fractions.

PubMed

Smith, Brennan M; Bean, Scott R; Schober, Tilman J; Tilley, Michael; Herald, Thomas J; Aramouni, Fadi

2010-07-14

Biochemical properties of carob germ proteins were analyzed using a combination of selective extraction, reversed-phase high-performance liquid chromatography (RP-HPLC), size exclusion chromatography (SEC) coupled with multiangle laser light scattering (SEC-MALS), and electrophoretic analysis. Using a modified Osborne extraction procedure, carob germ flour proteins were found to contain approximately 32% albumin and globulin and approximately 68% glutelin with no prolamins detected. The albumin and globulin fraction was found to contain low amounts of disulfide-bonded polymers with relatively low M(w) ranging up to 5 x 10(6) Da. The glutelin fraction, however, was found to contain large amounts of high molecular weight disulfide-bonded polymers with M(w) up to 8 x 10(7) Da. When extracted under nonreducing conditions and divided into soluble and insoluble proteins as typically done for wheat gluten, carob germ proteins were found to be almost entirely ( approximately 95%) in the soluble fraction with only ( approximately 5%) in the insoluble fraction. As in wheat, SEC-MALS analysis showed that the insoluble proteins had a greater M(w) than the soluble proteins and ranged up to 8 x 10(7) Da. The lower M(w) distribution of the polymeric proteins of carob germ flour may account for differences in functionality between wheat and carob germ flour.

Temperature and nitrogen supply interact to determine protein distribution gradients in the wheat grain endosperm.

PubMed

Savill, George P; Michalski, Adam; Powers, Stephen J; Wan, Yongfang; Tosi, Paola; Buchner, Peter; Hawkesford, Malcolm J

2018-05-25

Gradients exist in the distribution of storage proteins in the wheat (Triticum aestivum) endosperm and determine the milling properties and protein recovery rate of the grain. A novel image analysis technique was developed to quantify both the gradients in protein concentration, and the size distribution of protein bodies within the endosperm of wheat plants grown under two different (20 or 28 °C) post-anthesis temperatures, and supplied with a nutrient solution with either high or low nitrogen content. Under all treatment combinations, protein concentration was greater in the endosperm cells closest to the aleurone layer and decreased towards the centre of the two lobes of the grain, i.e. a negative gradient. This was accompanied by a decrease in size of protein bodies from the outer to the inner endosperm layers in all but one of the treatments. Elevated post-anthesis temperature had the effect of increasing the magnitude of the negative gradients in both protein concentration and protein body size, whilst limiting nitrogen supply decreased the gradients.

Audio distribution and Monitoring Circuit

NASA Technical Reports Server (NTRS)

Kirkland, J. M.

1983-01-01

Versatile circuit accepts and distributes TV audio signals. Three-meter audio distribution and monitoring circuit provides flexibility in monitoring, mixing, and distributing audio inputs and outputs at various signal and impedance levels. Program material is simultaneously monitored on three channels, or single-channel version built to monitor transmitted or received signal levels, drive speakers, interface to building communications, and drive long-line circuits.

Interference from Proteins and Surfactants on Particle Size Distributions Measured by Nanoparticle Tracking Analysis (NTA).

PubMed

Bai, Kelvin; Barnett, Gregory V; Kar, Sambit R; Das, Tapan K

2017-04-01

Characterization of submicron protein particles continues to be challenging despite active developments in the field. NTA is a submicron particle enumeration technique, which optically tracks the light scattering signal from suspended particles undergoing Brownian motion. The submicron particle size range NTA can monitor in common protein formulations is not well established. We conducted a comprehensive investigation with several protein formulations along with corresponding placebos using NTA to determine submicron particle size distributions and shed light on potential non-particle origin of size distribution in the range of approximately 50-300 nm. NTA and DLS are performed on polystyrene size standards as well as protein and placebo formulations. Protein formulations filtered through a 20 nm filter, with and without polysorbate-80, show NTA particle counts. As such, particle counts above 20 nm are not expected in these solutions. Several other systems including positive and negative controls were studied using NTA and DLS. These apparent particles measured by NTA are not observed in DLS measurements and may not correspond to real particles. The intent of this article is to raise awareness about the need to interpret particle counts and size distribution from NTA with caution.

Spatial gene drives and pushed genetic waves.

PubMed

Tanaka, Hidenori; Stone, Howard A; Nelson, David R

2017-08-08

Gene drives have the potential to rapidly replace a harmful wild-type allele with a gene drive allele engineered to have desired functionalities. However, an accidental or premature release of a gene drive construct to the natural environment could damage an ecosystem irreversibly. Thus, it is important to understand the spatiotemporal consequences of the super-Mendelian population genetics before potential applications. Here, we use a reaction-diffusion model for sexually reproducing diploid organisms to study how a locally introduced gene drive allele spreads to replace the wild-type allele, although it possesses a selective disadvantage s > 0. Using methods developed by Barton and collaborators, we show that socially responsible gene drives require 0.5 < s < 0.697, a rather narrow range. In this "pushed wave" regime, the spatial spreading of gene drives will be initiated only when the initial frequency distribution is above a threshold profile called "critical propagule," which acts as a safeguard against accidental release. We also study how the spatial spread of the pushed wave can be stopped by making gene drives uniquely vulnerable ("sensitizing drive") in a way that is harmless for a wild-type allele. Finally, we show that appropriately sensitized drives in two dimensions can be stopped, even by imperfect barriers perforated by a series of gaps.

Distribution of gluten proteins in bread wheat (Triticum aestivum) grain.

PubMed

Tosi, Paola; Gritsch, Cristina Sanchis; He, Jibin; Shewry, Peter R

2011-07-01

Gluten proteins are the major storage protein fraction in the mature wheat grain. They are restricted to the starchy endosperm, which forms white flour on milling, and interact during grain development to form large polymers which form a continuous proteinaceous network when flour is mixed with water to give dough. This network confers viscosity and elasticity to the dough, enabling the production of leavened products. The starchy endosperm is not a homogeneous tissue and quantitative and qualitative gradients exist for the major components: protein, starch and cell wall polysaccharides. Gradients in protein content and composition are the most evident and are of particular interest because of the major role played by the gluten proteins in determining grain processing quality. Protein gradients in the starchy endosperm were investigated using antibodies for specific gluten protein types for immunolocalization in developing grains and for western blot analysis of protein extracts from flour fractions obtained by sequential abrasion (pearling) to prepare tissue layers. Differential patterns of distribution were found for the high-molecular-weight subunits of glutenin (HMW-GS) and γ-gliadins when compared with the low-molecular-weight subunits of glutenin (LMW-GS), ω- and α-gliadins. The first two types of gluten protein are more abundant in the inner endosperm layers and the latter more abundant in the subaleurone. Immunolocalization also showed that segregation of gluten proteins occurs both between and within protein bodies during protein deposition and may still be retained in the mature grain. Quantitative and qualitative gradients in gluten protein composition are established during grain development. These gradients may be due to the origin of subaleurone cells, which unlike other starchy endosperm cells derive from the re-differentiation of aleurone cells, but could also result from the action of specific regulatory signals produced by the maternal tissue

Genome-wide survey of DNA-binding proteins in Arabidopsis thaliana: analysis of distribution and functions.

PubMed

Malhotra, Sony; Sowdhamini, Ramanathan

2013-08-01

The interaction of proteins with their respective DNA targets is known to control many high-fidelity cellular processes. Performing a comprehensive survey of the sequenced genomes for DNA-binding proteins (DBPs) will help in understanding their distribution and the associated functions in a particular genome. Availability of fully sequenced genome of Arabidopsis thaliana enables the review of distribution of DBPs in this model plant genome. We used profiles of both structure and sequence-based DNA-binding families, derived from PDB and PFam databases, to perform the survey. This resulted in 4471 proteins, identified as DNA-binding in Arabidopsis genome, which are distributed across 300 different PFam families. Apart from several plant-specific DNA-binding families, certain RING fingers and leucine zippers also had high representation. Our search protocol helped to assign DNA-binding property to several proteins that were previously marked as unknown, putative or hypothetical in function. The distribution of Arabidopsis genes having a role in plant DNA repair were particularly studied and noted for their functional mapping. The functions observed to be overrepresented in the plant genome harbour DNA-3-methyladenine glycosylase activity, alkylbase DNA N-glycosylase activity and DNA-(apurinic or apyrimidinic site) lyase activity, suggesting their role in specialized functions such as gene regulation and DNA repair.

Protein Kinase Cι Drives a NOTCH3-dependent Stem-like Phenotype in Mutant KRAS Lung Adenocarcinoma.

PubMed

Ali, Syed A; Justilien, Verline; Jamieson, Lee; Murray, Nicole R; Fields, Alan P

2016-03-14

We report that the protein kinase Cι (PKCι) oncogene controls expression of NOTCH3, a key driver of stemness, in KRAS-mediated lung adenocarcinoma (LADC). PKCι activates NOTCH3 expression by phosphorylating the ELF3 transcription factor and driving ELF3 occupancy on the NOTCH3 promoter. PKCι-ELF3-NOTCH3 signaling controls the tumor-initiating cell phenotype by regulating asymmetric cell division, a process necessary for tumor initiation and maintenance. Primary LADC tumors exhibit PKCι-ELF3-NOTCH3 signaling, and combined pharmacologic blockade of PKCι and NOTCH synergistically inhibits tumorigenic behavior in vitro and LADC growth in vivo demonstrating the therapeutic potential of PKCι-ELF3-NOTCH3 signal inhibition to more effectively treat KRAS LADC. Copyright © 2016 Elsevier Inc. All rights reserved.

Polarized trafficking: the palmitoylation cycle distributes cytoplasmic proteins to distinct neuronal compartments.

PubMed

Tortosa, Elena; Hoogenraad, Casper C

2018-02-01

In neurons, polarized cargo distribution occurs mainly between the soma and axonal and dendritic compartments, and requires coordinated regulation of cytoskeletal remodeling and membrane trafficking. The Golgi complex plays a critical role during neuronal polarization and secretory trafficking has been shown to differentially transport proteins to both axons and dendrites. Besides the Golgi protein sorting, recent data revealed that palmitoylation cycles are an efficient mechanism to localize cytoplasmic, non-transmembrane proteins to particular neuronal compartments, such as the newly formed axon. Palmitoylation allows substrate proteins to bind to and ride with Golgi-derived secretory vesicles to all neuronal compartments. By allowing cytoplasmic proteins to 'hitchhike' on transport carriers in a non-polarized fashion, compartmentalized depalmitoylation may act as a selective retention mechanism. Copyright © 2018 Elsevier Ltd. All rights reserved.

The MHV68 M2 protein drives IL-10 dependent B cell proliferation and differentiation.

PubMed

Siegel, Andrea M; Herskowitz, Jeremy H; Speck, Samuel H

2008-04-04

Murine gammaherpesvirus 68 (MHV68) establishes long-term latency in memory B cells similar to the human gammaherpesvirus Epstein Barr Virus (EBV). EBV encodes an interleukin-10 (IL-10) homolog and modulates cellular IL-10 expression; however, the role of IL-10 in the establishment and/or maintenance of chronic EBV infection remains unclear. Notably, MHV68 does not encode an IL-10 homolog, but virus infection has been shown to result in elevated serum IL-10 levels in wild-type mice, and IL-10 deficiency results in decreased establishment of virus latency. Here we show that a unique MHV68 latency-associated gene product, the M2 protein, is required for the elevated serum IL-10 levels observed at 2 weeks post-infection. Furthermore, M2 protein expression in primary murine B cells drives high level IL-10 expression along with increased secretion of IL-2, IL-6, and MIP-1alpha. M2 expression was also shown to significantly augment LPS driven survival and proliferation of primary murine B cells. The latter was dependent on IL-10 expression as demonstrated by the failure of IL10-/- B cells to proliferate in response to M2 protein expression and rescue of M2-associated proliferation by addition of recombinant murine IL-10. M2 protein expression in primary B cells also led to upregulated surface expression of the high affinity IL-2 receptor (CD25) and the activation marker GL7, along with down-regulated surface expression of B220, MHC II, and sIgD. The cells retained CD19 and sIgG expression, suggesting differentiation to a pre-plasma memory B cell phenotype. These observations are consistent with previous analyses of M2-null MHV68 mutants that have suggested a role for the M2 protein in expansion and differentiation of MHV68 latently infected B cells-perhaps facilitating the establishment of virus latency in memory B cells. Thus, while the M2 protein is unique to MHV68, analysis of M2 function has revealed an important role for IL-10 in MHV68 pathogenesis-identifying a

Protein kinase D1 drives pancreatic acinar cell reprogramming and progression to intraepithelial neoplasia

NASA Astrophysics Data System (ADS)

Liou, Geou-Yarh; Döppler, Heike; Braun, Ursula B.; Panayiotou, Richard; Scotti Buzhardt, Michele; Radisky, Derek C.; Crawford, Howard C.; Fields, Alan P.; Murray, Nicole R.; Wang, Q. Jane; Leitges, Michael; Storz, Peter

2015-02-01

The transdifferentiation of pancreatic acinar cells to a ductal phenotype (acinar-to-ductal metaplasia, ADM) occurs after injury or inflammation of the pancreas and is a reversible process. However, in the presence of activating Kras mutations or persistent epidermal growth factor receptor (EGF-R) signalling, cells that underwent ADM can progress to pancreatic intraepithelial neoplasia (PanIN) and eventually pancreatic cancer. In transgenic animal models, ADM and PanINs are initiated by high-affinity ligands for EGF-R or activating Kras mutations, but the underlying signalling mechanisms are not well understood. Here, using a conditional knockout approach, we show that protein kinase D1 (PKD1) is sufficient to drive the reprogramming process to a ductal phenotype and progression to PanINs. Moreover, using 3D explant culture of primary pancreatic acinar cells, we show that PKD1 acts downstream of TGFα and Kras, to mediate formation of ductal structures through activation of the Notch pathway.

Extended driving impairs nocturnal driving performances.

PubMed

Sagaspe, Patricia; Taillard, Jacques; Akerstedt, Torbjorn; Bayon, Virginie; Espié, Stéphane; Chaumet, Guillaume; Bioulac, Bernard; Philip, Pierre

2008-01-01

Though fatigue and sleepiness at the wheel are well-known risk factors for traffic accidents, many drivers combine extended driving and sleep deprivation. Fatigue-related accidents occur mainly at night but there is no experimental data available to determine if the duration of prior driving affects driving performance at night. Participants drove in 3 nocturnal driving sessions (3-5 am, 1-5 am and 9 pm-5 am) on open highway. Fourteen young healthy men (mean age [+/-SD] = 23.4 [+/-1.7] years) participated Inappropriate line crossings (ILC) in the last hour of driving of each session, sleep variables, self-perceived fatigue and sleepiness were measured. Compared to the short (3-5 am) driving session, the incidence rate ratio of inappropriate line crossings increased by 2.6 (95% CI, 1.1 to 6.0; P<.05) for the intermediate (1-5 am) driving session and by 4.0 (CI, 1.7 to 9.4; P<.001) for the long (9 pm-5 am) driving session. Compared to the reference session (9-10 pm), the incidence rate ratio of inappropriate line crossings were 6.0 (95% CI, 2.3 to 15.5; P<.001), 15.4 (CI, 4.6 to 51.5; P<.001) and 24.3 (CI, 7.4 to 79.5; P<.001), respectively, for the three different durations of driving. Self-rated fatigue and sleepiness scores were both positively correlated to driving impairment in the intermediate and long duration sessions (P<.05) and increased significantly during the nocturnal driving sessions compared to the reference session (P<.01). At night, extended driving impairs driving performances and therefore should be limited.

Distribution of gluten proteins in bread wheat (Triticum aestivum) grain

PubMed Central

Tosi, Paola; Gritsch, Cristina Sanchis; He, Jibin; Shewry, Peter R.

2011-01-01

Background and Aims Gluten proteins are the major storage protein fraction in the mature wheat grain. They are restricted to the starchy endosperm, which forms white flour on milling, and interact during grain development to form large polymers which form a continuous proteinaceous network when flour is mixed with water to give dough. This network confers viscosity and elasticity to the dough, enabling the production of leavened products. The starchy endosperm is not a homogeneous tissue and quantitative and qualitative gradients exist for the major components: protein, starch and cell wall polysaccharides. Gradients in protein content and composition are the most evident and are of particular interest because of the major role played by the gluten proteins in determining grain processing quality. Methods Protein gradients in the starchy endosperm were investigated using antibodies for specific gluten protein types for immunolocalization in developing grains and for western blot analysis of protein extracts from flour fractions obtained by sequential abrasion (pearling) to prepare tissue layers. Key Results Differential patterns of distribution were found for the high-molecular-weight subunits of glutenin (HMW-GS) and γ-gliadins when compared with the low-molecular-weight subunits of glutenin (LMW-GS), ω- and α-gliadins. The first two types of gluten protein are more abundant in the inner endosperm layers and the latter more abundant in the subaleurone. Immunolocalization also showed that segregation of gluten proteins occurs both between and within protein bodies during protein deposition and may still be retained in the mature grain. Conclusions Quantitative and qualitative gradients in gluten protein composition are established during grain development. These gradients may be due to the origin of subaleurone cells, which unlike other starchy endosperm cells derive from the re-differentiation of aleurone cells, but could also result from the action of specific

A model of canopy photosynthesis incorporating protein distribution through the canopy and its acclimation to light, temperature and CO2

PubMed Central

Johnson, Ian R.; Thornley, John H. M.; Frantz, Jonathan M.; Bugbee, Bruce

2010-01-01

Background and Aims The distribution of photosynthetic enzymes, or nitrogen, through the canopy affects canopy photosynthesis, as well as plant quality and nitrogen demand. Most canopy photosynthesis models assume an exponential distribution of nitrogen, or protein, through the canopy, although this is rarely consistent with experimental observation. Previous optimization schemes to derive the nitrogen distribution through the canopy generally focus on the distribution of a fixed amount of total nitrogen, which fails to account for the variation in both the actual quantity of nitrogen in response to environmental conditions and the interaction of photosynthesis and respiration at similar levels of complexity. Model A model of canopy photosynthesis is presented for C3 and C4 canopies that considers a balanced approach between photosynthesis and respiration as well as plant carbon partitioning. Protein distribution is related to irradiance in the canopy by a flexible equation for which the exponential distribution is a special case. The model is designed to be simple to parameterize for crop, pasture and ecosystem studies. The amount and distribution of protein that maximizes canopy net photosynthesis is calculated. Key Results The optimum protein distribution is not exponential, but is quite linear near the top of the canopy, which is consistent with experimental observations. The overall concentration within the canopy is dependent on environmental conditions, including the distribution of direct and diffuse components of irradiance. Conclusions The widely used exponential distribution of nitrogen or protein through the canopy is generally inappropriate. The model derives the optimum distribution with characteristics that are consistent with observation, so overcoming limitations of using the exponential distribution. Although canopies may not always operate at an optimum, optimization analysis provides valuable insight into plant acclimation to environmental

Allowance for effects of thermodynamic nonideality in sedimentation equilibrium distributions reflecting protein dimerization.

PubMed

Wills, Peter R; Scott, David J; Winzor, Donald J

2012-03-01

This reexamination of a high-speed sedimentation equilibrium distribution for α-chymotrypsin under slightly acidic conditions (pH 4.1, I(M) 0.05) has provided experimental support for the adequacy of nearest-neighbor considerations in the allowance for effects of thermodynamic nonideality in the characterization of protein self-association over a moderate concentration range (up to 8 mg/mL). A widely held but previously untested notion about allowance for thermodynamic nonideality effects is thereby verified experimentally. However, it has also been shown that a greater obstacle to better characterization of protein self-association is likely to be the lack of a reliable estimate of monomer net charge, a parameter that has a far more profound effect on the magnitude of the measured equilibrium constant than any deficiency in current procedures for incorporating the effects of thermodynamic nonideality into the analysis of sedimentation equilibrium distributions reflecting reversible protein self-association. Copyright © 2011 Elsevier Inc. All rights reserved.

Fuel consumption for various driving styles in conventional and hybrid electric vehicles: Integrating driving cycle predictions with fuel consumption optimization

DOE PAGES

Rios-Torres, Jackeline; Liu, Jun; Khattak, Asad

2018-06-14

Here, improving fuel economy and lowering emissions are key societal goals. Standard driving cycles, pre-designed by the US Environmental Protection Agency (EPA), have long been used to estimate vehicle fuel economy in laboratory-controlled conditions. They have also been used to test and tune different energy management strategies for hybrid electric vehicles (HEVs). This paper aims to estimate fuel consumption for a conventional vehicle and a HEV using personalized driving cycles extracted from real-world data to study the effects of different driving styles and vehicle types on fuel consumption when compared to the estimates based on standard driving cycles. To domore » this, we extracted driving cycles for conventional vehicles and HEVs from a large-scale U.S. survey that contains real-world GPS-based driving records. Next, the driving cycles were assigned to one of three categories: volatile, normal, or calm. Then, the driving cycles were used along with a driver-vehicle simulation that captures driver decisions (vehicle speed during a trip), powertrain, and vehicle dynamics to estimate fuel consumption for conventional vehicles and HEVs with power-split powertrain. To further optimize fuel consumption for HEVs, the Equivalent Consumption Minimization Strategy (ECMS) is applied. The results show that depending on the driving style and the driving scenario, conventional vehicle fuel consumption can vary widely compared with standard EPA driving cycles. Specifically, conventional vehicle fuel consumption was 13% lower in calm urban driving, but almost 34% higher for volatile highway driving compared with standard EPA driving cycles. Interestingly, when a driving cycle is predicted based on the application of case-based reasoning and used to tune the power distribution in a hybrid electric vehicle, its fuel consumption can be reduced by up to 12% in urban driving. Implications and limitations of the findings are discussed.« less

Fuel consumption for various driving styles in conventional and hybrid electric vehicles: Integrating driving cycle predictions with fuel consumption optimization

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

Rios-Torres, Jackeline; Liu, Jun; Khattak, Asad

Here, improving fuel economy and lowering emissions are key societal goals. Standard driving cycles, pre-designed by the US Environmental Protection Agency (EPA), have long been used to estimate vehicle fuel economy in laboratory-controlled conditions. They have also been used to test and tune different energy management strategies for hybrid electric vehicles (HEVs). This paper aims to estimate fuel consumption for a conventional vehicle and a HEV using personalized driving cycles extracted from real-world data to study the effects of different driving styles and vehicle types on fuel consumption when compared to the estimates based on standard driving cycles. To domore » this, we extracted driving cycles for conventional vehicles and HEVs from a large-scale U.S. survey that contains real-world GPS-based driving records. Next, the driving cycles were assigned to one of three categories: volatile, normal, or calm. Then, the driving cycles were used along with a driver-vehicle simulation that captures driver decisions (vehicle speed during a trip), powertrain, and vehicle dynamics to estimate fuel consumption for conventional vehicles and HEVs with power-split powertrain. To further optimize fuel consumption for HEVs, the Equivalent Consumption Minimization Strategy (ECMS) is applied. The results show that depending on the driving style and the driving scenario, conventional vehicle fuel consumption can vary widely compared with standard EPA driving cycles. Specifically, conventional vehicle fuel consumption was 13% lower in calm urban driving, but almost 34% higher for volatile highway driving compared with standard EPA driving cycles. Interestingly, when a driving cycle is predicted based on the application of case-based reasoning and used to tune the power distribution in a hybrid electric vehicle, its fuel consumption can be reduced by up to 12% in urban driving. Implications and limitations of the findings are discussed.« less

Anisotropy of Crumbs and aPKC Drives Myosin Cable Assembly during Tube Formation

PubMed Central

Röper, Katja

2012-01-01

Summary The formation of tubular structures from epithelial sheets is a key process of organ formation in all animals, but the cytoskeletal rearrangements that cause the cell shape changes that drive tubulogenesis are not well understood. Using live imaging and super-resolution microscopy to analyze the tubulogenesis of the Drosophila salivary glands, I find that an anisotropic plasma membrane distribution of the protein Crumbs, mediated by its large extracellular domain, determines the subcellular localization of a supracellular actomyosin cable in the cells at the placode border, with myosin II accumulating at edges where Crumbs is lowest. Laser ablation shows that the cable is under increased tension, implying an active involvement in the invagination process. Crumbs anisotropy leads to anisotropic distribution of aPKC, which in turn can negatively regulate Rok, thus preventing the formation of a cable where Crumbs and aPKC are localized. PMID:23153493

Anisotropy of Crumbs and aPKC drives myosin cable assembly during tube formation.

PubMed

Röper, Katja

2012-11-13

The formation of tubular structures from epithelial sheets is a key process of organ formation in all animals, but the cytoskeletal rearrangements that cause the cell shape changes that drive tubulogenesis are not well understood. Using live imaging and super-resolution microscopy to analyze the tubulogenesis of the Drosophila salivary glands, I find that an anisotropic plasma membrane distribution of the protein Crumbs, mediated by its large extracellular domain, determines the subcellular localization of a supracellular actomyosin cable in the cells at the placode border, with myosin II accumulating at edges where Crumbs is lowest. Laser ablation shows that the cable is under increased tension, implying an active involvement in the invagination process. Crumbs anisotropy leads to anisotropic distribution of aPKC, which in turn can negatively regulate Rok, thus preventing the formation of a cable where Crumbs and aPKC are localized. Copyright © 2012 Elsevier Inc. All rights reserved.

Spatial gene drives and pushed genetic waves

PubMed Central

Tanaka, Hidenori; Stone, Howard A.; Nelson, David R.

2017-01-01

Gene drives have the potential to rapidly replace a harmful wild-type allele with a gene drive allele engineered to have desired functionalities. However, an accidental or premature release of a gene drive construct to the natural environment could damage an ecosystem irreversibly. Thus, it is important to understand the spatiotemporal consequences of the super-Mendelian population genetics before potential applications. Here, we use a reaction–diffusion model for sexually reproducing diploid organisms to study how a locally introduced gene drive allele spreads to replace the wild-type allele, although it possesses a selective disadvantage s > 0. Using methods developed by Barton and collaborators, we show that socially responsible gene drives require 0.5 < s < 0.697, a rather narrow range. In this “pushed wave” regime, the spatial spreading of gene drives will be initiated only when the initial frequency distribution is above a threshold profile called “critical propagule,” which acts as a safeguard against accidental release. We also study how the spatial spread of the pushed wave can be stopped by making gene drives uniquely vulnerable (“sensitizing drive”) in a way that is harmless for a wild-type allele. Finally, we show that appropriately sensitized drives in two dimensions can be stopped, even by imperfect barriers perforated by a series of gaps. PMID:28743753

Expected distributions of root-mean-square positional deviations in proteins.

PubMed

Pitera, Jed W

2014-06-19

The atom positional root-mean-square deviation (RMSD) is a standard tool for comparing the similarity of two molecular structures. It is used to characterize the quality of biomolecular simulations, to cluster conformations, and as a reaction coordinate for conformational changes. This work presents an approximate analytic form for the expected distribution of RMSD values for a protein or polymer fluctuating about a stable native structure. The mean and maximum of the expected distribution are independent of chain length for long chains and linearly proportional to the average atom positional root-mean-square fluctuations (RMSF). To approximate the RMSD distribution for random-coil or unfolded ensembles, numerical distributions of RMSD were generated for ensembles of self-avoiding and non-self-avoiding random walks. In both cases, for all reference structures tested for chains more than three monomers long, the distributions have a maximum distant from the origin with a power-law dependence on chain length. The purely entropic nature of this result implies that care must be taken when interpreting stable high-RMSD regions of the free-energy landscape as "intermediates" or well-defined stable states.

Driving comfort, enjoyment and acceptance of automated driving - effects of drivers' age and driving style familiarity.

PubMed

Hartwich, Franziska; Beggiato, Matthias; Krems, Josef F

2018-02-23

Automated driving has the potential to improve the safety and efficiency of future traffic and to extend elderly peoples' driving life, provided it is perceived as comfortable and joyful and is accepted by drivers. Driving comfort could be enhanced by familiar automated driving styles based on drivers' manual driving styles. In a two-stage driving simulator study, effects of driving automation and driving style familiarity on driving comfort, enjoyment and system acceptance were examined. Twenty younger and 20 older drivers performed a manual and four automated drives of different driving style familiarity. Acceptance, comfort and enjoyment were assessed after driving with standardised questionnaires, discomfort during driving via handset control. Automation increased both age groups' comfort, but decreased younger drivers' enjoyment. Younger drivers showed higher comfort, enjoyment and acceptance with familiar automated driving styles, whereas older drivers preferred unfamiliar, automated driving styles tending to be faster than their age-affected manual driving styles. Practitioner Summary: Automated driving needs to be comfortable and enjoyable to be accepted by drivers, which could be enhanced by driving style individualisation. This approach was evaluated in a two-stage driving simulator study for different age groups. Younger drivers preferred familiar driving styles, whereas older drivers preferred driving styles unaffected by age.

Membrane-Mediated Cooperativity of Proteins

NASA Astrophysics Data System (ADS)

Weikl, Thomas R.

2018-04-01

Besides direct protein-protein interactions, indirect interactions mediated by membranes play an important role for the assembly and cooperative function of proteins in membrane shaping and adhesion. The intricate shapes of biological membranes are generated by proteins that locally induce membrane curvature. Indirect curvature-mediated interactions between these proteins arise because the proteins jointly affect the bending energy of the membranes. These curvature-mediated interactions are attractive for crescent-shaped proteins and are a driving force in the assembly of the proteins during membrane tubulation. Membrane adhesion results from the binding of receptor and ligand proteins that are anchored in the apposing membranes. The binding of these proteins strongly depends on nanoscale shape fluctuations of the membranes, leading to a fluctuation-mediated binding cooperativity. A length mismatch between receptor-ligand complexes in membrane adhesion zones causes repulsive curvature-mediated interactions that are a driving force for the length-based segregation of proteins during membrane adhesion.

Distribution of Animal Drugs among Curd, Whey, and Milk Protein Fractions in Spiked Skim Milk and Whey.

PubMed

Shappell, Nancy W; Shelver, Weilin L; Lupton, Sara J; Fanaselle, Wendy; Van Doren, Jane M; Hakk, Heldur

2017-02-01

It is important to understand the partitioning of drugs in processed milk and milk products, when drugs are present in raw milk, in order to estimate the potential consumer exposure. Radioisotopically labeled erythromycin, ivermectin, ketoprofen, oxytetracycline, penicillin G, sulfadimethoxine, and thiabendazole were used to evaluate the distribution of animal drugs among rennet curd, whey, and protein fractions from skim cow milk. Our previous work reported the distribution of these same drugs between skim and fat fractions of milk. Drug distribution between curd and whey was significantly correlated (R 2 = 0.70) to the drug's lipophilicity (log P), with improved correlation using log D (R 2 = 0.95). Distribution of drugs was concentration independent over the range tested (20-2000 nM). With the exception of thiabendazole and ivermectin, more drug was associated with whey protein than casein on a nmol/g protein basis (oxytetracycline experiment not performed). These results provide insights into the distribution of animal drug residues, if present in cow milk, among milk fractions, with possible extrapolation to milk products.

Distribution of tubulin, kinesin, and dynein in light- and dark-adapted octopus retinas.

PubMed

Martinez, J M; Elfarissi, H; De Velasco, B; Ochoa, G H; Miller, A M; Clark, Y M; Matsumoto, B; Robles, L J

2000-01-01

Cephalopod retinas exhibit several responses to light and dark adaptation, including rhabdom size changes, photopigment movements, and pigment granule migration. Light- and dark-directed rearrangements of microfilament and microtubule cytoskeletal transport pathways could drive these changes. Recently, we localized actin-binding proteins in light-/dark-adapted octopus rhabdoms and suggested that actin cytoskeletal rearrangements bring about the formation and degradation of rhabdomere microvilli subsets. To determine if the microtubule cytoskeleton and associated motor proteins control the other light/dark changes, we used immunoblotting and immunocytochemical procedures to map the distribution of tubulin, kinesin, and dynein in dorsal and ventral halves of light- and dark-adapted octopus retinas. Immunoblots detected alpha- and beta-tubulin, dynein intermediate chain, and kinesin heavy chain in extracts of whole retinas. Epifluorescence and confocal microscopy showed that the tubulin proteins were distributed throughout the retina with more immunoreactivity in retinas exposed to light. Kinesin localization was heavy in the pigment layer of light- and dark-adapted ventral retinas but was less prominent in the dorsal region. Dynein distribution also varied in dorsal and ventral retinas with more immunoreactivity in light- and dark-adapted ventral retinas and confocal microscopy emphasized the granular nature of this labeling. We suggest that light may regulate the distribution of microtubule cytoskeletal proteins in the octopus retina and that position, dorsal versus ventral, also influences the distribution of motor proteins. The microtubule cytoskeleton is most likely involved in pigment granule migration in the light and dark and with the movement of transport vesicles from the photoreceptor inner segments to the rhabdoms.

Description of atomic burials in compact globular proteins by Fermi-Dirac probability distributions.

PubMed

Gomes, Antonio L C; de Rezende, Júlia R; Pereira de Araújo, Antônio F; Shakhnovich, Eugene I

2007-02-01

We perform a statistical analysis of atomic distributions as a function of the distance R from the molecular geometrical center in a nonredundant set of compact globular proteins. The number of atoms increases quadratically for small R, indicating a constant average density inside the core, reaches a maximum at a size-dependent distance R(max), and falls rapidly for larger R. The empirical curves turn out to be consistent with the volume increase of spherical concentric solid shells and a Fermi-Dirac distribution in which the distance R plays the role of an effective atomic energy epsilon(R) = R. The effective chemical potential mu governing the distribution increases with the number of residues, reflecting the size of the protein globule, while the temperature parameter beta decreases. Interestingly, betamu is not as strongly dependent on protein size and appears to be tuned to maintain approximately half of the atoms in the high density interior and the other half in the exterior region of rapidly decreasing density. A normalized size-independent distribution was obtained for the atomic probability as a function of the reduced distance, r = R/R(g), where R(g) is the radius of gyration. The global normalized Fermi distribution, F(r), can be reasonably decomposed in Fermi-like subdistributions for different atomic types tau, F(tau)(r), with Sigma(tau)F(tau)(r) = F(r), which depend on two additional parameters mu(tau) and h(tau). The chemical potential mu(tau) affects a scaling prefactor and depends on the overall frequency of the corresponding atomic type, while the maximum position of the subdistribution is determined by h(tau), which appears in a type-dependent atomic effective energy, epsilon(tau)(r) = h(tau)r, and is strongly correlated to available hydrophobicity scales. Better adjustments are obtained when the effective energy is not assumed to be necessarily linear, or epsilon(tau)*(r) = h(tau)*r(alpha,), in which case a correlation with hydrophobicity

Predicting drowsy driving in real-time situations: Using an advanced driving simulator, accelerated failure time model, and virtual location-based services.

PubMed

Wang, Junhua; Sun, Shuaiyi; Fang, Shouen; Fu, Ting; Stipancic, Joshua

2017-02-01

This paper aims to both identify the factors affecting driver drowsiness and to develop a real-time drowsy driving probability model based on virtual Location-Based Services (LBS) data obtained using a driving simulator. A driving simulation experiment was designed and conducted using 32 participant drivers. Collected data included the continuous driving time before detection of drowsiness and virtual LBS data related to temperature, time of day, lane width, average travel speed, driving time in heavy traffic, and driving time on different roadway types. Demographic information, such as nap habit, age, gender, and driving experience was also collected through questionnaires distributed to the participants. An Accelerated Failure Time (AFT) model was developed to estimate the driving time before detection of drowsiness. The results of the AFT model showed driving time before drowsiness was longer during the day than at night, and was longer at lower temperatures. Additionally, drivers who identified as having a nap habit were more vulnerable to drowsiness. Generally, higher average travel speeds were correlated to a higher risk of drowsy driving, as were longer periods of low-speed driving in traffic jam conditions. Considering different road types, drivers felt drowsy more quickly on freeways compared to other facilities. The proposed model provides a better understanding of how driver drowsiness is influenced by different environmental and demographic factors. The model can be used to provide real-time data for the LBS-based drowsy driving warning system, improving past methods based only on a fixed driving. Copyright © 2016 Elsevier Ltd. All rights reserved.

Glaucoma and Driving: On-Road Driving Characteristics

PubMed Central

Wood, Joanne M.; Black, Alex A.; Mallon, Kerry; Thomas, Ravi; Owsley, Cynthia

2016-01-01

Purpose To comprehensively investigate the types of driving errors and locations that are most problematic for older drivers with glaucoma compared to those without glaucoma using a standardized on-road assessment. Methods Participants included 75 drivers with glaucoma (mean = 73.2±6.0 years) with mild to moderate field loss (better-eye MD = -1.21 dB; worse-eye MD = -7.75 dB) and 70 age-matched controls without glaucoma (mean = 72.6 ± 5.0 years). On-road driving performance was assessed in a dual-brake vehicle by an occupational therapist using a standardized scoring system which assessed the types of driving errors and the locations where they were made and the number of critical errors that required an instructor intervention. Driving safety was rated on a 10-point scale. Self-reported driving ability and difficulties were recorded using the Driving Habits Questionnaire. Results Drivers with glaucoma were rated as significantly less safe, made more driving errors, and had almost double the rate of critical errors than those without glaucoma. Driving errors involved lane positioning and planning/approach, and were significantly more likely to occur at traffic lights and yield/give-way intersections. There were few between group differences in self-reported driving ability. Conclusions Older drivers with glaucoma with even mild to moderate field loss exhibit impairments in driving ability, particularly during complex driving situations that involve tactical problems with lane-position, planning ahead and observation. These results, together with the fact that these drivers self-report their driving to be relatively good, reinforce the need for evidence-based on-road assessments for evaluating driving fitness. PMID:27472221

Glaucoma and Driving: On-Road Driving Characteristics.

PubMed

Wood, Joanne M; Black, Alex A; Mallon, Kerry; Thomas, Ravi; Owsley, Cynthia

2016-01-01

To comprehensively investigate the types of driving errors and locations that are most problematic for older drivers with glaucoma compared to those without glaucoma using a standardized on-road assessment. Participants included 75 drivers with glaucoma (mean = 73.2±6.0 years) with mild to moderate field loss (better-eye MD = -1.21 dB; worse-eye MD = -7.75 dB) and 70 age-matched controls without glaucoma (mean = 72.6 ± 5.0 years). On-road driving performance was assessed in a dual-brake vehicle by an occupational therapist using a standardized scoring system which assessed the types of driving errors and the locations where they were made and the number of critical errors that required an instructor intervention. Driving safety was rated on a 10-point scale. Self-reported driving ability and difficulties were recorded using the Driving Habits Questionnaire. Drivers with glaucoma were rated as significantly less safe, made more driving errors, and had almost double the rate of critical errors than those without glaucoma. Driving errors involved lane positioning and planning/approach, and were significantly more likely to occur at traffic lights and yield/give-way intersections. There were few between group differences in self-reported driving ability. Older drivers with glaucoma with even mild to moderate field loss exhibit impairments in driving ability, particularly during complex driving situations that involve tactical problems with lane-position, planning ahead and observation. These results, together with the fact that these drivers self-report their driving to be relatively good, reinforce the need for evidence-based on-road assessments for evaluating driving fitness.

Finite driving rate and anisotropy effects in landslide modeling

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

Piegari, E.; Cataudella, V.; Di Maio, R.

2006-02-15

In order to characterize landslide frequency-size distributions and individuate hazard scenarios and their possible precursors, we investigate a cellular automaton where the effects of a finite driving rate and the anisotropy are taken into account. The model is able to reproduce observed features of landslide events, such as power-law distributions, as experimentally reported. We analyze the key role of the driving rate and show that, as it is increased, a crossover from power-law to non-power-law behaviors occurs. Finally, a systematic investigation of the model on varying its anisotropy factors is performed and the full diagram of its dynamical behaviors ismore » presented.« less

Centromeres Drive a Hard Bargain

PubMed Central

Rosin, Leah F.; Mellone, Barbara G.

2017-01-01

Centromeres are essential chromosomal structures that mediate the accurate distribution of genetic material during meiotic and mitotic cell divisions. In most organisms, centromeres are epigenetically specified and propagated by nucleosomes containing the centromere-specific H3 variant, CENP-A. Although centromeres perform a critical and conserved function, CENP-A and the underlying centromeric DNA are rapidly evolving. This paradox has been explained by the centromere drive hypothesis, which proposes that CENP-A is undergoing an evolutionary tug-of-war with selfish centromeric DNA. Here, we review our current understanding of CENP-A evolution in relation to centromere drive and discuss classical and recent advances, including new evidence implicating CENP-A chaperones in this conflict. PMID:28069312

mTORC1-dependent translation of collapsin response mediator protein-2 drives neuroadaptations underlying excessive alcohol-drinking behaviors

PubMed Central

Liu, F; Laguesse, S; Legastelois, R; Morisot, N; Ben Hamida, S; Ron, D

2017-01-01

Mammalian target of rapamycin complex 1 (mTORC1) has an essential role in dendritic mRNA translation and participates in mechanisms underlying alcohol-drinking and reconsolidation of alcohol-related memories. Here, we report that excessive alcohol consumption increases the translation of downstream targets of mTORC1, including collapsin response mediator protein-2 (CRMP-2), in the nucleus accumbens (NAc) of rodents. We show that alcohol-mediated induction of CRMP-2 translation is mTORC1-dependent, leading to increased CRMP-2 protein levels. Furthermore, we demonstrate that alcohol intake also blocks glycogen synthase kinase-3β (GSK-3β)-phosphorylation of CRMP-2, which results in elevated binding of CRMP-2 to microtubules and a concomitant increase in microtubule content. Finally, we show that systemic administration of the CRMP-2 inhibitor lacosamide, or knockdown of CRMP-2 in the NAc decreases excessive alcohol intake. These results suggest that CRMP-2 in the NAc is a convergent point that receives inputs from two signaling pathways, mTORC1 and GSK-3β, that in turn drives excessive alcohol-drinking behaviors. PMID:26952865

Asynchronous Cholinergic Drive Correlates with Excitation-Inhibition Imbalance via a Neuronal Ca2+ Sensor Protein.

PubMed

Zhou, Keming; Cherra, Salvatore J; Goncharov, Alexandr; Jin, Yishi

2017-05-09

Excitation-inhibition imbalance in neural networks is widely linked to neurological and neuropsychiatric disorders. However, how genetic factors alter neuronal activity, leading to excitation-inhibition imbalance, remains unclear. Here, using the C. elegans locomotor circuit, we examine how altering neuronal activity for varying time periods affects synaptic release pattern and animal behavior. We show that while short-duration activation of excitatory cholinergic neurons elicits a reversible enhancement of presynaptic strength, persistent activation results to asynchronous and reduced cholinergic drive, inducing imbalance between endogenous excitation and inhibition. We find that the neuronal calcium sensor protein NCS-2 is required for asynchronous cholinergic release in an activity-dependent manner and dampens excitability of inhibitory neurons non-cell autonomously. The function of NCS-2 requires its Ca 2+ binding and membrane association domains. These results reveal a synaptic mechanism implicating asynchronous release in regulation of excitation-inhibition balance. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Effects of trait anger, driving anger, and driving experience on dangerous driving behavior: A moderated mediation analysis.

PubMed

Ge, Yan; Zhang, Qian; Zhao, Wenguo; Zhang, Kan; Qu, Weina

2017-11-01

To explore the effect of anger behind the wheel on driving behavior and accident involvement has been the subject of many studies. However, few studies have explored the interaction between anger and driving experience on dangerous driving behavior. This study is a moderated mediation analysis of the effect of trait anger, driving anger, and driving experience on driving behavior. A sample of 303 drivers was tested using the Trait Anger Scale (TAS), the Driving Anger Scale (DAS), and the Dula Dangerous Driving Index (DDDI). The results showed that trait anger and driving anger were positively correlated with dangerous driving behavior. Driving anger partially mediated the effect of trait anger on dangerous driving behavior. Driving experience moderated the relationship between trait anger and driving anger. It also moderated the effect of driving anger on dangerous driving behavior. These results suggest that drivers with more driving experience may be safer as they are not easily irritated during driving. © 2017 Wiley Periodicals, Inc.

Rational design of crystal contact-free space in protein crystals for analyzing spatial distribution of motions within protein molecules.

PubMed

Matsuoka, Rei; Shimada, Atsushi; Komuro, Yasuaki; Sugita, Yuji; Kohda, Daisuke

2016-03-01

Contacts with neighboring molecules in protein crystals inevitably restrict the internal motions of intrinsically flexible proteins. The resultant clear electron densities permit model building, as crystallographic snapshot structures. Although these still images are informative, they could provide biased pictures of the protein motions. If the mobile parts are located at a site lacking direct contacts in rationally designed crystals, then the amplitude of the movements can be experimentally analyzed. We propose a fusion protein method, to create crystal contact-free space (CCFS) in protein crystals and to place the mobile parts in the CCFS. Conventional model building fails when large amplitude motions exist. In this study, the mobile parts appear as smeared electron densities in the CCFS, by suitable processing of the X-ray diffraction data. We applied the CCFS method to a highly mobile presequence peptide bound to the mitochondrial import receptor, Tom20, and a catalytically relevant flexible segment in the oligosaccharyltransferase, AglB. These two examples demonstrated the general applicability of the CCFS method to the analysis of the spatial distribution of motions within protein molecules. © 2016 The Protein Society.

Distribution of syndecan-1 protein in developing mouse teeth

PubMed Central

Filatova, Anna; Pagella, Pierfrancesco; Mitsiadis, Thimios A.

2014-01-01

Syndecan-1 is a cell surface proteoglycan involved in the regulation of various biological processes such as proliferation, migration, condensation and differentiation of cells, intercellular communication, and morphogenesis. The extracellular domain of syndecan-1 can bind to extracellular matrix components and signaling molecules, while its intracellular domain interacts with cytoskeletal proteins, thus allowing the transfer of information about extracellular environment changes into the cell that consequently affect cellular behavior. Although previous studies have shown syndecan-1 expression during precise stages of tooth development, there is no equivalent study regrouping the expression patterns of syndecan-1 during all stages of odontogenesis. Here we examined the distribution of syndecan-1 protein in embryonic and post-natal developing mouse molars and incisors. Syndecan-1 distribution in mesenchymal tissues such as dental papilla and dental follicle was correlated with proliferating events and its expression was often linked to stem cell niche territories. Syndecan-1 was also expressed in mesenchymal cells that will differentiate into the dentin producing odontoblasts, but not in differentiated functional odontoblasts. In the epithelium, syndecan-1 was detected in all cell layers, by the exception of differentiated ameloblasts that form the enamel. Furthermore, syndecan-1 was expressed in osteoblast precursors and osteoclasts of the alveolar bone that surrounds the developing tooth germs. Taken together these results show the dynamic nature of syndecan-1 expression during odontogenesis and suggest its implication in various processes of tooth development and homeostasis. PMID:25642191

Extreme deconstruction supports niche conservatism driving New World bird diversity

NASA Astrophysics Data System (ADS)

Diniz-Filho, José Alexandre Felizola; Rangel, Thiago Fernando; dos Santos, Mariana Rocha

2012-08-01

It is expected that if environment fully establishes the borders of species geographic distribution, then richness patterns will arise simple by changing parameters on how environment affect each of the species. However, if other mechanisms (i.e., non-equilibrium of species' distributions with climate and historical contingency, shifts in adaptive peaks or biotic interactions) are driving species geographic distribution, models for species distribution and richness will not entirely match. Here we used the extreme deconstruction principle to test how niche conservatism keeping species geographic distributions in certain parts of environmental space drives richness patterns in New World birds, under tropical niche conservatism. Eight environmental variables were used to model the geographic distribution of 2790 species within 28 bird families using a GLM. Spatial patterns in richness for each of these families were also modeled as a function of these same variables using a standard OLS regression. Fit of these two types of models (mean MacFadden's ρ2 for GLM and R2 of OLS) across families and the match between GLM and OLS standardized slopes within and among bird families were then compared. We found a positive and significant correlation between GLM and OLS model fit (r = 0.601; P < 0.01), indicating that when environment strongly determine richness of a family, it also explains its species geographic distributions. The match between GLM and OLS slopes is significantly correlated with families' phylogenetic root distance (r = -0.467; P = 0.012), so that more basal families tend to have a better match between environmental drivers of richness and geographic distribution models. This is expected under tropical niche conservatism model and provides an integrated explanation on how processes at a lower hierarchical level (species' geographic distribution) drive diversity patterns.

Lubricant distribution and its effect on slider air bearing performance over bit patterned media disk of disk drives

NASA Astrophysics Data System (ADS)

Wu, Lin

2011-04-01

The distribution dynamics of a thin lubricant film on a bit-patterned media disk and its effect on the performance of the ultralow flying air bearing slider of disk drives are studied by direct numerical simulations. Our analysis shows that the physics governing lubricant distribution dynamics changes when deep enough sub-100-nm nanostructures are patterned on the disk surface. Air shearing under the slider that dominates lubricant flow on a flat disk may become negligible on a bit-patterned media disk. Surface tension and disjoining pressure become dominant factors instead. Our results show that disks with nanoscale patterns/roughness may no longer be treated as flat, and the air bearing load may strongly depend not only on the geometric detail of disk patterns but also on how lubricants are distributed on the patterns when slider-disk clearance is reduced to sub-10-nm. Air bearing load and consequently the slider's flying attitude are affected by disk pattern geometry, average lubricant thickness, and material properties of lubricant such as the surface tension coefficient and Hamaker constant. The significantly expanded parameter space, upon which ultralow flying slider's dynamics depends, has to be seriously considered in evaluating the head/disk interface tribology performance of next generation patterned media magnetic recording systems.

Self-rated Driving and Driving Safety in Older Adults

PubMed Central

Ross, Lesley A.; Dodson, Joan; Edwards, Jerri D.; Ackerman, Michelle L.; Ball, Karlene

2012-01-01

Many U.S. states rely on older adults to self-regulate their driving and determine when driving is no longer a safe option. However, the relationship of older adults’ self-rated driving in terms of actual driving competency outcomes is unclear. The current study investigates self-rated driving in terms of (1) systematic differences between older adults with high (good/excellent) versus low (poor/fair/average) self-ratings, and (2) the predictive nature of self-rated driving to adverse driving outcomes in older drivers (n=350; mean age 73.9, SD=5.25, range 65–91). Adverse driving outcomes included self-reported incidences of (1) being pulled over by the police, (2) receiving a citation, (3) receiving a recommendation to cease or limit driving, (4) crashes, and (5) state-reported crashes. Results found that older drivers with low self-ratings reported more medical conditions, less driving frequency, and had been given more suggestions to stop/limit their driving; there were no other significant differences between low and high self-raters. Logistic regression revealed older drivers were more likely to have a state-reported crash and receive a suggestion to stop or limit driving. Men were more likely to report all adverse driving outcomes except for receiving a suggestion to stop or limit driving. Regarding self-rated driving, older adults with high ratings were 66% less likely (OR=0.34, 95% CI=0.14–0.85) to have received suggestions to limit or stop driving after accounting for demographics, health and driving frequency. Self-ratings were not predictive of other driving outcomes (being pulled over by the police, receiving a citation, self-reported crashes, or state-reported crashes, ps>.05). Most older drivers (85.14%) rated themselves as either good or excellent drivers regardless of their actual previous citation or crash rates. Self-rated driving is likely not related to actual driving proficiency as indicated by previous crash involvement in older adults

Role of Transbilayer Distribution of Lipid Molecules on the Structure and Protein-Lipid Interaction of an Amyloidogenic Protein on the Membrane Surface

NASA Astrophysics Data System (ADS)

Cheng, Kwan; Cheng, Sara

We used molecular dynamics simulations to examine the effects of transbilayer distribution of lipid molecules, particularly anionic lipids with negatively charged headgroups, on the structure and binding kinetics of an amyloidogenic protein on the membrane surface and subsequent protein-induced structural disruption of the membrane. Our systems consisted of a model beta-sheet rich dimeric protein absorbed on asymmetric bilayers with neutral and anionic lipids and symmetric bilayers with neutral lipids. We observed larger folding, domain aggregation, and tilt angle of the absorbed protein on the asymmetric bilayer surfaces. We also detected more focused bilayer thinning in the asymmetric bilayer due to weak lipid-protein interactions. Our results support the mechanism that the higher lipid packing in the protein-contacting lipid leaflet promotes stronger protein-protein but weaker protein-lipid interactions of an amyloidogenic protein on the membrane surface. We speculate that the observed surface-induced structural and protein-lipid interaction of our model amyloidogenic protein may play a role in the early membrane-associated amyloid cascade pathway that leads to membrane structural damage of neurons in Alzheimer's disease. NSF ACI-1531594.

Distribution of Spiked Drugs between Milk Fat, Skim Milk, Whey, Curd, and Milk Protein Fractions: Expansion of Partitioning Models.

PubMed

Lupton, Sara J; Shappell, Nancy W; Shelver, Weilin L; Hakk, Heldur

2018-01-10

The distributions of eight drugs (acetaminophen, acetylsalicylic acid/salicylic acid, ciprofloxacin, clarithromycin, flunixin, phenylbutazone, praziquantel, and thiamphenicol) were determined in milk products (skim milk, milk fat, curd, whey, and whey protein) and used to expand a previous model (from 7 drugs to 15 drugs) for predicting drug distribution. Phenylbutazone and praziquantel were found to distribute with the lipid and curd phases (≥50%). Flunixin distribution was lower but similar in direction (12% in milk fat, 39% in curd). Acetaminophen, ciprofloxacin, and praziquantel preferentially associated with casein proteins, whereas thiamphenicol and clarithromycin associated preferentially to whey proteins. Regression analyses for log [milk fat]/[skim milk] and log [curd]/[whey] had r 2 values of 0.63 and 0.67, respectively, with p of <0.001 for 15 drugs (7 previously tested and 8 currently tested). The robustness of the distribution model was enhanced by doubling the number of drugs originally tested.

The distribution and query systems of the RCSB Protein Data Bank

PubMed Central

Bourne, Philip E.; Addess, Kenneth J.; Bluhm, Wolfgang F.; Chen, Li; Deshpande, Nita; Feng, Zukang; Fleri, Ward; Green, Rachel; Merino-Ott, Jeffrey C.; Townsend-Merino, Wayne; Weissig, Helge; Westbrook, John; Berman, Helen M.

2004-01-01

The Protein Data Bank (PDB; http://www.pdb.org) is the primary source of information on the 3D structure of biological macromolecules. The PDB’s mandate is to disseminate this information in the most usable form and as widely as possible. The current query and distribution system is described and an alpha version of the future re-engineered system introduced. PMID:14681399

Cerebral oscillatory activity during simulated driving using MEG.

PubMed

Sakihara, Kotoe; Hirata, Masayuki; Ebe, Kazutoshi; Kimura, Kenji; Yi Ryu, Seong; Kono, Yoshiyuki; Muto, Nozomi; Yoshioka, Masako; Yoshimine, Toshiki; Yorifuji, Shiro

2014-01-01

We aimed to examine cerebral oscillatory differences associated with psychological processes during simulated car driving. We recorded neuromagnetic signals in 14 healthy volunteers using magnetoencephalography (MEG) during simulated driving. MEG data were analyzed using synthetic aperture magnetometry to detect the spatial distribution of cerebral oscillations. Group effects between subjects were analyzed statistically using a non-parametric permutation test. Oscillatory differences were calculated by comparison between "passive viewing" and "active driving." "Passive viewing" was the baseline, and oscillatory differences during "active driving" showed an increase or decrease in comparison with a baseline. Power increase in the theta band was detected in the superior frontal gyrus (SFG) during active driving. Power decreases in the alpha, beta, and low gamma bands were detected in the right inferior parietal lobe (IPL), left postcentral gyrus (PoCG), middle temporal gyrus (MTG), and posterior cingulate gyrus (PCiG) during active driving. Power increase in the theta band in the SFG may play a role in attention. Power decrease in the right IPL may reflect selectively divided attention and visuospatial processing, whereas that in the left PoCG reflects sensorimotor activation related to driving manipulation. Power decreases in the MTG and PCiG may be associated with object recognition.

Hydration water and bulk water in proteins have distinct properties in radial distributions calculated from 105 atomic resolution crystal structures.

PubMed

Chen, Xianfeng; Weber, Irene; Harrison, Robert W

2008-09-25

Water plays a critical role in the structure and function of proteins, although the experimental properties of water around protein structures are not well understood. The water can be classified by the separation from the protein surface into bulk water and hydration water. Hydration water interacts closely with the protein and contributes to protein folding, stability, and dynamics, as well as interacting with the bulk water. Water potential functions are often parametrized to fit bulk water properties because of the limited experimental data for hydration water. Therefore, the structural and energetic properties of the hydration water were assessed for 105 atomic resolution (protein crystal structures with a high level of hydration water by calculating the experimental water-protein radial distribution function or surface distribution function (SDF) and water radial distribution function (RDF). Two maxima are observed in SDF: the first maximum at a radius of 2.75 A reflects first shell and hydrogen bond interactions between protein and water, and the second maximum at 3.65 A reflects second shell and van der Waals interactions between water and nonpolar atoms of protein-forming clathrate-hydrate-like structures. Thus, the two shells do not overlap. The RDF showed the features of liquid water rather than solid ice. The first and second maxima of RDF at 2.75 and 4.5 A, respectively, are the same as for bulk water, but the peaks are sharper, indicating hydration water is more stable than bulk water. Both distribution functions are inversely correlated with the distribution of B factors (atomic thermal factors) for the waters, suggesting that the maxima reflect stable positions. Therefore, the average water structure near the protein surface has experimentally observable differences from bulk water. This analysis will help improve the accuracy for models of water on the protein surface by providing rigorous data for the effects of the apparent chemical

The Lymphocytic Choriomeningitis Virus Matrix Protein PPXY Late Domain Drives the Production of Defective Interfering Particles

PubMed Central

Ziegler, Christopher M.; Eisenhauer, Philip; Bruce, Emily A.; Weir, Marion E.; King, Benjamin R.; Klaus, Joseph P.; Krementsov, Dimitry N.; Shirley, David J.; Ballif, Bryan A.; Botten, Jason

2016-01-01

Arenaviruses cause severe diseases in humans but establish asymptomatic, lifelong infections in rodent reservoirs. Persistently-infected rodents harbor high levels of defective interfering (DI) particles, which are thought to be important for establishing persistence and mitigating virus-induced cytopathic effect. Little is known about what drives the production of DI particles. We show that neither the PPXY late domain encoded within the lymphocytic choriomeningitis virus (LCMV) matrix protein nor a functional endosomal sorting complex transport (ESCRT) pathway is absolutely required for the generation of standard infectious virus particles. In contrast, DI particle release critically requires the PPXY late domain and is ESCRT-dependent. Additionally, the terminal tyrosine in the PPXY motif is reversibly phosphorylated and our findings indicate that this posttranslational modification may regulate DI particle formation. Thus we have uncovered a new role for the PPXY late domain and a possible mechanism for its regulation. PMID:27010636

Stability enhancement and fuel economy of the 4-wheel-drive hybrid electric vehicles by optimal tyre force distribution

NASA Astrophysics Data System (ADS)

Goodarzi, Avesta; Mohammadi, Masoud

2014-04-01

In this paper, vehicle stability control and fuel economy for a 4-wheel-drive hybrid vehicle are investigated. The integrated controller is designed within three layers. The first layer determines the total yaw moment and total lateral force made by using an optimal controller method to follow the desired dynamic behaviour of a vehicle. The second layer determines optimum tyre force distribution in order to optimise tyre usage and find out how the tyres should share longitudinal and lateral forces to achieve a target vehicle response under the assumption that all four wheels can be independently steered, driven, and braked. In the third layer, the active steering, wheel slip, and electrical motor torque controllers are designed. In the front axle, internal combustion engine (ICE) is coupled to an electric motor (EM). The control strategy has to determine the power distribution between ICE and EM to minimise fuel consumption and allowing the vehicle to be charge sustaining. Finally, simulations performed in MATLAB/SIMULINK environment show that the proposed structure could enhance the vehicle stability and fuel economy in different manoeuvres.

Self-rated driving and driving safety in older adults.

PubMed

Ross, Lesley A; Dodson, Joan E; Edwards, Jerri D; Ackerman, Michelle L; Ball, Karlene

2012-09-01

Many U.S. states rely on older adults to self-regulate their driving and determine when driving is no longer a safe option. However, the relationship of older adults' self-rated driving in terms of actual driving competency outcomes is unclear. The current study investigates self-rated driving in terms of (1) systematic differences between older adults with high (good/excellent) versus low (poor/fair/average) self-ratings, and (2) the predictive nature of self-rated driving to adverse driving outcomes in older adults (n=350; mean age 73.9, SD=5.25, range 65-91). Adverse driving outcomes included self-reported incidences of (1) being pulled over by the police, (2) receiving a citation, (3) receiving a recommendation to cease or limit driving, (4) crashes, and (5) state-reported crashes. Results found that older drivers with low self-ratings reported more medical conditions, less driving frequency, and had been given more suggestions to stop/limit their driving; there were no other significant differences between low and high self-raters. Logistic regression revealed older drivers were more likely to have a state-reported crash and receive a suggestion to stop or limit driving. Men were more likely to report all adverse driving outcomes except for receiving a suggestion to stop or limit driving. Regarding self-rated driving, older adults with high ratings were 66% less likely (OR=0.34, 95% CI=0.14-0.85) to have received suggestions to limit or stop driving after accounting for demographics, health and driving frequency. Self-ratings were not predictive of other driving outcomes (being pulled over by the police, receiving a citation, self-reported crashes, or state-reported crashes, ps>0.05). Most older drivers (85.14%) rated themselves as either good or excellent drivers regardless of their actual previous citation or crash rates. Self-rated driving is likely not related to actual driving proficiency as indicated by previous crash involvement in older adults

Counter effect of sucrose on ethanol-induced aggregation of protein.

PubMed

Yadav, Jay Kant; Chandani, N; Pande Prajakt, P R; Chauhan, Jyoti Bala

2010-12-01

The present paper is an attempt to study the mechanism of ethanol induced aggregation of chicken egg albumin and to stabilize the protein against ethanol induced aggregation. The protein aggregation was determined by monitoring the light scattering of protein aggregates spectrophotometrically. The protein undergoes certain structural changes in water-ethanol solution and the degree of aggregation was found to be linearly depending upon the concentration of alcohol used. The intrinsic fluorescence study showed a large blue shift in the λ(max) (16 nm) in the presence of 50% ethanol. The ANS fluorescence intensity was found to be gradually increasing with increasing concentration of ethanol. This indicates an increase in the hydrophobic cluster on the protein surface and as a result the hydrophobic interaction is the major driving force for the aggregate formation. Addition of sucrose significantly reduced the ethanol-induced protein aggregation. In presence of 50% sucrose the ethanol the aggregation was reduced to 5%. The study reveals that addition of sucrose brings out changes in the solvent distribution and prevents the structural changes in protein which lead the aggregation.

Protein unfolding with a steric trap.

PubMed

Blois, Tracy M; Hong, Heedeok; Kim, Tae H; Bowie, James U

2009-10-07

The study of protein folding requires a method to drive unfolding, which is typically accomplished by altering solution conditions to favor the denatured state. This has the undesirable consequence that the molecular forces responsible for configuring the polypeptide chain are also changed. It would therefore be useful to develop methods that can drive unfolding without the need for destabilizing solvent conditions. Here we introduce a new method to accomplish this goal, which we call steric trapping. In the steric trap method, the target protein is labeled with two biotin tags placed close in space so that both biotin tags can only be bound by streptavidin when the protein unfolds. Thus, binding of the second streptavidin is energetically coupled to unfolding of the target protein. Testing the method on a model protein, dihydrofolate reductase (DHFR), we find that streptavidin binding can drive unfolding and that the apparent binding affinity reports on changes in DHFR stability. Finally, by employing the slow off-rate of wild-type streptavidin, we find that DHFR can be locked in the unfolded state. The steric trap method provides a simple method for studying aspects of protein folding and stability in native solvent conditions, could be used to specifically unfold selected domains, and could be applicable to membrane proteins.

Dynamic measurement of fluorescent proteins spectral distribution on virus infected cells

NASA Astrophysics Data System (ADS)

Lee, Ja-Yun; Wu, Ming-Xiu; Kao, Chia-Yun; Wu, Tzong-Yuan; Hsu, I.-Jen

2006-09-01

We constructed a dynamic spectroscopy system that can simultaneously measure the intensity and spectral distributions of samples with multi-fluorophores in a single scan. The system was used to monitor the fluorescence distribution of cells infected by the virus, which is constructed by a recombinant baculoviruses, vAcD-Rhir-E, containing the red and green fluorescent protein gene that can simultaneously produce dual fluorescence in recombinant virus-infected Spodoptera frugiperda 21 cells (Sf21) under the control of a polyhedrin promoter. The system was composed of an excitation light source, a scanning system and a spectrometer. We also developed an algorithm and fitting process to analyze the pattern of fluorescence distribution of the dual fluorescence produced in the recombinant virus-infected cells. All the algorithm and calculation are automatically processed in a visualized scanning program and can monitor the specific region of sample by calculating its intensity distribution. The spectral measurement of each pixel was performed at millisecond range and the two dimensional distribution of full spectrum was recorded within several seconds. We have constructed a dynamic spectroscopy system to monitor the process of virus-infection of cells. The distributions of the dual fluorescence were simultaneously measured at micrometer resolution.

Differential distribution of proteins expressed in companion cells in the sieve element-companion cell complex of rice plants.

PubMed

Fukuda, Akari; Fujimaki, Syu; Mori, Tomoko; Suzui, Nobuo; Ishiyama, Keiki; Hayakawa, Toshihiko; Yamaya, Tomoyuki; Fujiwara, Toru; Yoneyama, Tadakatsu; Hayashi, Hiroaki

2005-11-01

Sieve tubes are comprised of sieve elements, enucleated cells that are incapable of RNA and protein synthesis. The proteins in sieve elements are supplied from the neighboring companion cells through plasmodesmata. In rice plants, it was unclear whether or not all proteins produced in companion cells had the same distribution pattern in the sieve element-companion cell complex. In this study, the distribution pattern of four proteins, beta-glucuronidase (GUS), green fluorescent protein (GFP), thioredoxin h (TRXh) and glutathione S-transferase (GST) were analyzed. The foreign proteins GUS and GFP were expressed in transgenic rice plants under the control of the TRXh gene promoter (PTRXh), a companion cell-specific promoter. Analysis of leaf cross-sections of PTRXh-GUS and PTRXh-GFP plants indicated high accumulation of GUS and GFP, respectively, in companion cells rather than in sieve elements. GUS and GFP were also detected in phloem sap collected from leaf sheaths of the transgenic rice plants, suggesting these proteins could enter sieve elements. Relative amounts of GFP and endogenous phloem proteins, TRXh and GST, in phloem sap and total leaf extracts were compared. Compared to TRXh and GST, GFP content was higher in total leaf extracts, but lower in phloem sap, suggesting that GFP accumulated mainly in companion cells rather than in sieve elements. On the other hand, TRXh and GST appeared to accumulate in sieve elements rather than in companion cells. These results indicate the evidence for differential distribution of proteins between sieve elements and companion cells in rice plants.

The drive-wise project: driving simulator training increases real driving performance in healthy older drivers

PubMed Central

Casutt, Gianclaudio; Theill, Nathan; Martin, Mike; Keller, Martin; Jäncke, Lutz

2014-01-01

Background: Age-related cognitive decline is often associated with unsafe driving behavior. We hypothesized that 10 active training sessions in a driving simulator increase cognitive and on-road driving performance. In addition, driving simulator training should outperform cognitive training. Methods: Ninety-one healthy active drivers (62–87 years) were randomly assigned to one of three groups: (1) a driving simulator training group, (2) an attention training group (vigilance and selective attention), or (3) a control group. The main outcome variables were on-road driving and cognitive performance. Seventy-seven participants (85%) completed the training and were included in the analyses. Training gains were analyzed using a multiple regression analysis with planned orthogonal comparisons. Results: The driving simulator-training group showed an improvement in on-road driving performance compared to the attention-training group. In addition, both training groups increased cognitive performance compared to the control group. Conclusion: Driving simulator training offers the potential to enhance driving skills in older drivers. Compared to the attention training, the simulator training seems to be a more powerful program for increasing older drivers' safety on the road. PMID:24860497

DriveWise: an interdisciplinary hospital-based driving assessment program.

PubMed

O'Connor, Margaret G; Kapust, Lissa R; Hollis, Ann M

2008-01-01

Health care professionals working with the elderly have opportunities through research and clinical practice to shape public policy affecting the older driver. This article describes DriveWise, an interdisciplinary hospital-based driving assessment program developed in response to clinical concerns about the driving safety of individuals with medical conditions. DriveWise clinicians use evidence-based, functional assessments to determine driving competence. In addition, the program was designed to meet the emotional needs of individuals whose driving safety has been called into question. To date, approximately 380 participants have been assessed through DriveWise. The following report details the DriveWise mission, DriveWise team members, and road test results. We continue to refine the assessment process to promote safety and support the dignity and independence of all participants. The DriveWise interdisciplinary approach to practice is a concrete example of how gerontological education across professions can have direct benefits to the older adult.

Driving anger in Ukraine: Appraisals, not trait driving anger, predict anger intensity while driving.

PubMed

Stephens, A N; Hill, T; Sullman, M J M

2016-03-01

Trait driving anger is often, but not always, found to predict both the intensity of anger while driving and subsequent crash-related behaviours. However, a number of studies have not found support for a direct relationship between one's tendency to become angry and anger reported while driving, suggesting that other factors may mediate this relationship. The present self-report study investigated whether, in anger provoking driving situations, the appraisals made by drivers influence the relationship between trait and state anger. A sample of 339 drivers from Ukraine completed the 33-item version of the Driver Anger Scale (DAS; Deffenbacher et al., 1994) and eight questions about their most recent experience of driving anger. A structural equation model found that the intensity of anger experienced was predicted by the negative evaluations of the situation, which was in turn predicted by trait driving anger. However, trait driving anger itself did not predict anger intensity; supporting the hypothesis that evaluations of the driving situation mediate the relationship between trait and state anger. Further, the unique structure of the DAS required to fit the data from the Ukrainian sample, may indicate that the anger inducing situations in Ukraine are different to those of a more developed country. Future research is needed to investigate driving anger in Ukraine in a broader sample and also to confirm the role of the appraisal process in the development of driving anger in both developed and undeveloped countries. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cerebral vascular amyloid seeds drive amyloid β-protein fibril assembly with a distinct anti-parallel structure

PubMed Central

Xu, Feng; Fu, Ziao; Dass, Sharmila; Kotarba, AnnMarie E.; Davis, Judianne; Smith, Steven O.; Van Nostrand, William E.

2016-01-01

Cerebrovascular accumulation of amyloid β-protein (Aβ), a condition known as cerebral amyloid angiopathy (CAA), is a common pathological feature of patients with Alzheimer's disease. Familial Aβ mutations, such as Dutch-E22Q and Iowa-D23N, can cause severe cerebrovascular accumulation of amyloid that serves as a potent driver of vascular cognitive impairment and dementia. The distinctive features of vascular amyloid that underlie its unique pathological properties remain unknown. Here, we use transgenic mouse models producing CAA mutants (Tg-SwDI) or overproducing human wild-type Aβ (Tg2576) to demonstrate that CAA-mutant vascular amyloid influences wild-type Aβ deposition in brain. We also show isolated microvascular amyloid seeds from Tg-SwDI mice drive assembly of human wild-type Aβ into distinct anti-parallel β-sheet fibrils. These findings indicate that cerebrovascular amyloid can serve as an effective scaffold to promote rapid assembly and strong deposition of Aβ into a unique structure that likely contributes to its distinctive pathology. PMID:27869115

Tuning CRISPR-Cas9 Gene Drives in Saccharomyces cerevisiae

PubMed Central

Roggenkamp, Emily; Giersch, Rachael M.; Schrock, Madison N.; Turnquist, Emily; Halloran, Megan; Finnigan, Gregory C.

2018-01-01

Control of biological populations is an ongoing challenge in many fields, including agriculture, biodiversity, ecological preservation, pest control, and the spread of disease. In some cases, such as insects that harbor human pathogens (e.g., malaria), elimination or reduction of a small number of species would have a dramatic impact across the globe. Given the recent discovery and development of the CRISPR-Cas9 gene editing technology, a unique arrangement of this system, a nuclease-based “gene drive,” allows for the super-Mendelian spread and forced propagation of a genetic element through a population. Recent studies have demonstrated the ability of a gene drive to rapidly spread within and nearly eliminate insect populations in a laboratory setting. While there are still ongoing technical challenges to design of a more optimal gene drive to be used in wild populations, there are still serious ecological and ethical concerns surrounding the nature of this powerful biological agent. Here, we use budding yeast as a safe and fully contained model system to explore mechanisms that might allow for programmed regulation of gene drive activity. We describe four conserved features of all CRISPR-based drives and demonstrate the ability of each drive component—Cas9 protein level, sgRNA identity, Cas9 nucleocytoplasmic shuttling, and novel Cas9-Cas9 tandem fusions—to modulate drive activity within a population. PMID:29348295

Driving simulation for evaluation and rehabilitation of driving after stroke.

PubMed

Akinwuntan, Abiodun Emmanuel; Wachtel, Jerry; Rosen, Peter Newman

2012-08-01

Driving is an important activity of daily living. Loss of driving privileges can lead to depression, decreased access to medical care, and increased healthcare costs. The ability to drive is often affected after stroke. In approximately 30% of stroke survivors, it is clear from the onset that driving will no longer be possible. Approximately 33% of survivors will be able to return to driving with little or no retraining, and 35% will require driving-related rehabilitation before they can resume safe driving again. The ability to drive is not routinely evaluated after stroke, and there is no established rehabilitation program for poststroke driving. When driving evaluation does occur, it is not always clear which tests are the most salient for accurately assessing poststroke driving ability. Investigators have examined the efficacy of various methodologies to predict driving performance after stroke and have found mixed results, with each method having unique weaknesses, including poor predictive ability, poor face validity, poor sensitivity or specificity, and limited reliability. Here we review common models of driving to gain insight into why single-construct visual or cognitive off-road measures are inadequate for evaluating driving, a complex and dynamic activity that involves timely interaction of multiple motor, visual, cognitive, and perceptual skills. We also examine the potential for driving simulators to overcome the problems currently faced in the evaluation and rehabilitation of driving after stroke. Finally, we offer suggestions for the future direction of simulator-based poststroke driving evaluation and training. Copyright © 2012 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Schmallenberg virus non-structural protein NSm: Intracellular distribution and role of non-hydrophobic domains.

PubMed

Kraatz, Franziska; Wernike, Kerstin; Reiche, Sven; Aebischer, Andrea; Reimann, Ilona; Beer, Martin

2018-03-01

Schmallenberg virus (SBV) induces fetal malformation, abortions and stillbirth in ruminants. While the non-structural protein NSs is a major virulence factor, the biological function of NSm, the second non-structural protein which consists of three hydrophobic transmembrane (I, III, V) and two non-hydrophobic regions (II, IV), is still unknown. Here, a series of NSm mutants displaying deletions of nearly the entire NSm or of the non-hydrophobic domains was generated and the intracellular distribution of NSm was assessed. SBV-NSm is dispensable for the generation of infectious virus and mutants lacking domains II - V showed growth properties similar to the wild-type virus. In addition, a comparable intracellular distribution of SBV-NSm was observed in mammalian cells infected with domain II mutants or wild-type virus. In both cases, NSm co-localized with the glycoprotein Gc in the Golgi compartment. However, domain IV-deletion mutants showed an altered distribution pattern and no co-localization of NSm and Gc. Copyright © 2018 Elsevier Inc. All rights reserved.

Cerebral oscillatory activity during simulated driving using MEG

PubMed Central

Sakihara, Kotoe; Hirata, Masayuki; Ebe, Kazutoshi; Kimura, Kenji; Yi Ryu, Seong; Kono, Yoshiyuki; Muto, Nozomi; Yoshioka, Masako; Yoshimine, Toshiki; Yorifuji, Shiro

2014-01-01

We aimed to examine cerebral oscillatory differences associated with psychological processes during simulated car driving. We recorded neuromagnetic signals in 14 healthy volunteers using magnetoencephalography (MEG) during simulated driving. MEG data were analyzed using synthetic aperture magnetometry to detect the spatial distribution of cerebral oscillations. Group effects between subjects were analyzed statistically using a non-parametric permutation test. Oscillatory differences were calculated by comparison between “passive viewing” and “active driving.” “Passive viewing” was the baseline, and oscillatory differences during “active driving” showed an increase or decrease in comparison with a baseline. Power increase in the theta band was detected in the superior frontal gyrus (SFG) during active driving. Power decreases in the alpha, beta, and low gamma bands were detected in the right inferior parietal lobe (IPL), left postcentral gyrus (PoCG), middle temporal gyrus (MTG), and posterior cingulate gyrus (PCiG) during active driving. Power increase in the theta band in the SFG may play a role in attention. Power decrease in the right IPL may reflect selectively divided attention and visuospatial processing, whereas that in the left PoCG reflects sensorimotor activation related to driving manipulation. Power decreases in the MTG and PCiG may be associated with object recognition. PMID:25566017

Solar wind driving and substorm triggering

NASA Astrophysics Data System (ADS)

Newell, Patrick T.; Liou, Kan

2011-03-01

We compare solar wind driving and its changes for three data sets: (1) 4861 identifications of substorm onsets from satellite global imagers (Polar UVI and IMAGE FUV); (2) a similar number of otherwise random times chosen with a similar solar wind distribution (slightly elevated driving); (3) completely random times. Multiple measures of solar wind driving were used, including interplanetary magnetic field (IMF) Bz, the Kan-Lee electric field, the Borovsky function, and dΦMP/dt (all of which estimate dayside merging). Superposed epoch analysis verifies that the mean Bz has a northward turning (or at least averages less southward) starting 20 min before onset. We argue that the delay between IMF impact on the magnetopause and tail effects appearing in the ionosphere is about that long. The northward turning is not the effect of a few extreme events. The median field shows the same result, as do all other measures of solar wind driving. We compare the rate of northward turning to that observed after random times with slightly elevated driving. The subsequent reversion to mean is essentially the same between random elevations and substorms. To further verify this, we consider in detail the distribution of changes from the statistical peak (20 min prior to onset) to onset. For Bz, the mean change after onset is +0.14 nT (i.e., IMF becomes more northward), but the standard deviation is σ = 2.8 nT. Thus large changes in either direction are common. For EKL, the change is -15 nT km/s ± 830 nT km/s. Thus either a hypothesis predicting northward turnings or one predicting southward turnings would find abundant yet random confirming examples. Indeed, applying the Lyons et al. (1997) trigger criteria (excluding only the prior requirement of 22/30 min Bz < 0, which is often not valid for actual substorms) to these three sets of data shows that "northward turning triggers" occur in 23% of the random data, 24% of the actual substorms, and after 27% of the random elevations

Driving pressure and mechanical power: new targets for VILI prevention.

PubMed

Tonetti, Tommaso; Vasques, Francesco; Rapetti, Francesca; Maiolo, Giorgia; Collino, Francesca; Romitti, Federica; Camporota, Luigi; Cressoni, Massimo; Cadringher, Paolo; Quintel, Michael; Gattinoni, Luciano

2017-07-01

Several factors have been recognized as possible triggers of ventilator-induced lung injury (VILI). The first is pressure (thus the 'barotrauma'), then the volume (hence the 'volutrauma'), finally the cyclic opening-closing of the lung units ('atelectrauma'). Less attention has been paid to the respiratory rate and the flow, although both theoretical considerations and experimental evidence attribute them a significant role in the generation of VILI. The initial injury to the lung parenchyma is necessarily mechanical and it could manifest as an unphysiological distortion of the extracellular matrix and/or as micro-fractures in the hyaluronan, likely the most fragile polymer embedded in the matrix. The order of magnitude of the energy required to break a molecular bond between the hyaluronan and the associated protein is 1.12×10 -16 Joules (J), 70-90% higher than the average energy delivered by a single breath of 1L assuming a lung elastance of 10 cmH 2 O/L (0.5 J). With a normal statistical distribution of the bond strength some polymers will be exposed each cycle to an energy large enough to rupture. Both the extracellular matrix distortion and the polymer fractures lead to inflammatory increase of capillary permeability with edema if a pulmonary blood flow is sufficient. The mediation analysis of higher vs. lower tidal volume and PEEP studies suggests that the driving pressure, more than tidal volume, is the best predictor of VILI, as inferred by increased mortality. This is not surprising, as both tidal volume and respiratory system elastance (resulting in driving pressure) may independently contribute to the mortality. For the same elastance driving pressure is a predictor similar to plateau pressure or tidal volume. Driving pressure is one of the components of the mechanical power, which also includes respiratory rate, flow and PEEP. Finding the threshold for mechanical power would greatly simplify assessment and prevention of VILI.

Mechanical stress and network structure drive protein dynamics during cytokinesis.

PubMed

Srivastava, Vasudha; Robinson, Douglas N

2015-03-02

Cell-shape changes associated with processes like cytokinesis and motility proceed on several-second timescales but are derived from molecular events, including protein-protein interactions, filament assembly, and force generation by molecular motors, all of which occur much faster [1-4]. Therefore, defining the dynamics of such molecular machinery is critical for understanding cell-shape regulation. In addition to signaling pathways, mechanical stresses also direct cytoskeletal protein accumulation [5-7]. A myosin-II-based mechanosensory system controls cellular contractility and shape during cytokinesis and under applied stress [6, 8]. In Dictyostelium, this system tunes myosin II accumulation by feedback through the actin network, particularly through the crosslinker cortexillin I. Cortexillin-binding IQGAPs are major regulators of this system. Here, we defined the short timescale dynamics of key cytoskeletal proteins during cytokinesis and under mechanical stress, using fluorescence recovery after photobleaching and fluorescence correlation spectroscopy, to examine the dynamic interplay between these proteins. Equatorially enriched proteins including cortexillin I, IQGAP2, and myosin II recovered much more slowly than actin and polar crosslinkers. The mobility of equatorial proteins was greatly reduced at the furrow compared to the interphase cortex, suggesting their stabilization during cytokinesis. This mobility shift did not arise from a single biochemical event, but rather from a global inhibition of protein dynamics by mechanical-stress-associated changes in the cytoskeletal structure. Mechanical tuning of contractile protein dynamics provides robustness to the cytoskeletal framework responsible for regulating cell shape and contributes to cytokinesis fidelity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Modeling Simple Driving Tasks with a One-Boundary Diffusion Model

PubMed Central

Ratcliff, Roger; Strayer, David

2014-01-01

A one-boundary diffusion model was applied to the data from two experiments in which subjects were performing a simple simulated driving task. In the first experiment, the same subjects were tested on two driving tasks using a PC-based driving simulator and the psychomotor vigilance test (PVT). The diffusion model fit the response time (RT) distributions for each task and individual subject well. Model parameters were found to correlate across tasks which suggests common component processes were being tapped in the three tasks. The model was also fit to a distracted driving experiment of Cooper and Strayer (2008). Results showed that distraction altered performance by affecting the rate of evidence accumulation (drift rate) and/or increasing the boundary settings. This provides an interpretation of cognitive distraction whereby conversing on a cell phone diverts attention from the normal accumulation of information in the driving environment. PMID:24297620

Distribution of language-related Cntnap2 protein in neural circuits critical for vocal learning.

PubMed

Condro, Michael C; White, Stephanie A

2014-01-01

Variants of the contactin associated protein-like 2 (Cntnap2) gene are risk factors for language-related disorders including autism spectrum disorder, specific language impairment, and stuttering. Songbirds are useful models for study of human speech disorders due to their shared capacity for vocal learning, which relies on similar cortico-basal ganglia circuitry and genetic factors. Here we investigate Cntnap2 protein expression in the brain of the zebra finch, a songbird species in which males, but not females, learn their courtship songs. We hypothesize that Cntnap2 has overlapping functions in vocal learning species, and expect to find protein expression in song-related areas of the zebra finch brain. We further expect that the distribution of this membrane-bound protein may not completely mirror its mRNA distribution due to the distinct subcellular localization of the two molecular species. We find that Cntnap2 protein is enriched in several song control regions relative to surrounding tissues, particularly within the adult male, but not female, robust nucleus of the arcopallium (RA), a cortical song control region analogous to human layer 5 primary motor cortex. The onset of this sexually dimorphic expression coincides with the onset of sensorimotor learning in developing males. Enrichment in male RA appears due to expression in projection neurons within the nucleus, as well as to additional expression in nerve terminals of cortical projections to RA from the lateral magnocellular nucleus of the nidopallium. Cntnap2 protein expression in zebra finch brain supports the hypothesis that this molecule affects neural connectivity critical for vocal learning across taxonomic classes. Copyright © 2013 Wiley Periodicals, Inc.

Impaired Driving

MedlinePlus

... texting Having a medical condition which affects your driving For your safety and the safety of others, do not drive while impaired. Have someone else drive you or take public transportation when you cannot drive. If you need to take a call or send a text ...

A qualitative exploration of driving stress and driving discourtesy.

PubMed

Scott-Parker, B; Jones, C M; Rune, K; Tucker, J

2018-05-31

Driving courtesy, and conversely driving discourtesy, recently has been of great interest in the public domain. In addition, there has been increasing recognition of the negative impact of stress upon the individual's health and wellbeing, with a plethora of interventions aimed at minimising stress more generally. The research literature regarding driving dis/courtesy, in comparison, is scant, with a handful of studies examining the dis/courteous driving behaviour of road users, and the relationship between driving discourtesy and driving stress. To examine courteous and discourteous driving experiences, and to explore the impact of stress associated with such driving experiences. Thirty-eight drivers (20 females) from the Sunshine Coast region volunteered to participate in one of four 1-1.5 h focus groups. Content analysis used the verbatim utterances captured via an Mp3 device. Three themes pertaining to stressful and discourteous interactions were identified. Theme one pertained to the driving context: road infrastructure (eg, roundabouts, roadwork), vehicles (eg, features), location (eg, country vs city, unfamiliar areas), and temporal aspects (eg, holidays). Theme two pertained to other road users: their behaviour (eg, tailgating, merging), and unknown factors (eg, illicit and licit drug use). Theme three pertained to the self as road user: their own behaviours (eg, deliberate intimidation), and their emotions (eg, angry reaction to other drivers, being in control). Driving dis/courtesy and driving stress is a complex phenomenon, suggesting complex intervention efforts are required. Driving discourtesy was reported as being highly stressful, therefore intervention efforts which encourage driving courtesy and which foster emotional capacity to cope with stressful circumstances appear warranted. Copyright © 2018. Published by Elsevier Ltd.

EphrinA5 protein distribution in the developing mouse brain

PubMed Central

2010-01-01

Background EphrinA5 is one of the best-studied members of the Eph-ephrin family of guidance molecules, known to be involved in brain developmental processes. Using in situ hybridization, ephrinA5 mRNA expression has been detected in the retinotectal, the thalamocortical, and the olfactory systems; however, no study focused on the distribution of the protein. Considering that this membrane-anchored molecule may act far from the neuron soma expressing the transcript, it is of a crucial interest to localize ephrinA5 protein to better understand its function. Results Using immunohistochemistry, we found that ephrinA5 protein is highly expressed in the developing mouse brain from E12.5 to E16.5. The olfactory bulb, the cortex, the striatum, the thalamus, and the colliculi showed high intensity of labelling, suggesting its implication in topographic mapping of olfactory, retinocollicular, thalamocortical, corticothalamic and mesostriatal systems. In the olfactory nerve, we found an early ephrinA5 protein expression at E12.5 suggesting its implication in the guidance of primary olfactory neurons into the olfactory bulb. In the thalamus, we detected a dynamic graduated protein expression, suggesting its role in the corticothalamic patterning, whereas ephrinA5 protein expression in the target region of mesencephalic dopaminergic neurones indicated its involvement in the mesostriatal topographic mapping. Following E16.5, the signal faded gradually and was barely detectable at P0, suggesting a main role for ephrinA5 in primary molecular events in topographic map formation. Conclusion Our work shows that ephrinA5 protein is expressed in restrictive regions of the developing mouse brain. This expression pattern points out the potential sites of action of this molecule in the olfactory, retinotectal, thalamocortical, corticothalamic and mesostriatal systems, during development. This study is essential to better understand the role of ephrinA5 during developmental topographic

Distribution of protein motors along the lateral wall of the outer hair cell.

PubMed

Wada, H; Usukura, H; Takeuchi, S; Sugawara, M; Kakehata, S; Ikeda, K

2001-12-01

The outer hair cell (OHC) plays an important role in the normal functioning of the cochlea, and cochlear amplification is believed to be based on OHC electromotility. This electromotility putatively arises from a conformational change of molecules, i.e., 'protein motors', which would be distributed along the plasma membrane. Although it has been assumed that protein motors are distributed in a restricted area of the plasma membrane, details of such distribution remain unclarified. In this study, first, in order to understand the difference in the stiffness along the cell axis, the local deformation of the OHC in response to hypotonic stimulation is analyzed by measuring the displacement of microspheres attached randomly to the lateral wall of the cell. As a result, the stiffness is expected to be constant throughout the region except in the apical part of the cell, and the stiffness of the apical part is expected to be higher than that of the other regions. Then, the local elongation and contraction of the OHC in response to sinusoidal voltage stimulation are analyzed by measuring the displacement of the microspheres in the same way as in the case of the hypotonic stimulation. From the two measurements mentioned above, it is concluded that there are no motors in the apical and basal parts of the cell, and that the motors are equally distributed along the cell lateral wall in the middle part of the cell.

Neurofilament protein is differentially distributed in subpopulations of corticocortical projection neurons in the macaque monkey visual pathways

NASA Technical Reports Server (NTRS)

Hof, P. R.; Ungerleider, L. G.; Webster, M. J.; Gattass, R.; Adams, M. M.; Sailstad, C. A.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)

1996-01-01

Previous studies of the primate cerebral cortex have shown that neurofilament protein is present in pyramidal neuron subpopulations displaying specific regional and laminar distribution patterns. In order to characterize further the neurochemical phenotype of the neurons furnishing feedforward and feedback pathways in the visual cortex of the macaque monkey, we performed an analysis of the distribution of neurofilament protein in corticocortical projection neurons in areas V1, V2, V3, V3A, V4, and MT. Injections of the retrogradely transported dyes Fast Blue and Diamidino Yellow were placed within areas V4 and MT, or in areas V1 and V2, in 14 adult rhesus monkeys, and the brains of these animals were processed for immunohistochemistry with an antibody to nonphosphorylated epitopes of the medium and heavy molecular weight subunits of the neurofilament protein. Overall, there was a higher proportion of neurons projecting from areas V1, V2, V3, and V3A to area MT that were neurofilament protein-immunoreactive (57-100%), than to area V4 (25-36%). In contrast, feedback projections from areas MT, V4, and V3 exhibited a more consistent proportion of neurofilament protein-containing neurons (70-80%), regardless of their target areas (V1 or V2). In addition, the vast majority of feedback neurons projecting to areas V1 and V2 were located in layers V and VI in areas V4 and MT, while they were observed in both supragranular and infragranular layers in area V3. The laminar distribution of feedforward projecting neurons was heterogeneous. In area V1, Meynert and layer IVB cells were found to project to area MT, while neurons projecting to area V4 were particularly dense in layer III within the foveal representation. In area V2, almost all neurons projecting to areas MT or V4 were located in layer III, whereas they were found in both layers II-III and V-VI in areas V3 and V3A. These results suggest that neurofilament protein identifies particular subpopulations of

Drosophila Pelle phosphorylates Dichaete protein and influences its subcellular distribution in developing oocytes.

PubMed

Mutsuddi, Mousumi; Mukherjee, Ashim; Shen, Baohe; Manley, James L; Nambu, John R

2010-01-01

The Drosophila Dichaete gene encodes a member of the Sox family of high mobility group (HMG) domain proteins that have crucial gene regulatory functions in diverse developmental processes. The subcellular localization and transcriptional regulatory activities of Sox proteins can be regulated by several post-translational modifications. To identify genes that functionally interact with Dichaete, we undertook a genetic modifier screen based on a Dichaete gain-of-function phenotype in the adult eye. Mutations in several genes, including decapentaplegic, engrailed and pelle, behaved as dominant modifiers of this eye phenotype. Further analysis of pelle mutants revealed that loss of pelle function results in alterations in the distinctive cytoplasmic distribution of Dichaete protein within the developing oocyte, as well as defects in the elaboration of individual egg chambers. The death domain-containing region of the Pelle protein kinase was found to associate with both Dichaete and mouse Sox2 proteins, and Pelle can phosphorylate Dichaete protein in vitro. Overall, these findings reveal that maternal functions of pelle are essential for proper localization of Dichaete protein in the oocyte and normal egg chamber formation. Dichaete appears to be a novel phosphorylation substrate for Pelle and may function in a Pelle-dependent signaling pathway during oogenesis.

Holokinetic drive: centromere drive in chromosomes without centromeres.

PubMed

Bureš, Petr; Zedek, František

2014-08-01

Similar to how the model of centromere drive explains the size and complexity of centromeres in monocentrics (organisms with localized centromeres), our model of holokinetic drive is consistent with the divergent evolution of chromosomal size and number in holocentrics (organisms with nonlocalized centromeres) exhibiting holokinetic meiosis (holokinetics). Holokinetic drive is proposed to facilitate chromosomal fission and/or repetitive DNA removal (or any segmental deletion) when smaller homologous chromosomes are preferentially inherited or chromosomal fusion and/or repetitive DNA proliferation (or any segmental duplication) when larger homologs are preferred. The hypothesis of holokinetic drive is supported primarily by the negative correlation between chromosome number and genome size that is documented in holokinetic lineages. The supporting value of two older cross-experiments on holokinetic structural heterozygotes (the rush Luzula elegans and butterflies of the genus Antheraea) that indicate the presence of size-preferential homolog transmission via female meiosis for holokinetic drive is discussed, along with the further potential consequences of holokinetic drive in comparison with centromere drive. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

Protein- protein interaction detection system using fluorescent protein microdomains

DOEpatents

Waldo, Geoffrey S.; Cabantous, Stephanie

2010-02-23

The invention provides a protein labeling and interaction detection system based on engineered fragments of fluorescent and chromophoric proteins that require fused interacting polypeptides to drive the association of the fragments, and further are soluble and stable, and do not change the solubility of polypeptides to which they are fused. In one embodiment, a test protein X is fused to a sixteen amino acid fragment of GFP (.beta.-strand 10, amino acids 198-214), engineered to not perturb fusion protein solubility. A second test protein Y is fused to a sixteen amino acid fragment of GFP (.beta.-strand 11, amino acids 215-230), engineered to not perturb fusion protein solubility. When X and Y interact, they bring the GFP strands into proximity, and are detected by complementation with a third GFP fragment consisting of GFP amino acids 1-198 (strands 1-9). When GFP strands 10 and 11 are held together by interaction of protein X and Y, they spontaneous association with GFP strands 1-9, resulting in structural complementation, folding, and concomitant GFP fluorescence.

Driving Anger and Driving Behavior in Adults with ADHD

ERIC Educational Resources Information Center

Richards, Tracy L.; Deffenbacher, Jerry L.; Rosen, Lee A.; Barkley, Russell A.; Rodricks, Trisha

2006-01-01

Objective: This study assesses whether anger in the context of driving is associated with the negative driving outcomes experienced by individuals with ADHD. Method: ADHD adults (n = 56) complete measures of driving anger, driving anger expression, angry thoughts behind the wheel, and aggressive, risky, and crash-related behavior. Results are…

Monitoring protein-protein interactions using split synthetic renilla luciferase protein-fragment-assisted complementation.

PubMed

Paulmurugan, R; Gambhir, S S

2003-04-01

In this study we developed an inducible synthetic renilla luciferase protein-fragment-assisted complementation-based bioluminescence assay to quantitatively measure real time protein-protein interactions in mammalian cells. We identified suitable sites to generate fragments of N and C portions of the protein that yield significant recovered activity through complementation. We validate complementation-based activation of split synthetic renilla luciferase protein driven by the interaction of two strongly interacting proteins, MyoD and Id, in five different cell lines utilizing transient transfection studies. The expression level of the system was also modulated by tumor necrosis factor alpha through NFkappaB-promoter/enhancer elements used to drive expression of the N portion of synthetic renilla luciferase reporter gene. This new system should help in studying protein-protein interactions and when used with other split reporters (e.g., split firefly luciferase) should help to monitor different components of an intracellular network.

TEXTING WHILE DRIVING: EVALUATION OF GLANCE DISTRIBUTIONS FOR FREQUENT/INFREQUENT TEXTERS AND KEYPAD/TOUCHPAD TEXTERS

PubMed Central

Samuel, Siby; Pollatsek, Alexander; Fisher, Donald

2012-01-01

Summary The threat that cell-phones pose to driving has been a well researched topic. There are fewer studies of the threat that texting creates for drivers, but the risks are obvious and the few existing studies confirm this. What is not obvious is whether frequent texters will expose themselves to the same risks as infrequent texters. This is important to know because many texters, especially teens who text frequently, may consider themselves immune to the dangers of texting while driving. As such, a comparison of frequent and infrequent texters was undertaken on a driving simulator. It is also not immediately clear what effects the different types of interfaces have on driving performance while text messaging. The interfaces under evaluation included keypad or “qwerty” phones (e.g., Blackberries) and touchpad phones (iPhone). It was found that the frequent and infrequent texters were equally likely to glance at least once for more than 2s inside the vehicle while sending a text message. It was also found that touchpad texters had a larger number of glances above the 2s threshold than keypad users, though this difference was not significant. The implications of this for future public policy are discussed. PMID:25279388

Cognitive problems, self-rated changes in driving skills, driving-related discomfort and self-regulation of driving in old drivers.

PubMed

Meng, Annette; Siren, Anu

2012-11-01

Ageing in general is associated with functional decline that may have an adverse effect on driving. Nevertheless, older drivers have been found to show good judgement and to self-regulate their driving, which may enable them to continue driving safely despite functional decline. The process of the self-monitoring of driving ability and the awareness of functional decline, and its association with the self-regulation of driving is, however, not fully understood. The aim of the present study was to examine the perceived changes in driving skills, the discomfort experienced in driving, and the self-regulation of driving as measured by the avoidance of certain driving situations by older drivers with different levels of self-rated cognitive problems. Eight hundred and forty Danish drivers aged 75-95 completed a structured telephone interview. The results showed that the recognition of cognitive problems was associated with an experience of improvement in higher level driving skills but also of a decline in lower level driving skills. Moreover, cognitive problems recognised by drivers were associated with discomfort in, and avoidance of, driving situations. Finally, a linear relationship between discomfort in driving and avoidance was found and this tended to be stronger for drivers recognising cognitive problems. The results indicate that older drivers who recognise problems with cognitive functions display good self-assessment of changes in their driving skills. In addition, the results suggest that driving-related discomfort is an important factor affecting the self-regulation of driving. Finally, the findings indicate that driving-related discomfort functions as an indirect self-monitoring of driving ability and may contribute to the safe driving performance of Danish older drivers. Copyright © 2012 Elsevier Ltd. All rights reserved.

Arabinogalactan proteins in root and pollen-tube cells: distribution and functional aspects

PubMed Central

Nguema-Ona, Eric; Coimbra, Sílvia; Vicré-Gibouin, Maïté; Mollet, Jean-Claude; Driouich, Azeddine

2012-01-01

Background Arabinogalactan proteins (AGPs) are complex proteoglycans of the cell wall found in the entire plant kingdom and in almost all plant organs. AGPs encompass a large group of heavily glycosylated cell-wall proteins which share common features, including the presence of glycan chains especially enriched in arabinose and galactose and a protein backbone particularly rich in hydroxyproline residues. However, AGPs also exhibit strong heterogeneities among their members in various plant species. AGP ubiquity in plants suggests these proteoglycans are fundamental players for plant survival and development. Scope In this review, we first present an overview of current knowledge and specific features of AGPs. A section devoted to major tools used to study AGPs is also presented. We then discuss the distribution of AGPs as well as various aspects of their functional properties in root tissues and pollen tubes. This review also suggests novel directions of research on the role of AGPs in the biology of roots and pollen tubes. PMID:22786747

A species-specific nucleosomal signature defines a periodic distribution of amino acids in proteins.

PubMed

Quintales, Luis; Soriano, Ignacio; Vázquez, Enrique; Segurado, Mónica; Antequera, Francisco

2015-04-01

Nucleosomes are the basic structural units of chromatin. Most of the yeast genome is organized in a pattern of positioned nucleosomes that is stably maintained under a wide range of physiological conditions. In this work, we have searched for sequence determinants associated with positioned nucleosomes in four species of fission and budding yeasts. We show that mononucleosomal DNA follows a highly structured base composition pattern, which differs among species despite the high degree of histone conservation. These nucleosomal signatures are present in transcribed and non-transcribed regions across the genome. In the case of open reading frames, they correctly predict the relative distribution of codons on mononucleosomal DNA, and they also determine a periodicity in the average distribution of amino acids along the proteins. These results establish a direct and species-specific connection between the position of each codon around the histone octamer and protein composition.

Antibodies to the core proteins of Nairobi sheep disease virus/Ganjam virus reveal details of the distribution of the proteins in infected cells and tissues.

PubMed

Lasecka, Lidia; Bin-Tarif, Abdelghani; Bridgen, Anne; Juleff, Nicholas; Waters, Ryan A; Baron, Michael D

2015-01-01

Nairobi sheep disease virus (NSDV; also called Ganjam virus in India) is a bunyavirus of the genus Nairovirus. It causes a haemorrhagic gastroenteritis in sheep and goats with mortality up to 90%. The virus is closely related to the human pathogen Crimean-Congo haemorrhagic fever virus (CCHFV). Little is currently known about the biology of NSDV. We have generated specific antibodies against the virus nucleocapsid protein (N) and polymerase (L) and used these to characterise NSDV in infected cells and to study its distribution during infection in a natural host. Due to its large size and the presence of a papain-like protease (the OTU-like domain) it has been suggested that the L protein of nairoviruses undergoes an autoproteolytic cleavage into polymerase and one or more accessory proteins. Specific antibodies which recognise either the N-terminus or the C-terminus of the NSDV L protein showed no evidence of L protein cleavage in NSDV-infected cells. Using the specific anti-N and anti-L antibodies, it was found that these viral proteins do not fully colocalise in infected cells; the N protein accumulated near the Golgi at early stages of infection while the L protein was distributed throughout the cytoplasm, further supporting the multifunctional nature of the L protein. These antibodies also allowed us to gain information about the organs and cell types targeted by the virus in vivo. We could detect NSDV in cryosections prepared from various tissues collected post-mortem from experimentally inoculated animals; the virus was found in the mucosal lining of the small and large intestine, in the lungs, and in mesenteric lymph nodes (MLN), where NSDV appeared to target monocytes and/or macrophages.

Pharmacokinetics of warfarin in rats: role of serum protein binding and tissue distribution

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

Cheung, W.K.

The purpose of this study was to explore the role of serum protein binding and tissue distribution in the non-linear pharmacokinetics of warfarin in rats. The first phase of the research was an attempt to elucidate the causes of intersubject differences in serum protein binding of warfarin in rats. It was found that the distribution of S-warfarin between blood and liver, kidneys, muscle, or fatty tissue was non-linear. Based on the tissue distribution data obtained, a physiologically-based pharmacokinetic model was developed to describe the time course of S-warfarin concentrations in the serum and tissues of rats. The proposed model wasmore » able to display the dose-dependent pharmacokinetics of warfarin in rats. Namely a lower clearance and a smaller apparent volume of distribution with increasing dose, which appear to be due to the presence of capacity-limited, high-affinity binding sites for warfarin in various tissues. To determine if the binding of warfarin to the high-affinity binding sites in the liver of rats is reversible, concentrations of S-warfarin in the liver and serum of rats were monitored for a very long time after an intravenous injection of a 1 mg/kg dose. In another study in rats, non-radioactive warfarin was found to be able to displace tissue-bound C/sup 14/-warfarin which was administered about 200 hours before the i.v. injection of the non-radioactive warfarin, showing that the binding of warfarin to the high-affinity binding sites in the body is persistent and reversible.« less

Population distributions of time to collision at brake application during car following from naturalistic driving data.

PubMed

Kusano, Kristofer D; Chen, Rong; Montgomery, Jade; Gabler, Hampton C

2015-09-01

Forward collision warning (FCW) systems are designed to mitigate the effects of rear-end collisions. Driver acceptance of these systems is crucial to their success, as perceived "nuisance" alarms may cause drivers to disable the systems. In order to make customizable FCW thresholds, system designers need to quantify the variation in braking behavior in the driving population. The objective of this study was to quantify the time to collision (TTC) that drivers applied the brakes during car following scenarios from a large scale naturalistic driving study (NDS). Because of the large amount of data generated by NDS, an automated algorithm was developed to identify lead vehicles using radar data recorded as part of the study. Using the search algorithm, all trips from 64 drivers from the 100-Car NDS were analyzed. A comparison of the algorithm to 7135 brake applications where the presence of a lead vehicle was manually identified found that the algorithm agreed with the human review 90.6% of the time. This study examined 72,123 trips that resulted in 2.6 million brake applications. Population distributions of the minimum, 1st, and 10th percentiles were computed for each driver in speed ranges between 3 and 60 mph in 10 mph increments. As speed increased, so did the minimum TTC experience by drivers as well as variance in TTC. Younger drivers (18-30) had lower TTC at brake application compared to older drivers (30-51+), especially at speeds between 40 mph and 60 mph. This is one of the first studies to use large scale NDS data to quantify braking behavior during car following. The results of this study can be used to design and evaluate FCW systems and calibrate traffic simulation models. Copyright © 2015 Elsevier Ltd and National Safety Council. All rights reserved.

Multivesicular Bodies in Neurons: Distribution, Protein Content, and Trafficking Functions

PubMed Central

VON BARTHELD, CHRISTOPHER S.; ALTICK, AMY L.

2011-01-01

Summary Multivesicular bodies (MVBs) are intracellular endosomal organelles characterized by multiple internal vesicles that are enclosed within a single outer membrane. MVBs were initially regarded as purely prelysosomal structures along the degradative endosomal pathway of internalized proteins. MVBs are now known to be involved in numerous endocytic and trafficking functions, including protein sorting, recycling, transport, storage, and release. This review of neuronal MVBs summarizes their research history, morphology, distribution, accumulation of cargo and constitutive proteins, transport, and theories of functions of MVBs in neurons and glia. Due to their complex morphologies, neurons have expanded trafficking and signaling needs, beyond those of “geometrically simpler” cells, but it is not known whether neuronal MVBs perform additional transport and signaling functions. This review examines the concept of compartment-specific MVB functions in endosomal protein trafficking and signaling within synapses, axons, dendrites and cell bodies. We critically evaluate reports of the accumulation of neuronal MVBs based on evidence of stress-induced MVB formation. Furthermore, we discuss potential functions of neuronal and glial MVBs in development, in dystrophic neuritic syndromes, injury, disease, and aging. MVBs may play a role in Alzheimer’s, Huntington’s, and Niemann-Pick diseases, some types of frontotemporal dementia, prion and virus trafficking, as well as in adaptive responses of neurons to trauma and toxin or drug exposure. Functions of MVBs in neurons have been much neglected, and major gaps in knowledge currently exist. Developing truly MVB-specific markers would help to elucidate the roles of neuronal MVBs in intra- and intercellular signaling of normal and diseased neurons. PMID:21216273

Daytime Sleepiness and Driving Performance in Patients with Obstructive Sleep Apnea: Comparison of the MSLT, the MWT, and a Simulated Driving Task

PubMed Central

Pizza, Fabio; Contardi, Sara; Mondini, Susanna; Trentin, Lino; Cirignotta, Fabio

2009-01-01

Study Objectives: To test the reliability of a driving-simulation test for the objective measurement of daytime alertness compared with the Multiple Sleep Latency Test (MSLT) and with the Maintenance of Wakefulness Test (MWT), and to test the ability to drive safely, in comparison with on-road history, in the clinical setting of untreated severe obstructive sleep apnea. Design: N/A. Setting: Sleep laboratory. Patients or Participants: Twenty-four patients with severe obstructive sleep apnea and reported daytime sleepiness varying in severity (as measured by the Epworth Sleepiness Scale). Interventions: N/A. Measurements and Results: Patients underwent MSLT and MWT coupled with 4 sessions of driving-simulation test on 2 different days randomly distributed 1 week apart. Simulated-driving performance (in terms of lane-position variability and crash occurrence) was correlated with sleep latency on the MSLT and more significantly on the MWT, showing a predictive validity toward the detection of sleepy versus alert patients with obstructive sleep apnea. In addition, patients reporting excessive daytime sleepiness or a history of car crashes showed poorer performances on the driving simulator. Conclusions: A simulated driving test is a suitable tool for objective measurement of daytime alertness in patients with obstructive sleep apnea. Further studies are needed to clarify the association between simulated-driving performance and on-road crash risk of patients with sleep disordered breathing. Citation: Pizza F; Contardi S; Mondini S; Trentin L; Cirignotta F. Daytime sleepiness and driving performance in patients with obstructive sleep apnea: comparison of the MSLT, the MWT, and a simulated driving task. SLEEP 2009;32(3):382-391. PMID:19294958

Fast-Response electric drives of Mechanical Engineering objects

NASA Astrophysics Data System (ADS)

Doykina, L. A.; Bukhanov, S. S.; Gryzlov, A. A.

2018-03-01

The article gives a solution to the problem of increasing the speed in the electrical drives of machine-building enterprises due to the application of a structure with ISC control. In this case, it is possible to get rid of the speed sensors. It is noted that in this case no circulating pulsations are applied to the input of the control system, caused by a non-identical interface between the sensor and the shaft of the operating mechanism. For detailed modeling, a mathematical model of an electric drive with distributed parameters was proposed. The calculation of such system was carried out by the finite element method. Taking into account the distributed characteristic of the system parameters allowed one to take into account the discrete nature of the electric machine’s work. The simulation results showed that the response time in the control circuit is estimated at a time constant of 0.0015, which is about twice as fast as in traditional vector control schemes.

Raytracing and Direct-Drive Targets

NASA Astrophysics Data System (ADS)

Schmitt, Andrew J.; Bates, Jason; Fyfe, David; Eimerl, David

2013-10-01

Accurate simulation of the effects of laser imprinting and drive asymmetries in directly driven targets requires the ability to distinguish between raytrace noise and the intensity structure produced by the spatial and temporal incoherence of optical smoothing. We have developed and implemented a smoother raytrace algorithm for our mpi-parallel radiation hydrodynamics code, FAST3D. The underlying approach is to connect the rays into either sheets (in 2D) or volume-enclosing chunks (in 3D) so that the absorbed energy distribution continuously covers the propagation area illuminated by the laser. We will describe the status and show the different scalings encountered in 2D and 3D problems as the computational size, parallelization strategy, and number of rays is varied. Finally, we show results using the method in current NIKE experimental target simulations and in proposed symmetric and polar direct-drive target designs. Supported by US DoE/NNSA.

cOSPREY: A Cloud-Based Distributed Algorithm for Large-Scale Computational Protein Design

PubMed Central

Pan, Yuchao; Dong, Yuxi; Zhou, Jingtian; Hallen, Mark; Donald, Bruce R.; Xu, Wei

2016-01-01

Abstract Finding the global minimum energy conformation (GMEC) of a huge combinatorial search space is the key challenge in computational protein design (CPD) problems. Traditional algorithms lack a scalable and efficient distributed design scheme, preventing researchers from taking full advantage of current cloud infrastructures. We design cloud OSPREY (cOSPREY), an extension to a widely used protein design software OSPREY, to allow the original design framework to scale to the commercial cloud infrastructures. We propose several novel designs to integrate both algorithm and system optimizations, such as GMEC-specific pruning, state search partitioning, asynchronous algorithm state sharing, and fault tolerance. We evaluate cOSPREY on three different cloud platforms using different technologies and show that it can solve a number of large-scale protein design problems that have not been possible with previous approaches. PMID:27154509

Brain activity during driving with distraction: an immersive fMRI study

PubMed Central

Schweizer, Tom A.; Kan, Karen; Hung, Yuwen; Tam, Fred; Naglie, Gary; Graham, Simon J.

2013-01-01

Introduction: Non-invasive measurements of brain activity have an important role to play in understanding driving ability. The current study aimed to identify the neural underpinnings of human driving behavior by visualizing the areas of the brain involved in driving under different levels of demand, such as driving while distracted or making left turns at busy intersections. Materials and Methods: To capture brain activity during driving, we placed a driving simulator with a fully functional steering wheel and pedals in a 3.0 Tesla functional magnetic resonance imaging (fMRI) system. To identify the brain areas involved while performing different real-world driving maneuvers, participants completed tasks ranging from simple (right turns) to more complex (left turns at busy intersections). To assess the effects of driving while distracted, participants were asked to perform an auditory task while driving analogous to speaking on a hands-free device and driving. Results: A widely distributed brain network was identified, especially when making left turns at busy intersections compared to more simple driving tasks. During distracted driving, brain activation shifted dramatically from the posterior, visual and spatial areas to the prefrontal cortex. Conclusions: Our findings suggest that the distracted brain sacrificed areas in the posterior brain important for visual attention and alertness to recruit enough brain resources to perform a secondary, cognitive task. The present findings offer important new insights into the scientific understanding of the neuro-cognitive mechanisms of driving behavior and lay down an important foundation for future clinical research. PMID:23450757

Spatial Distribution of Cellular Function: The Partitioning of Proteins between Mitochondria and the Nucleus in MCF7 Breast Cancer Cells

PubMed Central

Qattan, Amal T.; Radulovic, Marko; Crawford, Mark; Godovac-Zimmermann, Jasminka

2014-01-01

Concurrent proteomics analysis of the nuclei and mitochondria of MCF7 breast cancer cells identified 985 proteins (40% of all detected proteins) present in both organelles. Numerous proteins from all five complexes involved in oxidative phosphorylation (e.g., NDUFA5, NDUFB10, NDUFS1, NDUF2, SDHA, UQRB, UQRC2, UQCRH, COX5A, COX5B, MT-CO2, ATP5A1, ATP5B, ATP5H, etc.), from the TCA-cycle (DLST, IDH2, IDH3A, OGDH, SUCLAG2, etc.), and from glycolysis (ALDOA, ENO1, FBP1, GPI, PGK1, TALDO1, etc.) were distributed to both the nucleus and mitochondria. In contrast, proteins involved in nuclear/mitochondrial RNA processing/translation and Ras/Rab signaling showed different partitioning patterns. The identity of the OxPhos, TCA-cycle, and glycolysis proteins distributed to both the nucleus and mitochondria provides evidence for spatio-functional integration of these processes over the two different subcellular organelles. We suggest that there are unrecognized aspects of functional coordination between the nucleus and mitochondria, that integration of core functional processes via wide subcellular distribution of constituent proteins is a common characteristic of cells, and that subcellular spatial integration of function may be a vital aspect of cancer. PMID:23051583

Unraveling sterol-dependent membrane phenotypes by analysis of protein abundance-ratio distributions in different membrane fractions under biochemical and endogenous sterol depletion.

PubMed

Zauber, Henrik; Szymanski, Witold; Schulze, Waltraud X

2013-12-01

During the last decade, research on plasma membrane focused increasingly on the analysis of so-called microdomains. It has been shown that function of many membrane-associated proteins involved in signaling and transport depends on their conditional segregation within sterol-enriched membrane domains. High throughput proteomic analysis of sterol-protein interactions are often based on analyzing detergent resistant membrane fraction enriched in sterols and associated proteins, which also contain proteins from these microdomain structures. Most studies so far focused exclusively on the characterization of detergent resistant membrane protein composition and abundances. This approach has received some criticism because of its unspecificity and many co-purifying proteins. In this study, by a label-free quantitation approach, we extended the characterization of membrane microdomains by particularly studying distributions of each protein between detergent resistant membrane and detergent-soluble fractions (DSF). This approach allows a more stringent definition of dynamic processes between different membrane phases and provides a means of identification of co-purifying proteins. We developed a random sampling algorithm, called Unicorn, allowing for robust statistical testing of alterations in the protein distribution ratios of the two different fractions. Unicorn was validated on proteomic data from methyl-β-cyclodextrin treated plasma membranes and the sterol biosynthesis mutant smt1. Both, chemical treatment and sterol-biosynthesis mutation affected similar protein classes in their membrane phase distribution and particularly proteins with signaling and transport functions.

Direct activation of Shroom3 transcription by Pitx proteins drives epithelial morphogenesis in the developing gut

PubMed Central

Chung, Mei-I; Nascone-Yoder, Nanette M.; Grover, Stephanie A.; Drysdale, Thomas A.; Wallingford, John B.

2010-01-01

Individual cell shape changes are essential for epithelial morphogenesis. A transcriptional network for epithelial cell shape change is emerging in Drosophila, but this area remains largely unexplored in vertebrates. The distinction is important as so far, key downstream effectors of cell shape change in Drosophila appear not to be conserved. Rather, Shroom3 has emerged as a central effector of epithelial morphogenesis in vertebrates, driving both actin- and microtubule-based cell shape changes. To date, the morphogenetic role of Shroom3 has been explored only in the neural epithelium, so the broad expression of this gene raises two important questions: what are the requirements for Shroom3 in non-neural tissues and what factors control Shroom3 transcription? Here, we show in Xenopus that Shroom3 is essential for cell shape changes and morphogenesis in the developing vertebrate gut and that Shroom3 transcription in the gut requires the Pitx1 transcription factor. Moreover, we show that Pitx proteins directly activate Shroom3 transcription, and we identify Pitx-responsive regulatory elements in the genomic DNA upstream of Shroom3. Finally, we show that ectopic expression of Pitx proteins is sufficient to induce Shroom3-dependent cytoskeletal reorganization and epithelial cell shape change. These data demonstrate new breadth to the requirements for Shroom3 in morphogenesis, and they also provide a cell-biological basis for the role of Pitx transcription factors in morphogenesis. More generally, these results provide a foundation for deciphering the transcriptional network that underlies epithelial cell shape change in developing vertebrates. PMID:20332151

Conceptions of Early Childhood Leadership: Driving New Professionalism?

ERIC Educational Resources Information Center

Sims, Margaret; Forrest, Rhonda; Semann, Anthony; Slattery, Colin

2015-01-01

This study reports the understandings of leadership held by 351 Victorian early childhood leaders (ECLs). Internationally, ECLs are expected to drive quality improvement through mentoring and modelling: a concept associated with distributive leadership. However, ECLs often move into leadership positions by accident and are ill-prepared for their…

Prediction of Carbohydrate Binding Sites on Protein Surfaces with 3-Dimensional Probability Density Distributions of Interacting Atoms

PubMed Central

Tsai, Keng-Chang; Jian, Jhih-Wei; Yang, Ei-Wen; Hsu, Po-Chiang; Peng, Hung-Pin; Chen, Ching-Tai; Chen, Jun-Bo; Chang, Jeng-Yih; Hsu, Wen-Lian; Yang, An-Suei

2012-01-01

Non-covalent protein-carbohydrate interactions mediate molecular targeting in many biological processes. Prediction of non-covalent carbohydrate binding sites on protein surfaces not only provides insights into the functions of the query proteins; information on key carbohydrate-binding residues could suggest site-directed mutagenesis experiments, design therapeutics targeting carbohydrate-binding proteins, and provide guidance in engineering protein-carbohydrate interactions. In this work, we show that non-covalent carbohydrate binding sites on protein surfaces can be predicted with relatively high accuracy when the query protein structures are known. The prediction capabilities were based on a novel encoding scheme of the three-dimensional probability density maps describing the distributions of 36 non-covalent interacting atom types around protein surfaces. One machine learning model was trained for each of the 30 protein atom types. The machine learning algorithms predicted tentative carbohydrate binding sites on query proteins by recognizing the characteristic interacting atom distribution patterns specific for carbohydrate binding sites from known protein structures. The prediction results for all protein atom types were integrated into surface patches as tentative carbohydrate binding sites based on normalized prediction confidence level. The prediction capabilities of the predictors were benchmarked by a 10-fold cross validation on 497 non-redundant proteins with known carbohydrate binding sites. The predictors were further tested on an independent test set with 108 proteins. The residue-based Matthews correlation coefficient (MCC) for the independent test was 0.45, with prediction precision and sensitivity (or recall) of 0.45 and 0.49 respectively. In addition, 111 unbound carbohydrate-binding protein structures for which the structures were determined in the absence of the carbohydrate ligands were predicted with the trained predictors. The overall

Antibodies to the Core Proteins of Nairobi Sheep Disease Virus/Ganjam Virus Reveal Details of the Distribution of the Proteins in Infected Cells and Tissues

PubMed Central

Lasecka, Lidia; Bin-Tarif, Abdelghani; Bridgen, Anne; Juleff, Nicholas; Waters, Ryan A.; Baron, Michael D.

2015-01-01

Nairobi sheep disease virus (NSDV; also called Ganjam virus in India) is a bunyavirus of the genus Nairovirus. It causes a haemorrhagic gastroenteritis in sheep and goats with mortality up to 90%. The virus is closely related to the human pathogen Crimean-Congo haemorrhagic fever virus (CCHFV). Little is currently known about the biology of NSDV. We have generated specific antibodies against the virus nucleocapsid protein (N) and polymerase (L) and used these to characterise NSDV in infected cells and to study its distribution during infection in a natural host. Due to its large size and the presence of a papain-like protease (the OTU-like domain) it has been suggested that the L protein of nairoviruses undergoes an autoproteolytic cleavage into polymerase and one or more accessory proteins. Specific antibodies which recognise either the N-terminus or the C-terminus of the NSDV L protein showed no evidence of L protein cleavage in NSDV-infected cells. Using the specific anti-N and anti-L antibodies, it was found that these viral proteins do not fully colocalise in infected cells; the N protein accumulated near the Golgi at early stages of infection while the L protein was distributed throughout the cytoplasm, further supporting the multifunctional nature of the L protein. These antibodies also allowed us to gain information about the organs and cell types targeted by the virus in vivo. We could detect NSDV in cryosections prepared from various tissues collected post-mortem from experimentally inoculated animals; the virus was found in the mucosal lining of the small and large intestine, in the lungs, and in mesenteric lymph nodes (MLN), where NSDV appeared to target monocytes and/or macrophages. PMID:25905707

The application of quasi-steady approximation in atomic kinetics in simulation of hohlraum radiation drive

NASA Astrophysics Data System (ADS)

Ren, Guoli; Pei, Wenbing; Lan, Ke; Gu, Peijun; Li, Xin; Institute of Applied Physics; Computional Mathematics Team

2011-10-01

In current routine 2D simulation of hohlraum physics, we adopt the principal-quantum- number(n-level) average atom model(AAM). However, the experimental frequency-dependant radiative drive differs from our n-level simulated drive, which reminds us the need of a more detailed atomic kinetics description. The orbital-quantum-number(nl-level) AAM is a natural consideration but the in-line calculation consumes much more resources. We use a new method to built up a nl-level bound electron distribution using in-line n-level calculated plasma condition (such as temperature, density, average ionization degree). We name this method ``quasi-steady approximation.'' Using the re-built nl-level bound electron distribution (Pnl) , we acquire a new hohlraum radiative drive by post-processing. Comparison with the n-level post-processed hohlraum drive shows that we get an almost identical radiation flux but with more-detailed frequency-dependant structures.

Drill drive mechanism

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

Dressel, M.O.

1979-10-30

A drill drive mechanism is especially adapted to provide both rotational drive and axial feed for a drill of substantial diameter such as may be used for drilling holes for roof bolts in mine shafts. The drill shaft is made with a helical pattern of scroll-like projections on its surface for removal of cuttings. The drill drive mechanism includes a plurality of sprockets carrying two chains of drive links which are arranged to interlock around the drill shaft with each drive link having depressions which mate with the scroll-like projections. As the chain links move upwardly or downwardly the surfacesmore » of the depressions in the links mate with the scroll projections to move the shaft axially. Tangs on the drive links mate with notch surfaces between scroll projections to provide a means for rotating the shaft. Projections on the drive links mate together at the center to hold the drive links tightly around the drill shaft. The entire chain drive mechanism is rotated around the drill shaft axis by means of a hydraulic motor and gear drive to cause rotation of the drill shaft. This gear drive also connects with a differential gearset which is interconnected with a second gear. A second motor is connected to the spider shaft of the different gearset to produce differential movement (speeds) at the output gears of the differential gearset. This differential in speed is utilized to drive said second gear at a speed different from the speed of said gear drive, this speed differential being utilized to drive said sprockets for axial movement of said drill shaft. 11 claims.« less

Drill drive mechanism

DOEpatents

Dressel, Michael O.

1979-01-01

A drill drive mechanism is especially adapted to provide both rotational drive and axial feed for a drill of substantial diameter such as may be used for drilling holes for roof bolts in mine shafts. The drill shaft is made with a helical pattern of scroll-like projections on its surface for removal of cuttings. The drill drive mechanism includes a plurality of sprockets carrying two chains of drive links which are arranged to interlock around the drill shaft with each drive link having depressions which mate with the scroll-like projections. As the chain links move upwardly or downwardly the surfaces of the depressions in the links mate with the scroll projections to move the shaft axially. Tangs on the drive links mate with notch surfaces between scroll projections to provide a means for rotating the shaft. Projections on the drive links mate together at the center to hold the drive links tightly around the drill shaft. The entire chain drive mechanism is rotated around the drill shaft axis by means of a hydraulic motor and gear drive to cause rotation of the drill shaft. This gear drive also connects with a differential gearset which is interconnected with a second gear. A second motor is connected to the spider shaft of the differential gearset to produce differential movement (speeds) at the output gears of the differential gearset. This differential in speed is utilized to drive said second gear at a speed different from the speed of said gear drive, this speed differential being utilized to drive said sprockets for axial movement of said drill shaft.

Dimensions of driving anger and their relationships with aberrant driving.

PubMed

Zhang, Tingru; Chan, Alan H S; Zhang, Wei

2015-08-01

The purpose of this study was to investigate the relationship between driving anger and aberrant driving behaviours. An internet-based questionnaire survey was administered to a sample of Chinese drivers, with driving anger measured by a 14-item short Driving Anger Scale (DAS) and the aberrant driving behaviours measured by a 23-item Driver Behaviour Questionnaire (DBQ). The results of Confirmatory Factor Analysis demonstrated that the three-factor model (hostile gesture, arrival-blocking and safety-blocking) of the DAS fitted the driving anger data well. The Exploratory Factor Analysis on DBQ data differentiated four types of aberrant driving, viz. emotional violation, error, deliberate violation and maintaining progress violation. For the anger-aberration relation, it was found that only "arrival-blocking" anger was a significant positive predictor for all four types of aberrant driving behaviours. The "safety-blocking" anger revealed a negative impact on deliberate violations, a finding different from previously established positive anger-aberration relation. These results suggest that drivers with different patterns of driving anger would show different behavioural tendencies and as a result intervention strategies may be differentially effective for drivers of different profiles. Copyright © 2015 Elsevier Ltd. All rights reserved.

A rate distortion approach to protein symmetry.

PubMed

Wallace, Rodrick

2010-08-01

A spontaneous symmetry breaking argument is applied to the problem of protein folding, via a rate distortion analysis of the relation between genome coding and the final condensation of the protein molten globule that is, in spirit, analogous to Tlusty's (2007) exploration of the evolution of the genetic code. In the 'energy' picture, the average distortion between codon message and final protein structure, under constraints driven by evolutionary selection, serves as a temperature analog, so that low values limit the possible distribution of protein forms, producing the canonical folding funnel. A dual 'developmental' perspective sees the rate distortion function itself as the temperature analog, and permits incorporation of chaperons or toxic exposures as catalysts, driving the system to different possible outcomes or affecting the rate of convergence. The rate distortion function appears constrained by the availability of metabolic free energy, with implications for prebiotic evolution, and a nonequilibrium empirical Onsager treatment provides an adaptable statistical model that can be fitted to data, in the same manner as a regression equation. In sum, mechanistic models of protein folding fail to account for the observed spectrum of protein folding and aggregation disorders, suggesting that a biologically based cognitive paradigm describing folding will be needed for understanding the etiology, prevention, and treatment of these diseases. The developmental formalism introduced here may contribute substantially to such a paradigm.

Within-day protein distribution does not influence body composition responses during weight loss in resistance-training adults who are overweight.

PubMed

Hudson, Joshua L; Kim, Jung Eun; Paddon-Jones, Douglas; Campbell, Wayne W

2017-11-01

Background: Emerging research suggests that redistributing total protein intake from 1 high-protein meal/d to multiple moderately high-protein meals improves 24-h muscle protein synthesis. Over time, this may promote positive changes in body composition. Objective: We sought to assess the effects of within-day protein intake distribution on changes in body composition during dietary energy restriction and resistance training. Design: In a randomized parallel-design study, 41 men and women [mean ± SEM age: 35 ± 2 y; body mass index (in kg/m 2 ): 31.5 ± 0.5] consumed an energy-restricted diet (750 kcal/d below the requirement) for 16 wk while performing resistance training 3 d/wk. Subjects consumed 90 g protein/d (1.0 ± 0.03 g · kg -1 · d -1 , 125% of the Recommended Dietary Allowance, at intervention week 1) in either a skewed (10 g at breakfast, 20 g at lunch, and 60 g at dinner; n = 20) or even (30 g each at breakfast, lunch, and dinner; n = 21) distribution pattern. Body composition was measured pre- and postintervention. Results: Over time, whole-body mass (least-squares mean ± SE: -7.9 ± 0.6 kg), whole-body lean mass (-1.0 ± 0.2 kg), whole-body fat mass (-6.9 ± 0.5 kg), appendicular lean mass (-0.7 ± 0.1 kg), and appendicular fat mass (-2.6 ± 0.2 kg) each decreased. The midthigh muscle area (0 ± 1 cm 2 ) did not change over time, whereas the midcalf muscle area decreased (-3 ± 1 cm 2 ). Within-day protein distribution did not differentially affect these body-composition responses. Conclusion: The effectiveness of dietary energy restriction combined with resistance training to improve body composition is not influenced by the within-day distribution of protein when adequate total protein is consumed. This trial was registered at clinicaltrials.gov as NCT02066948. © 2017 American Society for Nutrition.

High reliability linear drive device for artificial hearts

NASA Astrophysics Data System (ADS)

Ji, Jinghua; Zhao, Wenxiang; Liu, Guohai; Shen, Yue; Wang, Fangqun

2012-04-01

In this paper, a new high reliability linear drive device, termed as stator-permanent-magnet tubular oscillating actuator (SPM-TOA), is proposed for artificial hearts (AHs). The key is to incorporate the concept of two independent phases into this linear AH device, hence achieving high reliability operation. The fault-tolerant teeth are employed to provide the desired decoupling phases in magnetic circuit. Also, as the magnets and the coils are located in the stator, the proposed SPM-TOA takes the definite advantages of robust mover and direct-drive capability. By using the time-stepping finite element method, the electromagnetic characteristics of the proposed SPM-TOA are analyzed, including magnetic field distributions, flux linkages, back- electromotive forces (back-EMFs) self- and mutual inductances, as well as cogging and thrust forces. The results confirm that the proposed SPM-TOA meets the dimension, weight, and force requirements of the AH drive device.

Activation of protein kinase C alters the intracellular distribution and mobility of cardiac Na+ channels.

PubMed

Hallaq, Haifa; Wang, Dao W; Kunic, Jennifer D; George, Alfred L; Wells, K Sam; Murray, Katherine T

2012-02-01

Na(+) current derived from expression of the cardiac isoform SCN5A is reduced by receptor-mediated or direct activation of protein kinase C (PKC). Previous work has suggested a possible role for loss of Na(+) channels at the plasma membrane in this effect, but the results are controversial. In this study, we tested the hypothesis that PKC activation acutely modulates the intracellular distribution of SCN5A channels and that this effect can be visualized in living cells. In human embryonic kidney cells that stably expressed SCN5A with green fluorescent protein (GFP) fused to the channel COOH-terminus (SCN5A-GFP), Na(+) currents were suppressed by an exposure to PKC activation. Using confocal microscopy, colocalization of SCN5A-GFP channels with the plasma membrane under control and stimulated conditions was quantified. A separate population of SCN5A channels containing an extracellular epitope was immunolabeled to permit temporally stable labeling of the plasma membrane. Our results demonstrated that Na(+) channels were preferentially trafficked away from the plasma membrane by PKC activation, with a major contribution by Ca(2+)-sensitive or conventional PKC isoforms, whereas stimulation of protein kinase A (PKA) had the opposite effect. Removal of the conserved PKC site Ser(1503) or exposure to the NADPH oxidase inhibitor apocynin eliminated the PKC-mediated effect to alter channel trafficking, indicating that both channel phosphorylation and ROS were required. Experiments using fluorescence recovery after photobleaching demonstrated that both PKC and PKA also modified channel mobility in a manner consistent with the dynamics of channel distribution. These results demonstrate that the activation of protein kinases can acutely regulate the intracellular distribution and molecular mobility of cardiac Na(+) channels in living cells.

The microtubule motor protein KIF13A is involved in intracellular trafficking of the Lassa virus matrix protein Z.

PubMed

Fehling, Sarah Katharina; Noda, Takeshi; Maisner, Andrea; Lamp, Boris; Conzelmann, Karl-Klaus; Kawaoka, Yoshihiro; Klenk, Hans-Dieter; Garten, Wolfgang; Strecker, Thomas

2013-02-01

The small matrix protein Z of arenaviruses has been identified as the main driving force to promote viral particle production at the plasma membrane. Although multiple functions of Z in the arenaviral life cycle have been uncovered, the mechanism of intracellular transport of Z to the site of virus budding is poorly understood and cellular motor proteins that mediate Z trafficking remain to be identified. In the present study, we report that the Z protein of the Old World arenavirus Lassa virus (LASV) interacts with the kinesin family member 13A (KIF13A), a plus-end-directed microtubule-dependent motor protein. Plasmid-driven overexpression of KIF13A results in relocalization of Z to the cell periphery, while functional blockage of endogenous KIF13A by overexpression of a dominant-negative mutant or KIF13A-specific siRNA causes a perinuclearaccumulation and decreased production of both Z-induced virus-like particles and infectious LASV. The interaction of KIF13A with Z proteins from both Old and New World arenaviruses suggests a conserved intracellular transport mechanism. In contrast, the intracellular distribution of the matrix proteins of prototypic members of the paramyxo- and rhabdovirus family is independent of KIF13A. In summary, our studies identify for the first time a molecular motor protein as a critical mediator for intracellular microtubule-dependent transport of arenavirus matrix proteins. © 2012 Blackwell Publishing Ltd.

Membrane shape modulates transmembrane protein distribution.

PubMed

Aimon, Sophie; Callan-Jones, Andrew; Berthaud, Alice; Pinot, Mathieu; Toombes, Gilman E S; Bassereau, Patricia

2014-01-27

Although membrane shape varies greatly throughout the cell, the contribution of membrane curvature to transmembrane protein targeting is unknown because of the numerous sorting mechanisms that take place concurrently in cells. To isolate the effect of membrane shape, we used cell-sized giant unilamellar vesicles (GUVs) containing either the potassium channel KvAP or the water channel AQP0 to form membrane nanotubes with controlled radii. Whereas the AQP0 concentrations in flat and curved membranes were indistinguishable, KvAP was enriched in the tubes, with greater enrichment in more highly curved membranes. Fluorescence recovery after photobleaching measurements showed that both proteins could freely diffuse through the neck between the tube and GUV, and the effect of each protein on membrane shape and stiffness was characterized using a thermodynamic sorting model. This study establishes the importance of membrane shape for targeting transmembrane proteins and provides a method for determining the effective shape and flexibility of membrane proteins. Copyright © 2014 Elsevier Inc. All rights reserved.

Effects of kernel vitreousness and protein level on protein molecular weight distribution, milling quality, and breadmaking quality in hard red spring wheat

USDA-ARS?s Scientific Manuscript database

Dark, hard, and vitreous kernel content is an important grading characteristic for hard red spring (HRS) wheat in the U.S. This research aimed to determine the associations of kernel vitreousness (KV) with protein molecular weight distribution (MWD) and quality traits that were not biased by quanti...

Characterisation of the protein corona using tunable resistive pulse sensing: determining the change and distribution of a particle's surface charge.

PubMed

Blundell, Emma L C J; Healey, Matthew J; Holton, Elizabeth; Sivakumaran, Muttuswamy; Manstana, Sarabjit; Platt, Mark

2016-08-01

The zeta potential of the protein corona around carboxyl particles has been measured using tunable resistive pulse sensing (TRPS). A simple and rapid assay for characterising zeta potentials within buffer, serum and plasma is presented monitoring the change, magnitude and distribution of proteins on the particle surface. First, we measure the change in zeta potential of carboxyl-functionalised nanoparticles in solutions that contain biologically relevant concentrations of individual proteins, typically constituted in plasma and serum, and observe a significant difference in distributions and zeta values between room temperature and 37 °C assays. The effect is protein dependent, and the largest difference between the two temperatures is recorded for the γ-globulin protein where the mean zeta potential changes from -16.7 to -9.0 mV for 25 and 37 °C, respectively. This method is further applied to monitor particles placed into serum and/or plasma. A temperature-dependent change is again observed with serum showing a 4.9 mV difference in zeta potential between samples incubated at 25 and 37 °C; this shift was larger than that observed for samples in plasma (0.4 mV). Finally, we monitor the kinetics of the corona reorientation for particles initially placed into serum and then adding 5 % (V/V) plasma. The technology presented offers an interesting insight into protein corona structure and kinetics of formation measured in biologically relevant solutions, i.e. high protein, high salt levels, and its particle-by-particle analysis gives a measure of the distribution of particle zeta potential that may offer a better understanding of the behaviour of nanoparticles in solution. Graphical Abstract The relative velocity of a nanoparticle as it traverses a nanopore can be used to determine its zeta potential. Monitoring the changes in translocation speeds can therefore be used to follow changes to the surface chemistry/composition of 210 nm particles that were placed

Useful field of view in simulated driving: Reaction times and eye movements of drivers

PubMed Central

Seya, Yasuhiro; Nakayasu, Hidetoshi; Yagi, Tadasu

2013-01-01

To examine the spatial distribution of a useful field of view (UFOV) in driving, reaction times (RTs) and eye movements were measured in simulated driving. In the experiment, a normal or mirror-reversed letter “E” was presented on driving images with different eccentricities and directions from the current gaze position. The results showed significantly slower RTs in the upper and upper left directions than in the other directions. The RTs were significantly slower in the left directions than in the right directions. These results suggest that the UFOV in driving may be asymmetrical among the meridians in the visual field. PMID:24349688

Unraveling Sterol-dependent Membrane Phenotypes by Analysis of Protein Abundance-ratio Distributions in Different Membrane Fractions Under Biochemical and Endogenous Sterol Depletion*

PubMed Central

Zauber, Henrik; Szymanski, Witold; Schulze, Waltraud X.

2013-01-01

During the last decade, research on plasma membrane focused increasingly on the analysis of so-called microdomains. It has been shown that function of many membrane-associated proteins involved in signaling and transport depends on their conditional segregation within sterol-enriched membrane domains. High throughput proteomic analysis of sterol-protein interactions are often based on analyzing detergent resistant membrane fraction enriched in sterols and associated proteins, which also contain proteins from these microdomain structures. Most studies so far focused exclusively on the characterization of detergent resistant membrane protein composition and abundances. This approach has received some criticism because of its unspecificity and many co-purifying proteins. In this study, by a label-free quantitation approach, we extended the characterization of membrane microdomains by particularly studying distributions of each protein between detergent resistant membrane and detergent-soluble fractions (DSF). This approach allows a more stringent definition of dynamic processes between different membrane phases and provides a means of identification of co-purifying proteins. We developed a random sampling algorithm, called Unicorn, allowing for robust statistical testing of alterations in the protein distribution ratios of the two different fractions. Unicorn was validated on proteomic data from methyl-β-cyclodextrin treated plasma membranes and the sterol biosynthesis mutant smt1. Both, chemical treatment and sterol-biosynthesis mutation affected similar protein classes in their membrane phase distribution and particularly proteins with signaling and transport functions. PMID:24030099

Distribution of thiobarbituric acid-reactive substances in lipoproteins and proteins in serum.

PubMed

Bonnefont, D; Legrand, A; Peynet, J; Emerit, J; Delattre, J; Galli, A

1989-10-01

We assessed the distribution of malondialdehyde (MDA) in lipoproteins and proteins in serum after using two procedures to separate the lipoproteins: sequential ultracentrifugation or selective precipitation with a sodium phosphotungstate and magnesium chloride reagent followed by ultracentrifugation of the supernate. MDA concentrations were determined by the thiobarbituric acid reaction and quantified by fluorometry. We found that 43% of the thiobarbituric acid-reactive substances (TBARS) was bound to the lipoproteins--27% to very-low- and low-density lipoproteins (VLDL-LDL) and 16% to high-density lipoproteins (HDL)--and from 11.5% to 15.8% to proteins, depending on the separation procedure. Residual unbound TBARS were located in the ultracentrifugation layers that contained no lipoproteins or proteins. The TBARS concentration in serum lipoproteins containing apolipoprotein B (i.e., VLDL-LDL) was the same after ultracentrifugation or selective precipitation. We therefore consider the precipitation method more suitable for routine TBARS determination in these lipoproteins, because it is easier to handle and faster. However, for determination of TBARS in HDL, selective precipitation requires subsequent ultracentrifugation at a density of 1.21 kg/L.

DriveWise: An Interdisciplinary Hospital-Based Driving Assessment Program

ERIC Educational Resources Information Center

O'Connor, Margaret G.; Kapust, Lissa R.; Hollis, Ann M.

2008-01-01

Health care professionals working with the elderly have opportunities through research and clinical practice to shape public policy affecting the older driver. This article describes DriveWise, an interdisciplinary hospital-based driving assessment program developed in response to clinical concerns about the driving safety of individuals with…

Life at the border: Adaptation of proteins to anisotropic membrane environment

PubMed Central

Pogozheva, Irina D; Mosberg, Henry I; Lomize, Andrei L

2014-01-01

This review discusses main features of transmembrane (TM) proteins which distinguish them from water-soluble proteins and allow their adaptation to the anisotropic membrane environment. We overview the structural limitations on membrane protein architecture, spatial arrangement of proteins in membranes and their intrinsic hydrophobic thickness, co-translational and post-translational folding and insertion into lipid bilayers, topogenesis, high propensity to form oligomers, and large-scale conformational transitions during membrane insertion and transport function. Special attention is paid to the polarity of TM protein surfaces described by profiles of dipolarity/polarizability and hydrogen-bonding capacity parameters that match polarity of the lipid environment. Analysis of distributions of Trp resides on surfaces of TM proteins from different biological membranes indicates that interfacial membrane regions with preferential accumulation of Trp indole rings correspond to the outer part of the lipid acyl chain region—between double bonds and carbonyl groups of lipids. These “midpolar” regions are not always symmetric in proteins from natural membranes. We also examined the hydrophobic effect that drives insertion of proteins into lipid bilayer and different free energy contributions to TM protein stability, including attractive van der Waals forces and hydrogen bonds, side-chain conformational entropy, the hydrophobic mismatch, membrane deformations, and specific protein–lipid binding. PMID:24947665

A tyre slip-based integrated chassis control of front/rear traction distribution and four-wheel independent brake from moderate driving to limit handling

NASA Astrophysics Data System (ADS)

Joa, Eunhyek; Park, Kwanwoo; Koh, Youngil; Yi, Kyongsu; Kim, Kilsoo

2018-04-01

This paper presents a tyre slip-based integrated chassis control of front/rear traction distribution and four-wheel braking for enhanced performance from moderate driving to limit handling. The proposed algorithm adopted hierarchical structure: supervisor - desired motion tracking controller - optimisation-based control allocation. In the supervisor, by considering transient cornering characteristics, desired vehicle motion is calculated. In the desired motion tracking controller, in order to track desired vehicle motion, virtual control input is determined in the manner of sliding mode control. In the control allocation, virtual control input is allocated to minimise cost function. The cost function consists of two major parts. First part is a slip-based tyre friction utilisation quantification, which does not need a tyre force estimation. Second part is an allocation guideline, which guides optimally allocated inputs to predefined solution. The proposed algorithm has been investigated via simulation from moderate driving to limit handling scenario. Compared to Base and direct yaw moment control system, the proposed algorithm can effectively reduce tyre dissipation energy in the moderate driving situation. Moreover, the proposed algorithm enhances limit handling performance compared to Base and direct yaw moment control system. In addition to comparison with Base and direct yaw moment control, comparison the proposed algorithm with the control algorithm based on the known tyre force information has been conducted. The results show that the performance of the proposed algorithm is similar with that of the control algorithm with the known tyre force information.

Self-regulation of driving and its relationship to driving ability among older adults.

PubMed

Baldock, M R J; Mathias, J L; McLean, A J; Berndt, A

2006-09-01

Although it is known that older drivers limit their driving, it is not known whether this self-regulation is related to actual driving ability. A sample of 104 older drivers, aged between 60 and 92, completed a questionnaire about driving habits and attitudes. Ninety of these drivers also completed a structured on-road driving test. A measure of self-regulation was derived from drivers' self-reported avoidance of difficult driving situations. The on-road driving test involved a standard assessment used to determine fitness to drive. Driving test scores for the study were based on the number of errors committed in the driving tests, with weightings given according to the seriousness of the errors. The most commonly avoided difficult driving situations, according to responses on the questionnaire, were parallel parking and driving at night in the rain, while the least avoided situation was driving alone. Poorer performance on the driving test was not related to overall avoidance of difficult driving situations. Stronger relationships were found between driving ability and avoidance of specific difficult driving situations. These specific driving situations were the ones in which the drivers had low confidence and that the drivers were most able to avoid if they wished to.

Selection on Network Dynamics Drives Differential Rates of Protein Domain Evolution

PubMed Central

Mannakee, Brian K.; Gutenkunst, Ryan N.

2016-01-01

The long-held principle that functionally important proteins evolve slowly has recently been challenged by studies in mice and yeast showing that the severity of a protein knockout only weakly predicts that protein’s rate of evolution. However, the relevance of these studies to evolutionary changes within proteins is unknown, because amino acid substitutions, unlike knockouts, often only slightly perturb protein activity. To quantify the phenotypic effect of small biochemical perturbations, we developed an approach to use computational systems biology models to measure the influence of individual reaction rate constants on network dynamics. We show that this dynamical influence is predictive of protein domain evolutionary rate within networks in vertebrates and yeast, even after controlling for expression level and breadth, network topology, and knockout effect. Thus, our results not only demonstrate the importance of protein domain function in determining evolutionary rate, but also the power of systems biology modeling to uncover unanticipated evolutionary forces. PMID:27380265

Older driver fitness-to-drive evaluation using naturalistic driving data.

PubMed

Guo, Feng; Fang, Youjia; Antin, Jonathan F

2015-09-01

As our driving population continues to age, it is becoming increasingly important to find a small set of easily administered fitness metrics that can meaningfully and reliably identify at-risk seniors requiring more in-depth evaluation of their driving skills and weaknesses. Sixty driver assessment metrics related to fitness-to-drive were examined for 20 seniors who were followed for a year using the naturalistic driving paradigm. Principal component analysis and negative binomial regression modeling approaches were used to develop parsimonious models relating the most highly predictive of the driver assessment metrics to the safety-related outcomes observed in the naturalistic driving data. This study provides important confirmation using naturalistic driving methods of the relationship between contrast sensitivity and crash-related events. The results of this study provide crucial information on the continuing journey to identify metrics and protocols that could be applied to determine seniors' fitness to drive. Published by Elsevier Ltd.

On the influence of the mixture of denaturants on protein structure stability: A molecular dynamics study

NASA Astrophysics Data System (ADS)

Shao, Qiang; Wang, Jinan; Zhu, Weiliang

2014-09-01

Mixtures of osmolytes and/or inorganic salts are present in the cell. Therefore, the understanding of the interplay of mixed osmolyte molecules and inorganic salts and their combined effects on protein structure is of fundamental importance. A novel test is presented to investigate the combined effects of urea and a chaotropic inorganic salt, potassium iodide (KI), on protein structure by using molecular dynamics simulation. It is found that the coexistence of KI and urea does not affect their respective distribution in solution. The solvation of KI salt in urea solution makes the electrostatic interactions of urea more favorable, promoting the hydrogen bonding between urea (and water) to protein backbone. The interactions from K+ and hydrogen bonding from urea and water to protein backbone work as the driving force for protein denaturation. The collaborative behavior of urea and KI salt thus enhances the denaturing ability of urea and KI mixed solution.

DriveSafe and DriveAware Assessment Tools Are a Measure of Driving-Related Function and Predicts Self-Reported Restriction for Older Drivers.

PubMed

Allan, Claire; Coxon, Kristy; Bundy, Anita; Peattie, Laura; Keay, Lisa

2016-06-01

Safety concerns together with aging of the driving population has prompted research into clinic-based driving assessments. This study investigates the relationship between the DriveSafe and DriveAware assessments and restriction of driving. Community-dwelling adults aged more than 75 (n = 380) were recruited in New South Wales, Australia. Questionnaires were administered to assess driving habits and functional assessments to assess driving-related function. Self-reported restriction was prevalent in this cross-sectional sample (62%) and was related to DriveSafe scores and personal circumstances but not DriveAware scores. DriveSafe scores were correlated with better performance on the Trail-Making Test (TMT; β = -2.94, p < .0001) and better contrast sensitivity (β = 48.70, p < .0001). Awareness was associated with better performance on the TMT (β = 0.08, p < .0001). Our data suggest that DriveSafe and DriveAware are sensitive to deficits in vision and cognition, and drivers with worse DriveSafe scores self-report restricting their driving. © The Author(s) 2015.

The Attentional Demand of Automobile Driving Revisited: Occlusion Distance as a Function of Task-Relevant Event Density in Realistic Driving Scenarios.

PubMed

Kujala, Tuomo; Mäkelä, Jakke; Kotilainen, Ilkka; Tokkonen, Timo

2016-02-01

We studied the utility of occlusion distance as a function of task-relevant event density in realistic traffic scenarios with self-controlled speed. The visual occlusion technique is an established method for assessing visual demands of driving. However, occlusion time is not a highly informative measure of environmental task-relevant event density in self-paced driving scenarios because it partials out the effects of changes in driving speed. Self-determined occlusion times and distances of 97 drivers with varying backgrounds were analyzed in driving scenarios simulating real Finnish suburban and highway traffic environments with self-determined vehicle speed. Occlusion distances varied systematically with the expected environmental demands of the manipulated driving scenarios whereas the distributions of occlusion times remained more static across the scenarios. Systematic individual differences in the preferred occlusion distances were observed. More experienced drivers achieved better lane-keeping accuracy than inexperienced drivers with similar occlusion distances; however, driving experience was unexpectedly not a major factor for the preferred occlusion distances. Occlusion distance seems to be an informative measure for assessing task-relevant event density in realistic traffic scenarios with self-controlled speed. Occlusion time measures the visual demand of driving as the task-relevant event rate in time intervals, whereas occlusion distance measures the experienced task-relevant event density in distance intervals. The findings can be utilized in context-aware distraction mitigation systems, human-automated vehicle interaction, road speed prediction and design, as well as in the testing of visual in-vehicle tasks for inappropriate in-vehicle glancing behaviors in any dynamic traffic scenario for which appropriate individual occlusion distances can be defined. © 2015, Human Factors and Ergonomics Society.

Parental perceptions of teen driving: Restrictions, worry and influence.

PubMed

Jewett, Amy; Shults, Ruth A; Bhat, Geeta

2016-12-01

Parents play a critical role in preventing crashes among teens. Research of parental perceptions and concerns regarding teen driving safety is limited. We examined results from the 2013 Summer ConsumerStyles survey that queried parents about restrictions placed on their teen drivers, their perceived level of "worry" about their teen driver's safety, and influence of parental restrictions regarding their teen's driving. We produced frequency distributions for the number of restrictions imposed, parental "worry," and influence of rules regarding their teen's driving, reported by teen's driving license status (learning to drive or obtained a driver's license). Response categories were dichotomized because of small cell sizes, and we ran separate log-linear regression models to explore whether imposing all four restrictions on teen drivers was associated with either worry intensity ("a lot" versus "somewhat, not very much or not at all") or perceived influence of parental rules ("a lot" versus "somewhat, not very much or not at all"). Among the 456 parent respondents, 80% reported having restrictions for their teen driver regarding use of safety belts, drinking and driving, cell phones, and text messaging while driving. However, among the 188 parents of licensed teens, only 9% reported having a written parent-teen driving agreement, either currently or in the past. Worrying "a lot" was reported less frequently by parents of newly licensed teens (36%) compared with parents of learning teens (61%). Parents report having rules and restrictions for their teen drivers, but only a small percentage formalize the rules and restrictions in a written parent-teen driving agreement. Parents worry less about their teen driver's safety during the newly licensed phase, when crash risk is high as compared to the learning phase. Further research is needed into how to effectively support parents in supervising and monitoring their teen driver. Published by Elsevier Ltd.

Computational Analysis of the Caenorhabditis elegans Germline to Study the Distribution of Nuclei, Proteins, and the Cytoskeleton.

PubMed

Gopal, Sandeep; Pocock, Roger

2018-04-19

The Caenorhabditis elegans (C. elegans) germline is used to study several biologically important processes including stem cell development, apoptosis, and chromosome dynamics. While the germline is an excellent model, the analysis is often two dimensional due to the time and labor required for three-dimensional analysis. Major readouts in such studies are the number/position of nuclei and protein distribution within the germline. Here, we present a method to perform automated analysis of the germline using confocal microscopy and computational approaches to determine the number and position of nuclei in each region of the germline. Our method also analyzes germline protein distribution that enables the three-dimensional examination of protein expression in different genetic backgrounds. Further, our study shows variations in cytoskeletal architecture in distinct regions of the germline that may accommodate specific spatial developmental requirements. Finally, our method enables automated counting of the sperm in the spermatheca of each germline. Taken together, our method enables rapid and reproducible phenotypic analysis of the C. elegans germline.

Pile Driving

NASA Technical Reports Server (NTRS)

1987-01-01

Machine-oriented structural engineering firm TERA, Inc. is engaged in a project to evaluate the reliability of offshore pile driving prediction methods to eventually predict the best pile driving technique for each new offshore oil platform. Phase I Pile driving records of 48 offshore platforms including such information as blow counts, soil composition and pertinent construction details were digitized. In Phase II, pile driving records were statistically compared with current methods of prediction. Result was development of modular software, the CRIPS80 Software Design Analyzer System, that companies can use to evaluate other prediction procedures or other data bases.

Direct Drive Hall Thruster System Development

NASA Technical Reports Server (NTRS)

Hoskins, W. Andrew; Homiak, Daniel; Cassady, R. Joseph; Kerslake, Tom; Peterson, Todd; Ferguson, Dale; Snyder, Dave; Mikellides, Ioannis; Jongeward, Gary; Schneider, Todd

2003-01-01

The sta:us of development of a Direct Drive Ha!! Thruster System is presented. 13 the first part. a s:udy of the impacts to spacecraft systems and mass benefits of a direct-drive architecture is reviewed. The study initially examines four cases of SPT-100 and BPT-4000 Hall thrusters used for north-south station keeping on an EXPRESS-like geosynchronous spacecraft and for primary propulsion for a Deep Space- 1 based science spacecraft. The study is also extended the impact of direct drive on orbit raising for higher power geosynchronous spacecraft and on other deep space missions as a function of power and delta velocity. The major system considerations for accommodating a direct drive Hall thruster are discussed, including array regulation, system grounding, distribution of power to the spacecraft bus, and interactions between current-voltage characteristics for the arrays and thrusters. The mass benefit analysis shows that, for the initial cases, up to 42 kg of dry mass savings is attributable directly to changes in the propulsion hardware. When projected mass impacts of operating the arrays and the electric power system at 300V are included, up to 63 kg is saved for the four initial cases. Adoption of high voltage lithium ion battery technology is projected to further improve these savings. Orbit raising of higher powered geosynchronous spacecraft, is the mission for which direct drive provides the most benefit, allowing higher efficiency electric orbit raising to be accomplished in a limited period of time, as well as nearly eliminating significant power processing heat rejection mass. The total increase in useful payload to orbit ranges up to 278 kg for a 25 kW spacecraft, launched from an Atlas IIA. For deep space missions, direct drive is found to be most applicable to higher power missions with delta velocities up to several km/s , typical of several Discovery-class missions. In the second part, the status of development of direct drive propulsion power

Electronic distributions within protein phenylalanine aromatic rings are reflected by the three-dimensional oxygen atom environments.

PubMed Central

Thomas, K A; Smith, G M; Thomas, T B; Feldmann, R J

1982-01-01

The atomic environments of 170 phenylalanine-residue aromatic rings from 28 protein crystal structures are transformed into a common orientation and combined to calculate an average three-dimensional environment. The spatial distribution of atom types in this environment reveals a preferred interaction between oxygen atoms and the edge of the planar aromatic rings. From the difference in frequency of interaction of oxygen atoms with the edge and the top of the ring, an apparent net free energy difference of interaction favoring the edge of the ring is estimated to be about -1 kcal/mol (1 cal = 4.184 J). Ab initio quantum mechanical calculations, performed on a model consisting of benzene and formamide, indicate that the observed geometry is stabilized by a favorable enthalpic interaction. Although benzene rings are considered to be nonpolar, the electron distribution is a complex multipole with no net dipole moment. The observed interaction orientation frequencies demonstrate that these multipolar electron distributions, when occurring at the short distances encountered in densely packed protein molecules, are significant determinants of internal packing geometries. PMID:6956896

Robust co-regulation of tyrosine phosphorylation sites on proteins reveals novel protein interactions†

PubMed Central

Naegle, Kristen M.; White, Forest M.; Lauffenburger, Douglas A.; Yaffe, Michael B.

2012-01-01

Cell signaling networks propagate information from extracellular cues via dynamic modulation of protein–protein interactions in a context-dependent manner. Networks based on receptor tyrosine kinases (RTKs), for example, phosphorylate intracellular proteins in response to extracellular ligands, resulting in dynamic protein–protein interactions that drive phenotypic changes. Most commonly used methods for discovering these protein–protein interactions, however, are optimized for detecting stable, longer-lived complexes, rather than the type of transient interactions that are essential components of dynamic signaling networks such as those mediated by RTKs. Substrate phosphorylation downstream of RTK activation modifies substrate activity and induces phospho-specific binding interactions, resulting in the formation of large transient macromolecular signaling complexes. Since protein complex formation should follow the trajectory of events that drive it, we reasoned that mining phosphoproteomic datasets for highly similar dynamic behavior of measured phosphorylation sites on different proteins could be used to predict novel, transient protein–protein interactions that had not been previously identified. We applied this method to explore signaling events downstream of EGFR stimulation. Our computational analysis of robustly co-regulated phosphorylation sites, based on multiple clustering analysis of quantitative time-resolved mass-spectrometry phosphoproteomic data, not only identified known sitewise-specific recruitment of proteins to EGFR, but also predicted novel, a priori interactions. A particularly intriguing prediction of EGFR interaction with the cytoskeleton-associated protein PDLIM1 was verified within cells using co-immunoprecipitation and in situ proximity ligation assays. Our approach thus offers a new way to discover protein–protein interactions in a dynamic context- and phosphorylation site-specific manner. PMID:22851037

Driving Safety and Fitness to Drive in Sleep Disorders.

PubMed

Tippin, Jon; Dyken, Mark Eric

2017-08-01

Driving an automobile while sleepy increases the risk of crash-related injury and death. Neurologists see patients with sleepiness due to obstructive sleep apnea, narcolepsy, and a wide variety of neurologic disorders. When addressing fitness to drive, the physician must weigh patient and societal health risks and regional legal mandates. The Driver Fitness Medical Guidelines published by the National Highway Traffic Safety Administration (NHTSA) and the American Association of Motor Vehicle Administrators (AAMVA) provide assistance to clinicians. Drivers with obstructive sleep apnea may continue to drive if they have no excessive daytime sleepiness and their apnea-hypopnea index is less than 20 per hour. Those with excessive daytime sleepiness or an apnea-hypopnea index of 20 per hour or more may not drive until their condition is effectively treated. Drivers with sleep disorders amenable to pharmaceutical treatment (eg, narcolepsy) may resume driving as long as the therapy has eliminated excessive daytime sleepiness. Following these guidelines, documenting compliance to recommended therapy, and using the Epworth Sleepiness Scale to assess subjective sleepiness can be helpful in determining patients' fitness to drive.

A practical large scale/high speed data distribution system using 8 mm libraries

NASA Technical Reports Server (NTRS)

Howard, Kevin

1993-01-01

Eight mm tape libraries are known primarily for their small size, large storage capacity, and low cost. However, many applications require an additional attribute which, heretofore, has been lacking -- high transfer rate. Transfer rate is particularly important in a large scale data distribution environment -- an environment in which 8 mm tape should play a very important role. Data distribution is a natural application for 8 mm for several reasons: most large laboratories have access to 8 mm tape drives, 8 mm tapes are upwardly compatible, 8 mm media are very inexpensive, 8 mm media are light weight (important for shipping purposes), and 8 mm media densely pack data (5 gigabytes now and 15 gigabytes on the horizon). If the transfer rate issue were resolved, 8 mm could offer a good solution to the data distribution problem. To that end Exabyte has analyzed four ways to increase its transfer rate: native drive transfer rate increases, data compression at the drive level, tape striping, and homogeneous drive utilization. Exabyte is actively pursuing native drive transfer rate increases and drive level data compression. However, for non-transmitted bulk data applications (which include data distribution) the other two methods (tape striping and homogeneous drive utilization) hold promise.

The WD40 Protein BamB Mediates Coupling of BAM Complexes into Assembly Precincts in the Bacterial Outer Membrane.

PubMed

Gunasinghe, Sachith D; Shiota, Takuya; Stubenrauch, Christopher J; Schulze, Keith E; Webb, Chaille T; Fulcher, Alex J; Dunstan, Rhys A; Hay, Iain D; Naderer, Thomas; Whelan, Donna R; Bell, Toby D M; Elgass, Kirstin D; Strugnell, Richard A; Lithgow, Trevor

2018-05-29

The β-barrel assembly machinery (BAM) complex is essential for localization of surface proteins on bacterial cells, but the mechanism by which it functions is unclear. We developed a direct stochastic optical reconstruction microscopy (dSTORM) methodology to view the BAM complex in situ. Single-cell analysis showed that discrete membrane precincts housing several BAM complexes are distributed across the E. coli surface, with a nearest neighbor distance of ∼200 nm. The auxiliary lipoprotein subunit BamB was crucial for this spatial distribution, and in situ crosslinking shows that BamB makes intimate contacts with BamA and BamB in neighboring BAM complexes within the precinct. The BAM complex precincts swell when outer membrane protein synthesis is maximal, visual proof that the precincts are active in protein assembly. This nanoscale interrogation of the BAM complex in situ suggests a model whereby bacterial outer membranes contain highly organized assembly precincts to drive integral protein assembly. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Protein-Protein Interaction Site Predictions with Three-Dimensional Probability Distributions of Interacting Atoms on Protein Surfaces

PubMed Central

Chen, Ching-Tai; Peng, Hung-Pin; Jian, Jhih-Wei; Tsai, Keng-Chang; Chang, Jeng-Yih; Yang, Ei-Wen; Chen, Jun-Bo; Ho, Shinn-Ying; Hsu, Wen-Lian; Yang, An-Suei

2012-01-01

Protein-protein interactions are key to many biological processes. Computational methodologies devised to predict protein-protein interaction (PPI) sites on protein surfaces are important tools in providing insights into the biological functions of proteins and in developing therapeutics targeting the protein-protein interaction sites. One of the general features of PPI sites is that the core regions from the two interacting protein surfaces are complementary to each other, similar to the interior of proteins in packing density and in the physicochemical nature of the amino acid composition. In this work, we simulated the physicochemical complementarities by constructing three-dimensional probability density maps of non-covalent interacting atoms on the protein surfaces. The interacting probabilities were derived from the interior of known structures. Machine learning algorithms were applied to learn the characteristic patterns of the probability density maps specific to the PPI sites. The trained predictors for PPI sites were cross-validated with the training cases (consisting of 432 proteins) and were tested on an independent dataset (consisting of 142 proteins). The residue-based Matthews correlation coefficient for the independent test set was 0.423; the accuracy, precision, sensitivity, specificity were 0.753, 0.519, 0.677, and 0.779 respectively. The benchmark results indicate that the optimized machine learning models are among the best predictors in identifying PPI sites on protein surfaces. In particular, the PPI site prediction accuracy increases with increasing size of the PPI site and with increasing hydrophobicity in amino acid composition of the PPI interface; the core interface regions are more likely to be recognized with high prediction confidence. The results indicate that the physicochemical complementarity patterns on protein surfaces are important determinants in PPIs, and a substantial portion of the PPI sites can be predicted correctly with

Driving Performance Under Alcohol in Simulated Representative Driving Tasks

PubMed Central

Kenntner-Mabiala, Ramona; Kaussner, Yvonne; Jagiellowicz-Kaufmann, Monika; Hoffmann, Sonja; Krüger, Hans-Peter

2015-01-01

Abstract Comparing drug-induced driving impairments with the effects of benchmark blood alcohol concentrations (BACs) is an approved approach to determine the clinical relevance of findings for traffic safety. The present study aimed to collect alcohol calibration data to validate findings of clinical trials that were derived from a representative test course in a dynamic driving simulator. The driving performance of 24 healthy volunteers under placebo and with 0.05% and 0.08% BACs was measured in a double-blind, randomized, crossover design. Trained investigators assessed the subjects’ driving performance and registered their driving errors. Various driving parameters that were recorded during the simulation were also analyzed. Generally, the participants performed worse on the test course (P < 0.05 for the investigators’ assessment) under the influence of alcohol. Consistent with the relevant literature, lane-keeping performance parameters were sensitive to the investigated BACs. There were significant differences between the alcohol and placebo conditions in most of the parameters analyzed. However, the total number of errors was the only parameter discriminating significantly between all three BAC conditions. In conclusion, data show that the present experimental setup is suitable for future psychopharmacological research. Thereby, for each drug to be investigated, we recommend to assess a profile of various parameters that address different levels of driving. On the basis of this performance profile, the total number of driving errors is recommended as the primary endpoint. However, this overall endpoint should be completed by a specifically sensitive parameter that is chosen depending on the effect known to be induced by the tested drug. PMID:25689289

Distribution of monoamine oxidase proteins in human brain: implications for brain imaging studies

PubMed Central

Tong, Junchao; Meyer, Jeffrey H; Furukawa, Yoshiaki; Boileau, Isabelle; Chang, Li-Jan; Wilson, Alan A; Houle, Sylvain; Kish, Stephen J

2013-01-01

Positron emission tomography (PET) imaging of monoamine oxidases (MAO-A: [11C]harmine, [11C]clorgyline, and [11C]befloxatone; MAO-B: [11C]deprenyl-D2) has been actively pursued given clinical importance of MAOs in human neuropsychiatric disorders. However, it is unknown how well PET outcome measures for the different radiotracers are quantitatively related to actual MAO protein levels. We measured regional distribution (n=38) and developmental/aging changes (21 hours to 99 years) of both MAOs by quantitative immunoblotting in autopsied normal human brain. MAO-A was more abundant than MAO-B in infants, which was reversed as MAO-B levels increased faster before 1 year and, unlike MAO-A, kept increasing steadily to senescence. In adults, regional protein levels of both MAOs were positively and proportionally correlated with literature postmortem data of MAO activities and binding densities. With the exception of [11C]befloxatone (binding potential (BP), r=0.61, P=0.15), correlations between regional PET outcome measures of binding in the literature and MAO protein levels were good (P<0.01) for [11C]harmine (distribution volume, r=0.86), [11C]clorgyline (λk3, r=0.82), and [11C]deprenyl-D2 (λk3 or modified Patlak slope, r=0.78 to 0.87), supporting validity of the latter imaging measures. However, compared with in vitro data, the latter PET measures underestimated regional contrast by ∼2-fold. Further studies are needed to address cause of the in vivo vs. in vitro nonproportionality. PMID:23403377

Sex drives intracellular conflict in yeast.

PubMed

Harrison, E; MacLean, R C; Koufopanou, V; Burt, A

2014-08-01

Theory predicts that sex can drive the evolution of conflict within the cell. During asexual reproduction, genetic material within the cell is inherited as a single unit, selecting for cooperation both within the genome as well as between the extra-genomic elements within the cell (e.g. plasmids and endosymbionts). Under sexual reproduction, this unity is broken down as parental genomes are distributed between meiotic progeny. Genetic elements able to transmit to more than 50% of meiotic progeny have a transmission advantage over the rest of the genome and are able to spread, even where they reduce the fitness of the individual as a whole. Sexual reproduction is therefore expected to drive the evolution of selfish genetic elements (SGEs). Here, we directly test this hypothesis by studying the evolution of two independent SGEs, the 2-μm plasmid and selfish mitochondria, in populations of Saccharomyces cerevisiae. Following 22 rounds of sexual reproduction, 2-μm copy number increased by approximately 13.2 (±5.6) copies per cell, whereas in asexual populations copy number decreased by approximately 5.1 (±1.5) copies per cell. Given that the burden imposed by this parasite increases with copy number, these results support the idea that sex drives the evolution of increased SGE virulence. Moreover, we found that mitochondria that are respiratory-deficient rapidly invaded sexual but not asexual populations, demonstrating that frequent outcrossed sex can drive the de novo evolution of genetic parasites. Our study highlights the genomic perils of sex and suggests that SGEs may play a key role in driving major evolutionary transitions, such as uniparental inheritance. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

Molecular simulations of lipid-mediated protein-protein interactions.

PubMed

de Meyer, Frédérick Jean-Marie; Venturoli, Maddalena; Smit, Berend

2008-08-01

Recent experimental results revealed that lipid-mediated interactions due to hydrophobic forces may be important in determining the protein topology after insertion in the membrane, in regulating the protein activity, in protein aggregation and in signal transduction. To gain insight into the lipid-mediated interactions between two intrinsic membrane proteins, we developed a mesoscopic model of a lipid bilayer with embedded proteins, which we studied with dissipative particle dynamics. Our calculations of the potential of mean force between transmembrane proteins show that hydrophobic forces drive long-range protein-protein interactions and that the nature of these interactions depends on the length of the protein hydrophobic segment, on the three-dimensional structure of the protein and on the properties of the lipid bilayer. To understand the nature of the computed potentials of mean force, the concept of hydrophilic shielding is introduced. The observed protein interactions are interpreted as resulting from the dynamic reorganization of the system to maintain an optimal hydrophilic shielding of the protein and lipid hydrophobic parts, within the constraint of the flexibility of the components. Our results could lead to a better understanding of several membrane processes in which protein interactions are involved.

Modelling of DNA-Mediated of Two- and -Three dimensional Protein-Protein and Protein-Nanoparticle Self-Assembly

NASA Astrophysics Data System (ADS)

Millan, Jaime; McMillan, Janet; Brodin, Jeff; Lee, Byeongdu; Mirkin, Chad; Olvera de La Cruz, Monica

Programmable DNA interactions represent a robust scheme to self-assemble a rich variety of tunable superlattices, where intrinsic and in some cases non-desirable nano-scale building blocks interactions are substituted for DNA hybridization events. Recent advances in synthesis has allowed the extension of this successful scheme to proteins, where DNA distribution can be tuned independently of protein shape by selectively addressing surface residues, giving rise to assembly properties in three dimensional protein-nanoparticle superlattices dependent on DNA distribution. In parallel to this advances, we introduced a scalable coarse-grained model that faithfully reproduces the previously observed co-assemblies from nanoparticles and proteins conjugates. Herein, we implement this numerical model to explain the stability of complex protein-nanoparticle binary superlattices and to elucidate experimentally inaccessible features such as protein orientation. Also, we will discuss systematic studies that highlight the role of DNA distribution and sequence on two-dimensional protein-protein and protein-nanoparticle superlattices.

Environmental characteristics drive variation in Amazonian understorey bird assemblages

PubMed Central

Magnusson, William E.; Anderson, Marti J.; Schlegel, Martin; Pe’er, Guy; Henle, Klaus

2017-01-01

Tropical bird assemblages display patterns of high alpha and beta diversity and, as tropical birds exhibit strong habitat specificity, their spatial distributions are generally assumed to be driven primarily by environmental heterogeneity and interspecific interactions. However, spatial distributions of some Amazonian forest birds are also often restricted by large rivers and other large-scale topographic features, suggesting that dispersal limitation may also play a role in driving species’ turnover. In this study, we evaluated the effects of environmental characteristics, topographic and spatial variables on variation in local assemblage structure and diversity of birds in an old-growth forest in central Amazonia. Birds were mist-netted in 72 plots distributed systematically across a 10,000 ha reserve in each of three years. Alpha diversity remained stable through time, but species composition changed. Spatial variation in bird-assemblage structure was significantly related to environmental and topographic variables but not strongly related to spatial variables. At a broad scale, we found bird assemblages to be significantly distinct between two watersheds that are divided by a central ridgeline. We did not detect an effect of the ridgeline per se in driving these patterns, indicating that most birds are able to fly across it, and that differences in assemblage structure between watersheds may be due to unmeasured environmental variables or unique combinations of measured variables. Our study indicates that complex geography and landscape features can act together with environmental variables to drive changes in the diversity and composition of tropical bird assemblages at local scales, but highlights that we still know very little about what makes different parts of tropical forest suitable for different species. PMID:28225774

The impact of particle preparation methods and polymorphic stability of lipid excipients on protein distribution in microparticles.

PubMed

Liu, Jingying; Christophersen, Philip C; Yang, Mingshi; Nielsen, Hanne M; Mu, Huiling

2017-12-01

The present study aimed at elucidating the influence of polymorphic stability of lipid excipients on the physicochemical characters of different solid lipid microparticles (SLM), with the focus on the alteration of protein distribution in SLM. Labeled lysozyme was incorporated into SLM prepared with different excipients, i.e. trimyristin (TG14), glyceryl distearate (GDS), and glyceryl monostearate (GMS), by water-oil-water (w/o/w) or solid-oil-water (s/o/w) method. The distribution of lysozyme in SLM and the release of the protein from SLM were evaluated by confocal laser scanning microscopy. The storage stability of SLM was characterized by HPLC, differential scanning calorimetry, X-ray powder diffraction, and scanning electron microscopy. Lysozyme was displayed as small scattered domains inside GDS and GMS SLM, whereas it was incorporated in the core of TG14 SLM formulated by the w/o/w method or evenly distributed in TG14 SLM prepared by the s/o/w method. Stability study at 37 °C revealed that only TG14 SLM made by the w/o/w method was able to maintain the lysozyme amount both on the particle surface and released from the SLM. Elevated storage temperature induced polymorphic transition of lipids in GDS and GMS SLM, which was, however, not remarkable for the TG14 SLM. Lipid excipients and particle preparation methods were found to differently affect the lysozyme distribution in SLM, owning to varied storage stabilities of the lipids. The present study provides updated knowledge for rational development of lipid-based formulations for oral delivery of peptide or protein drugs.

Hendra virus fusion protein transmembrane domain contributes to pre-fusion protein stability

PubMed Central

Webb, Stacy; Nagy, Tamas; Moseley, Hunter; Fried, Michael; Dutch, Rebecca

2017-01-01

Enveloped viruses utilize fusion (F) proteins studding the surface of the virus to facilitate membrane fusion with a target cell membrane. Fusion of the viral envelope with a cellular membrane is required for release of viral genomic material, so the virus can ultimately reproduce and spread. To drive fusion, the F protein undergoes an irreversible conformational change, transitioning from a metastable pre-fusion conformation to a more thermodynamically stable post-fusion structure. Understanding the elements that control stability of the pre-fusion state and triggering to the post-fusion conformation is important for understanding F protein function. Mutations in F protein transmembrane (TM) domains implicated the TM domain in the fusion process, but the structural and molecular details in fusion remain unclear. Previously, analytical ultracentrifugation was utilized to demonstrate that isolated TM domains of Hendra virus F protein associate in a monomer-trimer equilibrium (Smith, E. C., Smith, S. E., Carter, J. R., Webb, S. R., Gibson, K. M., Hellman, L. M., Fried, M. G., and Dutch, R. E. (2013) J. Biol. Chem. 288, 35726–35735). To determine factors driving this association, 140 paramyxovirus F protein TM domain sequences were analyzed. A heptad repeat of β-branched residues was found, and analysis of the Hendra virus F TM domain revealed a heptad repeat leucine-isoleucine zipper motif (LIZ). Replacement of the LIZ with alanine resulted in dramatically reduced TM-TM association. Mutation of the LIZ in the whole protein resulted in decreased protein stability, including pre-fusion conformation stability. Together, our data suggest that the heptad repeat LIZ contributed to TM-TM association and is important for F protein function and pre-fusion stability. PMID:28213515

Patch Network for Power Allocation and Distribution in Smart Materials

NASA Technical Reports Server (NTRS)

Golembiewski, Walter T.

2000-01-01

The power allocation and distribution (PAD) circuitry is capable of allocating and distributing a single or multiple sources of power over multi-elements of a power user grid system. The purpose of this invention is to allocate and distribute power that is collected by individual patch rectennas to a region of specific power-user devices, such as actuators. The patch rectenna converts microwave power into DC power. Then this DC power is used to drive actuator devices. However, the power from patch rectennas is not sufficient to drive actuators unless all the collected power is effectively used to drive another group by allocation and distribution. The power allocation and distribution (PAD) circuitry solves the shortfall of power for devices in a large array. The PAD concept is based on the networked power control in which power collected over the whole array of rectennas is allocated to a sub domain where a group of devices is required to be activated for operation. Then the allocated power is distributed to individual element of power-devices in the sub domain according to a selected run-mode.

Regional distribution and subcellular associations of Type II calcium and calmodulin-dependent protein kinase in rat brain

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

Erondu, N.E.

1986-01-01

Four monoclonal antibodies generated against the Type II CaM kinase have been characterized. Two of these antibodies were used to confirm that both alpha and beta subunits were part of the holoenzyme complex. I also developed liquid phase and solid phase radioimmunoassays for the kinase. With the solid phase radioimmunoassay, the distribution of the kinase in rat brain was examined. This study revealed that the concentration of the kinase varies markedly in different brain regions. It is most highly concentrated in the telencephalon where it comprises approximately 2% of total hippocampal protein, 1.3% of cortical protein and 0.7% of striatalmore » protein. It is less concentrated in lower brain regions ranging from 0.3% of hypothalamic protein to 0.1% of protein in the pons/medulla.« less

Do aggressive driving and negative emotional driving mediate the link between impulsiveness and risky driving among young Italian drivers?

PubMed

Smorti, Martina; Guarnieri, Silvia

2016-01-01

The present study examined the contribution of impulsiveness and aggressive and negative emotional driving to the prediction of traffic violations and accidents taking into account potential mediation effects. Three hundred and four young drivers completed self-report measures assessing impulsiveness, aggressive and negative emotional driving, driving violations, and accidents. Structural equation modeling was used to assess the direct and indirect effects of impulsiveness on violations and accidents among young drivers through aggressive and negative emotional driving. Impulsiveness only indirectly influenced drivers' violations on the road via both the behavioral and emotional states of the driver. On the contrary, impulsiveness was neither directly nor indirectly associated with traffic accidents. Therefore, impulsiveness modulates young drivers' behavioral and emotional states while driving, which in turn influences risky driving.

Acceptance of drinking and driving and alcohol-involved driving crashes in California.

PubMed

MacLeod, Kara E; Karriker-Jaffe, Katherine J; Ragland, David R; Satariano, William A; Kelley-Baker, Tara; Lacey, John H

2015-08-01

Alcohol-impaired driving accounts for substantial proportion of traffic-related fatalities in the U.S. Risk perceptions for drinking and driving have been associated with various measures of drinking and driving behavior. In an effort to understand how to intervene and to better understand how risk perceptions may be shaped, this study explored whether an objective environmental-level measure (proportion of alcohol-involved driving crashes in one's residential city) were related to individual-level perceptions and behavior. Using data from a 2012 cross-sectional roadside survey of 1147 weekend nighttime drivers in California, individual-level self-reported acceptance of drinking and driving and past-year drinking and driving were merged with traffic crash data using respondent ZIP codes. Population average logistic regression modeling was conducted for the odds of acceptance of drinking and driving and self-reported, past-year drinking and driving. A non-linear relationship between city-level alcohol-involved traffic crashes and individual-level acceptance of drinking and driving was found. Acceptance of drinking and driving did not mediate the relationship between the proportion of alcohol-involved traffic crashes and self-reported drinking and driving behavior. However, it was directly related to behavior among those most likely to drink outside the home. The present study surveys a particularly relevant population and is one of few drinking and driving studies to evaluate the relationship between an objective environmental-level crash risk measure and individual-level risk perceptions. In communities with both low and high proportions of alcohol-involved traffic crashes there was low acceptance of drinking and driving. This may mean that in communities with low proportions of crashes, citizens have less permissive norms around drinking and driving, whereas in communities with a high proportion of crashes, the incidence of these crashes may serve as an

Acceptance of drinking and driving and alcohol-involved driving crashes in California

PubMed Central

Karriker-Jaffe, Katherine J.; Ragland, David R.; Satariano, William A.; Kelley-Baker, Tara; Lacey, John H.

2016-01-01

Background Alcohol-impaired driving accounts for substantial proportion of traffic-related fatalities in the U.S. Risk perceptions for drinking and driving have been associated with various measures of drinking and driving behavior. In an effort to understand how to intervene and to better understand how risk perceptions may be shaped, this study explored whether an objective environmental-level measure (proportion of alcohol-involved driving crashes in one's residential city) were related to individual-level perceptions and behavior. Methods Using data from a 2012 cross-sectional roadside survey of 1,147 weekend nighttime drivers in California, individual-level self-reported acceptance of drinking and driving and past-year drinking and driving were merged with traffic crash data using respondent ZIP codes. Population average logistic regression modeling was conducted for the odds of acceptance of drinking and driving and self-reported, past-year drinking and driving. Results A non-linear relationship between city-level alcohol-involved traffic crashes and individual-level acceptance of drinking and driving was found. Acceptance of drinking and driving did not mediate the relationship between the proportion of alcohol-involved traffic crashes and self-reported drinking and driving behavior. However, it was directly related to behavior among those most likely to drink outside the home. Discussion The present study surveys a particularly relevant population and is one of few drinking and driving studies to evaluate the relationship between an objective environmental-level crash risk measure and individual-level risk perceptions. In communities with both low and high proportions of alcohol-involved traffic crashes there was low acceptance of drinking and driving. This may mean that in communities with low proportions of crashes, citizens have less permissive norms around drinking and driving, whereas in communities with a high proportion of crashes, the incidence of

Automated Driving System Architecture to Ensure Safe Delegation of Driving Authority

NASA Astrophysics Data System (ADS)

YUN, Sunkil; NISHIMURA, Hidekazu

2016-09-01

In this paper, the architecture of an automated driving system (ADS) is proposed to ensure safe delegation of driving authority between the ADS and a driver. Limitations of the ADS functions may activate delegation of driving authority to a driver. However, it leads to severe consequences in emergency situations where a driver may be drowsy or distracted. To address these issues, first, the concept model for the ADS in the situation for delegation of driving authority is described taking the driver's behaviour and state into account. Second, the behaviour / state of a driver and functional flow / state of ADS and the interactions between them are modelled to understand the context where the ADS requests to delegate the driving authority to a driver. Finally, the proposed architecture of the ADS is verified under the simulations based on the emergency braking scenarios. In the verification process using simulation, we have derived the necessary condition for safe delegation of driving authority is that the ADS should assist s driver even after delegating driving authority to a driver who has not enough capability to regain control of the driving task.

Driving reduction and cessation : transitioning to not driving.

DOT National Transportation Integrated Search

2009-09-01

This project examined the process of driving reduction and cessation from the perspective of older adults (current and former drivers) and adult children. The objectives were to identify common markers of the process of driving cessation and to gain ...

Integrating Structure to Protein-Protein Interaction Networks That Drive Metastasis to Brain and Lung in Breast Cancer

PubMed Central

Engin, H. Billur; Guney, Emre; Keskin, Ozlem; Oliva, Baldo; Gursoy, Attila

2013-01-01

Blocking specific protein interactions can lead to human diseases. Accordingly, protein interactions and the structural knowledge on interacting surfaces of proteins (interfaces) have an important role in predicting the genotype-phenotype relationship. We have built the phenotype specific sub-networks of protein-protein interactions (PPIs) involving the relevant genes responsible for lung and brain metastasis from primary tumor in breast cancer. First, we selected the PPIs most relevant to metastasis causing genes (seed genes), by using the “guilt-by-association” principle. Then, we modeled structures of the interactions whose complex forms are not available in Protein Databank (PDB). Finally, we mapped mutations to interface structures (real and modeled), in order to spot the interactions that might be manipulated by these mutations. Functional analyses performed on these sub-networks revealed the potential relationship between immune system-infectious diseases and lung metastasis progression, but this connection was not observed significantly in the brain metastasis. Besides, structural analyses showed that some PPI interfaces in both metastasis sub-networks are originating from microbial proteins, which in turn were mostly related with cell adhesion. Cell adhesion is a key mechanism in metastasis, therefore these PPIs may be involved in similar molecular pathways that are shared by infectious disease and metastasis. Finally, by mapping the mutations and amino acid variations on the interface regions of the proteins in the metastasis sub-networks we found evidence for some mutations to be involved in the mechanisms differentiating the type of the metastasis. PMID:24278371

Geological and climatic forces driving speciation in the continentally distributed trilling chorus frogs (Pseudacris).

PubMed

Lemmon, Emily Moriarty; Lemmon, Alan R; Cannatella, David C

2007-09-01

Tertiary geological events and Quaternary climatic fluctuations have been proposed as important factors of speciation in the North American flora and fauna. Few studies, however, have rigorously tested hypotheses regarding the specific factors driving divergence of taxa. Here, we test explicit speciation hypotheses by correlating geologic events with divergence times among species in the continentally distributed trilling chorus frogs (Pseudacris). In particular, we ask whether marine inundation of the Mississippi Embayment, uplift of the Appalachian Mountains, or modification of the ancient Teays-Mahomet River system contributed to speciation. To examine the plausibility of ancient rivers causing divergence, we tested whether modern river systems inhibit gene flow. Additionally, we compared the effects of Quaternary climatic factors (glaciation and aridification) on levels of genetic variation. Divergence time estimates using penalized likelihood and coalescent approaches indicate that the major lineages of chorus frogs diversified during the Tertiary, and also exclude Quaternary climate change as a factor in speciation of chorus frogs. We show the first evidence that inundation of the Mississippi Embayment contributed to speciation. We reject the hypotheses that Cenozoic uplift of the Appalachians and that diversion of the Teays-Mahomet River contributed to speciation in this clade. We find that by reducing gene flow, rivers have the potential to cause divergence of lineages. Finally, we demonstrate that populations in areas affected by Quaternary glaciation and aridification have reduced levels of genetic variation compared to those from more equable regions, suggesting recent colonization.

Improved Speed Control System for the 87,000 HP Wind Tunnel Drive

NASA Technical Reports Server (NTRS)

Becks, Edward A.; Bencic, Timothy J.; Blumenthal, Philip Z.

1995-01-01

This paper describes the design, installation, and integrated systems tests for a new drive motor speed control system which was part of a recent rehab project for the NASA Lewis 8x6 Supersonic Wind Tunnel. The tunnel drive consists of three mechanically-coupled 29,000 HP wound rotor induction motors driving an axial flow compressor. Liquid rheostats are used to vary the impedance of the rotor circuits, thus varying the speed of the drive system. The new design utilizes a distributed digital control system with a dual touch screen CRT operator console to provide alarm monitoring, logging, and trending. The liquid rheostats are driven by brushtype servomotor systems with magnetostrictive linear displacement transducers used for position feedback. The new system achieved all goals for speed variations with load, motor load balance, and control of total power.

Improved speed control system for the 87,000 HP wind tunnel drive

NASA Astrophysics Data System (ADS)

Becks, Edward A.; Bencic, Timothy J.; Blumenthal, Philip Z.

1995-01-01

This paper describes the design, installation, and integrated systems tests for a new drive motor speed control system which was part of a recent rehab project for the NASA Lewis 8x6 Supersonic Wind Tunnel. The tunnel drive consists of three mechanically-coupled 29,000 HP wound rotor induction motors driving an axial flow compressor. Liquid rheostats are used to vary the impedance of the rotor circuits, thus varying the speed of the drive system. The new design utilizes a distributed digital control system with a dual touch screen CRT operator console to provide alarm monitoring, logging, and trending. The liquid rheostats are driven by brushtype servomotor systems with magnetostrictive linear displacement transducers used for position feedback. The new system achieved all goals for speed variations with load, motor load balance, and control of total power.

Direct TFIIA-TFIID Protein Contacts Drive Budding Yeast Ribosomal Protein Gene Transcription*

PubMed Central

Layer, Justin H.; Weil, P. Anthony

2013-01-01

We have previously shown that yeast TFIID provides coactivator function on the promoters of ribosomal protein-encoding genes (RPGs) by making direct contact with the transactivator repressor activator protein 1 (Rap1). Further, our structural studies of assemblies generated with purified Rap1, TFIID, and TFIIA on RPG enhancer-promoter DNA indicate that Rap1-TFIID interaction induces dramatic conformational rearrangements of enhancer-promoter DNA and TFIID-bound TFIIA. These data indicate a previously unknown yet critical role for yeast TFIIA in the integration of activator-TFIID contacts with promoter conformation and downstream preinitiation complex formation and/or function. Here we describe the use of systematic mutagenesis to define how specific TFIIA contacts contribute to these processes. We have verified that TFIIA is required for RPG transcription in vivo and in vitro, consistent with the existence of a critical Rap1-TFIIA-TFIID interaction network. We also identified essential points of contact for TFIIA and Rap1 within the Rap1 binding domain of the Taf4 subunit of TFIID. These data suggest a mechanism for how interactions between TFIID, TFIIA, and Rap1 contribute to the high rate of transcription initiation seen on RPGs in vivo. PMID:23814059

Exposure to Movie Reckless Driving in Early Adolescence Predicts Reckless, but Not Inattentive Driving.

PubMed

Kostermans, Evelien; Stoolmiller, Mike; de Leeuw, Rebecca N H; Engels, Rutger C M E; Sargent, James D

2014-01-01

We examine the association between exposure to depictions of reckless driving in movies and unsafe driving, modeling inattentive and reckless driving as separate outcomes. Data were obtained by telephone from 1,630 US adolescents aged 10 to 14 years at baseline who were drivers at a survey 6 years later. Exposure to movie reckless driving was measured based on movies seen from a randomly selected list of 50 movie titles that had been content coded for reckless driving among characters. Associations were tested with inattentive and reckless driving behaviors in the subsequent survey-controlling for baseline age, sex, socioeconomic status, parental education, school performance, extracurricular activities, daily television and video/computer game exposure, number of movies watched per week, self-regulation and sensation seeking. Exposure to movie reckless driving was common, with approximately 10% of movie characters having driven recklessly. Confirmatory factor analysis revealed a significant distinction between items tapping reckless and inattentive driving at the 6th wave. Age and exposure to movie reckless driving at baseline were directly associated with wave-6 reckless (but not inattentive) driving. Additionally, growth in sensation seeking mediated a prospective relation between the total number of movies watched per week at baseline and reckless driving, independent of exposure to movie reckless driving. Males and high sensation seekers reported lower seatbelt usage and more reckless driving, whereas lower self-regulation predicted inattentive driving. In this study, exposure to movie reckless driving during early adolescence predicted adolescents' reckless driving, suggesting a direct modeling effect. Other aspects of movies were also associated with reckless driving, with that association mediated through growth in sensation seeking. Predictors of reckless driving were different from predictors of inattentive driving, with lower self-regulation associated

Exposure to Movie Reckless Driving in Early Adolescence Predicts Reckless, but Not Inattentive Driving

PubMed Central

Kostermans, Evelien; Stoolmiller, Mike; de Leeuw, Rebecca N. H.; Engels, Rutger C. M. E.; Sargent, James D.

2014-01-01

Objective We examine the association between exposure to depictions of reckless driving in movies and unsafe driving, modeling inattentive and reckless driving as separate outcomes. Methods Data were obtained by telephone from 1,630 US adolescents aged 10 to 14 years at baseline who were drivers at a survey 6 years later. Exposure to movie reckless driving was measured based on movies seen from a randomly selected list of 50 movie titles that had been content coded for reckless driving among characters. Associations were tested with inattentive and reckless driving behaviors in the subsequent survey–controlling for baseline age, sex, socioeconomic status, parental education, school performance, extracurricular activities, daily television and video/computer game exposure, number of movies watched per week, self-regulation and sensation seeking. Results Exposure to movie reckless driving was common, with approximately 10% of movie characters having driven recklessly. Confirmatory factor analysis revealed a significant distinction between items tapping reckless and inattentive driving at the 6th wave. Age and exposure to movie reckless driving at baseline were directly associated with wave-6 reckless (but not inattentive) driving. Additionally, growth in sensation seeking mediated a prospective relation between the total number of movies watched per week at baseline and reckless driving, independent of exposure to movie reckless driving. Males and high sensation seekers reported lower seatbelt usage and more reckless driving, whereas lower self-regulation predicted inattentive driving. Discussion In this study, exposure to movie reckless driving during early adolescence predicted adolescents’ reckless driving, suggesting a direct modeling effect. Other aspects of movies were also associated with reckless driving, with that association mediated through growth in sensation seeking. Predictors of reckless driving were different from predictors of inattentive driving

Gear bearing drive

NASA Technical Reports Server (NTRS)

Mavroidis, Constantinos (Inventor); Vranish, John M. (Inventor); Weinberg, Brian (Inventor)

2011-01-01

A gear bearing drive provides a compact mechanism that operates as an actuator providing torque and as a joint providing support. The drive includes a gear arrangement integrating an external rotor DC motor within a sun gear. Locking surfaces maintain the components of the drive in alignment and provide support for axial loads and moments. The gear bearing drive has a variety of applications, including as a joint in robotic arms and prosthetic limbs.

The spatial distribution of fixed mutations within genes coding for proteins

NASA Technical Reports Server (NTRS)

Holmquist, R.; Goodman, M.; Conroy, T.; Czelusniak, J.

1983-01-01

An examination has been conducted of the extensive amino acid sequence data now available for five protein families - the alpha crystallin A chain, myoglobin, alpha and beta hemoglobin, and the cytochromes c - with the goal of estimating the true spatial distribution of base substitutions within genes that code for proteins. In every case the commonly used Poisson density failed to even approximate the experimental pattern of base substitution. For the 87 species of beta hemoglobin examined, for example, the probability that the observed results were from a Poisson process was the minuscule 10 to the -44th. Analogous results were obtained for the other functional families. All the data were reasonably, but not perfectly, described by the negative binomial density. In particular, most of the data were described by one of the very simple limiting forms of this density, the geometric density. The implications of this for evolutionary inference are discussed. It is evident that most estimates of total base substitutions between genes are badly in need of revision.

Hostility, driving anger, and dangerous driving: the emerging role of hemispheric preference.

PubMed

Gidron, Yori; Gaygısız, Esma; Lajunen, Timo

2014-12-01

Various studies have implicated psychosocial variables (e.g., hostility) in risk of dangerous driving and traffic accidents. However, whether these variables are related to more basic neurobiological factors, and whether such associations have implications for the modification of psychosocial risk factors in the context of driving, have not been examined in depth. This study examined the relationship between hemispheric preference (HP), hostility and self-reported dangerous driving, and the ability to affect driving anger via hemisphere activating cognitive exercises (HACE). In Study 1, 254 Turkish students completed questionnaires of hostility, HP and driving behavior. In Study 2, we conducted a "proof of concept" experimental study, and tested effects of left, right and neutral HACE on driving anger, by exposing N=650 Turkish students to written scenarios including either logical (left hemisphere), visuo-spatial (right hemisphere) or "mild doses" of both types of contents (control). In Study 1, left-HP was associated with higher hostility and with more dangerous driving, and hostility mediated the relationship between L-HP and reported driving behavior. In Study 2, only right-HACE led to immediate significant reductions in self-reported driving anger. Left-HP is related to hostility and to dangerous driving, and it may be possible to partly reduce driving anger by right-HACE. Future studies must replicate these findings with objective measures, more enduring interventions and longer follow-ups. Copyright © 2014. Published by Elsevier Ltd.

Driving performance and driver discomfort in an elevated and standard driving position during a driving simulation.

PubMed

Smith, Jordan; Mansfield, Neil; Gyi, Diane; Pagett, Mark; Bateman, Bob

2015-07-01

The primary purposes of a vehicle driver's seat, is to allow them to complete the driving task comfortably and safely. Within each class of vehicle (e.g. passenger, commercial, industrial, agricultural), there is an expected driving position to which a vehicle cabin is designed. This paper reports a study that compares two driving positions, in relation to Light Commercial Vehicles (LCVs), in terms of driver performance and driver discomfort. In the 'elevated' driving position, the seat is higher than usually used in road vehicles; this is compared to a standard driving position replicating the layout for a commercially available vehicle. It is shown that for a sample of 12 drivers, the elevated position did not, in general, show more discomfort than the standard position over a 60 min driving simulation, although discomfort increased with duration. There were no adverse effects shown for emergency stop reaction time or for driver headway for the elevated posture compared to the standard posture. The only body part that showed greater discomfort for the elevated posture compared to the standard posture was the right ankle. A second experiment confirmed that for 12 subjects, a higher pedal stiffness eliminated the ankle discomfort problem. Copyright © 2015 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Parental perceptions of teen driving: Restrictions, worry and influence☆

PubMed Central

Jewett, Amy; Shults, Ruth A.; Bhat, Geeta

2016-01-01

Introduction Parents play a critical role in preventing crashes among teens. Research of parental perceptions and concerns regarding teen driving safety is limited. We examined results from the 2013 Summer ConsumerStyles survey that queried parents about restrictions placed on their teen drivers, their perceived level of “worry” about their teen driver’s safety, and influence of parental restrictions regarding their teen’s driving. Methods We produced frequency distributions for the number of restrictions imposed, parental “worry,” and influence of rules regarding their teen’s driving, reported by teen’s driving license status (learning to drive or obtained a driver’s license). Response categories were dichotomized because of small cell sizes, and we ran separate log-linear regression models to explore whether imposing all four restrictions on teen drivers was associated with either worry intensity (“a lot” versus “somewhat, not very much or not at all”) or perceived influence of parental rules (“a lot” versus “somewhat, not very much or not at all”). Results Among the 456 parent respondents, 80% reported having restrictions for their teen driver regarding use of safety belts, drinking and driving, cell phones, and text messaging while driving. However, among the 188 parents of licensed teens, only 9% reported having a written parent-teen driving agreement, either currently or in the past. Worrying “a lot” was reported less frequently by parents of newly licensed teens (36%) compared with parents of learning teens (61%). Conclusions and Practical Applications Parents report having rules and restrictions for their teen drivers, but only a small percentage formalize the rules and restrictions in a written parent-teen driving agreement. Parents worry less about their teen driver’s safety during the newly licensed phase, when crash risk is high as compared to the learning phase. Further research is needed into how to effectively

Distribution of cold adaptation proteins in microbial mats in Lake Joyce, Antarctica: Analysis of metagenomic data by using two bioinformatics tools.

PubMed

Koo, Hyunmin; Hakim, Joseph A; Fisher, Phillip R E; Grueneberg, Alexander; Andersen, Dale T; Bej, Asim K

2016-01-01

In this study, we report the distribution and abundance of cold-adaptation proteins in microbial mat communities in the perennially ice-covered Lake Joyce, located in the McMurdo Dry Valleys, Antarctica. We have used MG-RAST and R code bioinformatics tools on Illumina HiSeq2000 shotgun metagenomic data and compared the filtering efficacy of these two methods on cold-adaptation proteins. Overall, the abundance of cold-shock DEAD-box protein A (CSDA), antifreeze proteins (AFPs), fatty acid desaturase (FAD), trehalose synthase (TS), and cold-shock family of proteins (CSPs) were present in all mat samples at high, moderate, or low levels, whereas the ice nucleation protein (INP) was present only in the ice and bulbous mat samples at insignificant levels. Considering the near homogeneous temperature profile of Lake Joyce (0.08-0.29 °C), the distribution and abundance of these proteins across various mat samples predictively correlated with known functional attributes necessary for microbial communities to thrive in this ecosystem. The comparison of the MG-RAST and the R code methods showed dissimilar occurrences of the cold-adaptation protein sequences, though with insignificant ANOSIM (R = 0.357; p-value = 0.012), ADONIS (R(2) = 0.274; p-value = 0.03) and STAMP (p-values = 0.521-0.984) statistical analyses. Furthermore, filtering targeted sequences using the R code accounted for taxonomic groups by avoiding sequence redundancies, whereas the MG-RAST provided total counts resulting in a higher sequence output. The results from this study revealed for the first time the distribution of cold-adaptation proteins in six different types of microbial mats in Lake Joyce, while suggesting a simpler and more manageable user-defined method of R code, as compared to a web-based MG-RAST pipeline.

Distribution of surfactant protein A in rat lung.

PubMed

Doyle, I R; Barr, H A; Nicholas, T E

1994-10-01

Although surfactant protein A (SP-A) is an integral component of alveolar surfactant, its relative abundance in lamellar bodies, regarded as the intracellular storage organelles for surfactant, remains contentious. We have previously shown that lamellar bodies, isolated from rat lung by upward flotation on a sucrose gradient, can be subfractionated into classic-appearing lamellar bodies (Lb-A) and a vesicular fraction (Lb-B), which we have speculated may be a second release form of surfactant. In the present study, we have used two-dimensional protein electrophoresis and immunochemical analysis to clarify the origin and the composition of these two subcellular fractions. In addition, we have examined the hypothesis that the secretion of SP-A and surfactant phospholipids occurs by independent pathways by examining the distribution of SP-A, total protein, and disaturated phospholipids (DSP) in the tubular myelin-rich (Alv-1) and tubular myelin-poor (Alv-2) fractions separated from lavaged material and in Lb-A and Lb-B isolated from both lung homogenate and purified alveolar type II cells. Our findings indicate that Lb-B is derived from type II cells, although they do not indicate whether it is a secretory form of surfactant, a reuptake vesicle, or a mixture of both. We found that the lung has a large tissue pool of immunoreactive SP-A. The %SP-A/DSP of total lamellar bodies isolated from type II cells was 0.96 +/- 0.1 (mean +/- SE), intermediate between that in Lb-A (1.67 +/- 0.13) and in Lb-B (0.65 +/- 0.04). In contrast, the %SP-A/DSP was 11.16 +/- 0.84 in whole lung homogenate and 13.14 +/- 1.71 in whole type II cells. In the alveolar compartment, the %SP-A/DSP was 17.38 +/- 3.40 in Alv-1, 6.34 +/- 0.31 in Alv-2, and 10.49 +/- 1.43 in macrophages, values an order of magnitude greater than found with the lamellar bodies. Our results indicate that only a relatively small portion of alveolar SP-A is derived from lamellar bodies, and we suggest that secretion of SP

Drugged Driving

MedlinePlus

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter ... in the past year. Middle Figure: Driving after marijuana use is more common than driving after alcohol ...

Using Local States To Drive the Sampling of Global Conformations in Proteins

PubMed Central

2016-01-01

Conformational changes associated with protein function often occur beyond the time scale currently accessible to unbiased molecular dynamics (MD) simulations, so that different approaches have been developed to accelerate their sampling. Here we investigate how the knowledge of backbone conformations preferentially adopted by protein fragments, as contained in precalculated libraries known as structural alphabets (SA), can be used to explore the landscape of protein conformations in MD simulations. We find that (a) enhancing the sampling of native local states in both metadynamics and steered MD simulations allows the recovery of global folded states in small proteins; (b) folded states can still be recovered when the amount of information on the native local states is reduced by using a low-resolution version of the SA, where states are clustered into macrostates; and (c) sequences of SA states derived from collections of structural motifs can be used to sample alternative conformations of preselected protein regions. The present findings have potential impact on several applications, ranging from protein model refinement to protein folding and design. PMID:26808351

Using Local States To Drive the Sampling of Global Conformations in Proteins.

PubMed

Pandini, Alessandro; Fornili, Arianna

2016-03-08

Conformational changes associated with protein function often occur beyond the time scale currently accessible to unbiased molecular dynamics (MD) simulations, so that different approaches have been developed to accelerate their sampling. Here we investigate how the knowledge of backbone conformations preferentially adopted by protein fragments, as contained in precalculated libraries known as structural alphabets (SA), can be used to explore the landscape of protein conformations in MD simulations. We find that (a) enhancing the sampling of native local states in both metadynamics and steered MD simulations allows the recovery of global folded states in small proteins; (b) folded states can still be recovered when the amount of information on the native local states is reduced by using a low-resolution version of the SA, where states are clustered into macrostates; and (c) sequences of SA states derived from collections of structural motifs can be used to sample alternative conformations of preselected protein regions. The present findings have potential impact on several applications, ranging from protein model refinement to protein folding and design.

Method for controlling protein crystallization

NASA Technical Reports Server (NTRS)

Noever, David A. (Inventor)

1993-01-01

A method and apparatus for controlling the crystallization of protein by solvent evaporation including placing a drop of protein solution between and in contact with a pair of parallel plates and driving one of the plates toward and away from the other plate in a controlled manner to adjust the spacing between the plates is presented. The drop of solution forms a liquid cylinder having a height dependent upon the plate spacing thereby effecting the surface area available for solvent evaporation. When the spacing is close, evaporation is slow. Evaporation is increased by increasing the spacing between the plates until the breaking point of the liquid cylinder. One plate is mounted upon a fixed post while the other plate is carried by a receptacle movable relative to the post and driven by a belt driven screw drive. The temperature and humidity of the drop of protein solution are controlled by sealing the drop within the receptacle and mounting a heater and dessicant within the receptacle.

Assessment of driving-related performance in chronic whiplash using an advanced driving simulator.

PubMed

Takasaki, Hiroshi; Treleaven, Julia; Johnston, Venerina; Rakotonirainy, Andry; Haines, Andrew; Jull, Gwendolen

2013-11-01

Driving is often nominated as problematic by individuals with chronic whiplash associated disorders (WAD), yet driving-related performance has not been evaluated objectively. The purpose of this study was to test driving-related performance in persons with chronic WAD against healthy controls of similar age, gender and driving experience to determine if driving-related performance in the WAD group was sufficiently impaired to recommend fitness to drive assessment. Driving-related performance was assessed using an advanced driving simulator during three driving scenarios; freeway, residential and a central business district (CBD). Total driving duration was approximately 15min. Five driving tasks which could cause a collision (critical events) were included in the scenarios. In addition, the effect of divided attention (identify red dots projected onto side or rear view mirrors) was assessed three times in each scenario. Driving performance was measured using the simulator performance index (SPI) which is calculated from 12 measures. z-Scores for all SPI measures were calculated for each WAD subject based on mean values of the control subjects. The z-scores were then averaged for the WAD group. A z-score of ≤-2 indicated a driving failing grade in the simulator. The number of collisions over the five critical events was compared between the WAD and control groups as was reaction time and missed response ratio in identifying the red dots. Seventeen WAD and 26 control subjects commenced the driving assessment. Demographic data were comparable between the groups. All subjects completed the freeway scenario but four withdrew during the residential and eight during the CBD scenario because of motion sickness. All scenarios were completed by 14 WAD and 17 control subjects. Mean z-scores for the SPI over the three scenarios was statistically lower in the WAD group (-0.3±0.3; P<0.05) but the score was not below the cut-off point for safe driving. There were no

The effects of cognitively demanding dual-task driving condition on elderly people's driving performance; Real driving monitoring.

PubMed

Ebnali, Mahdi; Ahmadnezhad, Pedram; Shateri, Alireza; Mazloumi, Adel; Ebnali Heidari, Majid; Nazeri, Ahmad Reza

2016-09-01

Using in-vehicle audio technologies such as audio systems and voice messages is regarded as a common secondary task. Such tasks, known as the sources of non-visual distraction, affect the driving performance. Given the elderly drivers' cognitive limitations, driving can be even more challenging to drivers. The current study examined how listening to economic news, as a cognitively demanding secondary task, affects elderly subjects' driving performance and whether their comprehension accuracy is associated with these effects. Participants of the study (N=22) drove in a real condition with and without listening to economic news. Measurements included driving performance (speed control, forward crash risk, and lateral lane position) and task performance (comprehension accuracy). The mean driving speed, duration of driving in unsafe zones and numbers of overtaking decreased significantly when drivers were engaged in the dual-task condition. Moreover, the cognitive secondary task led to a higher speed variability. Our results demonstrate that there was not a significant relationship between the lane changes and the activity of listening to economic news. However, a meaningful difference was observed between general comprehension and deep comprehension on the one hand and driving performance on the other. Another aspect of our study concerning the drivers' ages and their comprehension revealed a significant relationship between age above 75 and comprehension level. Drivers aging 75 and older showed a lower level of deep comprehension. Our study demonstrates that elderly drivers compensated driving performance with safety margin adoption while they were cognitively engaged. In this condition, however, maintaining speed proved more demanding for drivers aging 75 and older. Copyright © 2016 Elsevier Ltd. All rights reserved.

Driving and dementia

PubMed Central

Lee, Linda; Molnar, Frank

2017-01-01

Abstract Objective To provide primary care physicians with an approach to driving safety concerns when older persons present with memory difficulties. Sources of information The approach is based on an accredited memory clinic training program developed by the Centre for Family Medicine Primary Care Collaborative Memory Clinic. Main message One of the most challenging aspects of dementia care is the assessment of driving safety. Drivers with dementia are at higher risk of motor vehicle collisions, yet many drivers with mild dementia might be safely able to continue driving for several years. Because safe driving is dependent on multiple cognitive and functional skills, clinicians should carefully consider many factors when determining if cognitive concerns affect driving safety. Specific findings on corroborated history and office-based cognitive testing might aid in the physician’s decisions to refer for comprehensive on-road driving evaluation and whether to notify transportation authorities in accordance with provincial reporting requirements. Sensitive communication and a person-centred approach are essential. Conclusion Primary care physicians must consider many factors when determining if cognitive concerns might affect driving safety in older drivers. PMID:28115437

Driving Cell Seeding Using Vibration Induced Surface Waves

NASA Astrophysics Data System (ADS)

Li, Haiyan; Friend, James; Yeo, Leslie

2007-11-01

The ability to load cells into scaffold matrices is an important step in in-vitro cell culturing. Efficient and rapid cell seeding is however difficult and has traditionally been carried out using a static method by allowing gravity to drive the perfusion of the cell suspension into the porous scaffold. Nevertheless, due to the large capillary pressures associated with the small scaffold pore dimensions, the static cell seeding method is both slow and inefficient; the majority of cells are distributed close to the surface of the scaffold due to the inability of the fluid to penetrate deep into the scaffold. By driving the liquid into the scaffold using small amplitude surface vibrations on a piezoelectric substrate, we demonstrate that the cells can be infused much quicker (approximately 10 seconds) than if allowed to perfuse by gravity alone, which requires seeding times in excess of 30 minutes. Greater penetration of the fluid and hence the cells into the scaffold is also achieved with the vibration forcing, thus giving rise to a more uniform cell distribution within the scaffold. Moreover, we have verified that 80% of the yeast cells seeded by the surface waves remained viable.

Distribution of keratin and associated proteins in the epidermis of monotreme, marsupial, and placental mammals.

PubMed

Alibardi, Lorenzo; Maderson, Paul F A

2003-10-01

The expression of acidic and basic keratins, and of some keratinization marker proteins such as filaggrin, loricrin, involucrin, and trichohyalin, is known for the epidermis of only a few eutherian species. Using light and high-resolution immunocytochemistry, the presence of these proteins has been studied in two monotreme and five marsupial species and compared to that in eutherians. In both monotreme and marsupial epidermis lamellar bodies occur in the upper spinosus and granular layers. Development of the granular layer varies between species and regionally within species. There is great interspecific variation in the size (0.1-3.0 microm) of keratohyalin granules (KHGs) associated with production of orthokeratotic corneous tissues. Those skin regions lacking hairs (platypus web), or showing reduced pelage density (wombat) have, respectively, minute or indiscernible KHGs, associated with patchy, or total, parakeratosis. Ultrastructural analysis shows that monotreme and marsupial KHGs comprise irregular coarse filaments of 25-40 nm that contact keratin filaments. Except for parakeratotic tissues of platypus web, distribution of acidic and basic proteins in monotreme and marsupial epidermis as revealed by anti-keratin antibodies AE1, AE2, and AE3 resembles that of eutherian epidermis. Antibodies against human or rat filaggrins have little or no cross-reactivity with epidermal proteins of other mammals: only sparse areas of wombat and rabbit epidermis show a weak immunofluorescence in transitional cells and in the deepest corneous tissues. Of the available, eutherian-derived antibodies, that against involucrin shows no cross-reactivity with any monotreme and marsupial epidermal tissues and that against trichohyalin cross-reacts only with cells in the inner root sheath and medulla of hairs. These results suggest that if involucrin and trichohyalin are present throughout noneutherian epidermis, they may have species-specific molecular structures. By contrast

Family communication patterns and teen drivers' attitudes toward driving safety.

PubMed

Yang, Jingzhen; Campo, Shelly; Ramirez, Marizen; Krapfl, Julia Richards; Cheng, Gang; Peek-Asa, Corinne

2013-01-01

Family communication patterns (FCPs) play an important role in reducing the risk-taking behaviors of teens, such as substance use and safer sex. However, little is known about the relationship between family communication and teen driving safety. We analyzed the baseline data from a randomized trial that included 163 parent-teen dyads, with teens who would be receiving their intermediate driver's license within 3 months. FCPs were divided into four types-pluralistic, protective, consensual, and laissez-faire-and were correlated with the frequency of parent-teen discussions and teens' driving safety attitudes. The ratings on four types of FCPs were distributed quite evenly among teens and parents. Parents and teens agreed on their FCP ratings (p = .64). In families with communication patterns that were laissez-faire, protective, and pluralistic, parents talked to their teens less about safe driving than did parents in families with a consensual communication pattern (p < .01). Moreover, the frequency of parent-teen communication about safe driving was positively associated with teen attitudes toward safe driving (adjusted β = 0.35, p = .03). Health care providers need to encourage parents, particularly those with non-consensual FCPs, to increase frequency of parent-teen interactions. Copyright © 2013 National Association of Pediatric Nurse Practitioners. Published by Mosby, Inc. All rights reserved.

Driving Task: How Older Drivers' On-Road Driving Performance Relates to Abilities, Perceptions, and Restrictions.

PubMed

Koppel, Sjaan; Charlton, Judith L; Langford, Jim; Di Stefano, Marilyn; MacDonald, Wendy; Vlahodimitrakou, Zafiroula; Mazer, Barbara L; Gelinas, Isabelle; Vrkljan, Brenda; Eliasz, Kinga; Myers, Anita; Tuokko, Holly A; Marshall, Shawn C

2016-06-01

This study examined a cohort of 227 older drivers and investigated the relationship between performance on the electronic Driver Observation Schedule (eDOS) driving task and: (1) driver characteristics; (2) functional abilities; (3) perceptions of driving comfort and abilities; and (4) self-reported driving restrictions. Participants (male: 70%; age: M = 81.53 years, SD = 3.37 years) completed a series of functional ability measures and scales on perceived driving comfort, abilities, and driving restrictions from the Year 2 Candrive/Ozcandrive assessment protocol, along with an eDOS driving task. Observations of participants' driving behaviours during the driving task were recorded for intersection negotiation, lane-changing, merging, low-speed maneuvers, and maneuver-free driving. eDOS driving task scores were high (M = 94.74; SD = 5.70) and significantly related to participants' perceived driving abilities, reported frequency of driving in challenging situations, and number of driving restrictions. Future analyses will explore potential changes in driving task scores over time.

Hendra virus fusion protein transmembrane domain contributes to pre-fusion protein stability.

PubMed

Webb, Stacy; Nagy, Tamas; Moseley, Hunter; Fried, Michael; Dutch, Rebecca

2017-04-07

Enveloped viruses utilize fusion (F) proteins studding the surface of the virus to facilitate membrane fusion with a target cell membrane. Fusion of the viral envelope with a cellular membrane is required for release of viral genomic material, so the virus can ultimately reproduce and spread. To drive fusion, the F protein undergoes an irreversible conformational change, transitioning from a metastable pre-fusion conformation to a more thermodynamically stable post-fusion structure. Understanding the elements that control stability of the pre-fusion state and triggering to the post-fusion conformation is important for understanding F protein function. Mutations in F protein transmembrane (TM) domains implicated the TM domain in the fusion process, but the structural and molecular details in fusion remain unclear. Previously, analytical ultracentrifugation was utilized to demonstrate that isolated TM domains of Hendra virus F protein associate in a monomer-trimer equilibrium (Smith, E. C., Smith, S. E., Carter, J. R., Webb, S. R., Gibson, K. M., Hellman, L. M., Fried, M. G., and Dutch, R. E. (2013) J. Biol. Chem. 288, 35726-35735). To determine factors driving this association, 140 paramyxovirus F protein TM domain sequences were analyzed. A heptad repeat of β-branched residues was found, and analysis of the Hendra virus F TM domain revealed a heptad repeat leucine-isoleucine zipper motif (LIZ). Replacement of the LIZ with alanine resulted in dramatically reduced TM-TM association. Mutation of the LIZ in the whole protein resulted in decreased protein stability, including pre-fusion conformation stability. Together, our data suggest that the heptad repeat LIZ contributed to TM-TM association and is important for F protein function and pre-fusion stability. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

The DEG/ENaC cation channel protein UNC-8 drives activity-dependent synapse removal in remodeling GABAergic neurons

PubMed Central

Miller-Fleming, Tyne W; Petersen, Sarah C; Manning, Laura; Matthewman, Cristina; Gornet, Megan; Beers, Allison; Hori, Sayaka; Mitani, Shohei; Bianchi, Laura; Richmond, Janet; Miller, David M

2016-01-01

Genetic programming and neural activity drive synaptic remodeling in developing neural circuits, but the molecular components that link these pathways are poorly understood. Here we show that the C. elegans Degenerin/Epithelial Sodium Channel (DEG/ENaC) protein, UNC-8, is transcriptionally controlled to function as a trigger in an activity-dependent mechanism that removes synapses in remodeling GABAergic neurons. UNC-8 cation channel activity promotes disassembly of presynaptic domains in DD type GABA neurons, but not in VD class GABA neurons where unc-8 expression is blocked by the COUP/TF transcription factor, UNC-55. We propose that the depolarizing effect of UNC-8-dependent sodium import elevates intracellular calcium in a positive feedback loop involving the voltage-gated calcium channel UNC-2 and the calcium-activated phosphatase TAX-6/calcineurin to initiate a caspase-dependent mechanism that disassembles the presynaptic apparatus. Thus, UNC-8 serves as a link between genetic and activity-dependent pathways that function together to promote the elimination of GABA synapses in remodeling neurons. DOI: http://dx.doi.org/10.7554/eLife.14599.001 PMID:27403890

Zea mays Taxilin Protein Negatively Regulates Opaque-2 Transcriptional Activity by Causing a Change in Its Sub-Cellular Distribution

PubMed Central

Zhang, Nan; Qiao, Zhenyi; Liang, Zheng; Mei, Bing; Xu, Zhengkai; Song, Rentao

2012-01-01

Zea mays (maize) Opaque-2 (ZmO2) protein is an important bZIP transcription factor that regulates the expression of major storage proteins (22-kD zeins) and other important genes during maize seed development. ZmO2 is subject to functional regulation through protein-protein interactions. To unveil the potential regulatory network associated with ZmO2, a protein-protein interaction study was carried out using the truncated version of ZmO2 (O2-2) as bait in a yeast two-hybrid screen with a maize seed cDNA library. A protein with homology to Taxilin was found to have stable interaction with ZmO2 in yeast and was designated as ZmTaxilin. Sequence analysis indicated that ZmTaxilin has a long coiled-coil domain containing three conserved zipper motifs. Each of the three zipper motifs is individually able to interact with ZmO2 in yeast. A GST pull-down assay demonstrated the interaction between GST-fused ZmTaxilin and ZmO2 extracted from developing maize seeds. Using onion epidermal cells as in vivo assay system, we found that ZmTaxilin could change the sub-cellular distribution of ZmO2. We also demonstrated that this change significantly repressed the transcriptional activity of ZmO2 on the 22-kD zein promoter. Our study suggests that a Taxilin-mediated change in sub-cellular distribution of ZmO2 may have important functional consequences for ZmO2 activity. PMID:22937104

Periodic and stochastic thermal modulation of protein folding kinetics.

PubMed

Platkov, Max; Gruebele, Martin

2014-07-21

Chemical reactions are usually observed either by relaxation of a bulk sample after applying a sudden external perturbation, or by intrinsic fluctuations of a few molecules. Here we show that the two ideas can be combined to measure protein folding kinetics, either by periodic thermal modulation, or by creating artificial thermal noise that greatly exceeds natural thermal fluctuations. We study the folding reaction of the enzyme phosphoglycerate kinase driven by periodic temperature waveforms. As the temperature waveform unfolds and refolds the protein, its fluorescence color changes due to FRET (Förster resonant Energy Transfer) of two donor/acceptor fluorophores labeling the protein. We adapt a simple model of periodically driven kinetics that nicely fits the data at all temperatures and driving frequencies: The phase shifts of the periodic donor and acceptor fluorescence signals as a function of driving frequency reveal reaction rates. We also drive the reaction with stochastic temperature waveforms that produce thermal fluctuations much greater than natural fluctuations in the bulk. Such artificial thermal noise allows the recovery of weak underlying signals due to protein folding kinetics. This opens up the possibility for future detection of a stochastic resonance for protein folding subject to noise with controllable amplitude.

Chinese carless young drivers' self-reported driving behavior and simulated driving performance.

PubMed

Zhang, Qian; Jiang, Zuhua; Zheng, Dongpeng; Man, Dong; Xu, Xunnan

2013-01-01

Carless young drivers refers to those drivers aged between 18 and 25 years who have a driver's license but seldom have opportunities to practice their driving skills because they do not have their own cars. Due to China's lower private car ownership, many young drivers become carless young drivers after licensure, and the safety issue associated with them has raised great concern in China. This study aims to provide initial insight into the self-reported driving behaviors and simulated driving performance of Chinese carless young drivers. Thirty-three carless young drivers and 32 young drivers with their own cars (as a comparison group) participated in this study. A modified Driver Behavior Questionnaire (DBQ) with a 4-factor structure (errors, violations, attention lapses, and memory lapses) was used to study carless young drivers' self-reported driving behaviors. A simulated driving experiment using a low-cost, fixed-base driving simulator was conducted to measure their simulated driving performance (errors, violations, attention lapses, driving maintenance, reaction time, and accidents). Self-reported DBQ outcomes showed that carless young drivers reported similar errors, more attention lapses, fewer memory lapses, and significantly fewer violation behaviors relative to young drivers with their own cars, whereas simulated driving results revealed that they committed significantly more errors, attention lapses, and violation behaviors than the comparison group. Carless young drivers had a lower ability to maintain the stability of speed and lane position, drove more cautiously approaching and passing through red traffic lights, and committed more accidents during simulated driving. A tendency to speed was not found among carless young drivers; their average speed and speeding frequency were all much lower than that of the comparison group. Lifetime mileage was the only significant predictor of carless young drivers' self-reported violations, simulated violations

Reconfigurable Drive Current System

NASA Technical Reports Server (NTRS)

Alhorn, Dean C. (Inventor); Dutton, Kenneth R. (Inventor); Howard, David E. (Inventor); Smith, Dennis A. (Inventor)

2017-01-01

A reconfigurable drive current system includes drive stages, each of which includes a high-side transistor and a low-side transistor in a totem pole configuration. A current monitor is coupled to an output of each drive stage. Input channels are provided to receive input signals. A processor is coupled to the input channels and to each current monitor for generating at least one drive signal using at least one of the input signals and current measured by at least one of the current monitors. A pulse width modulation generator is coupled to the processor and each drive stage for varying the drive signals as a function of time prior to being supplied to at least one of the drive stages.

Age-related carbonylation of fibrocartilage structural proteins drives tissue degenerative modification.

PubMed

Scharf, Brian; Clement, Cristina C; Yodmuang, Supansa; Urbanska, Aleksandra M; Suadicani, Sylvia O; Aphkhazava, David; Thi, Mia M; Perino, Giorgio; Hardin, John A; Cobelli, Neil; Vunjak-Novakovic, Gordana; Santambrogio, Laura

2013-07-25

Aging-related oxidative stress has been linked to degenerative modifications in different organs and tissues. Using redox proteomic analysis and illustrative tandem mass spectrometry mapping, we demonstrate oxidative posttranslational modifications in structural proteins of intervertebral discs (IVDs) isolated from aging mice. Increased protein carbonylation was associated with protein fragmentation and aggregation. Complementing these findings, a significant loss of elasticity and increased stiffness was measured in fibrocartilage from aging mice. Studies using circular dichroism and intrinsic tryptophan fluorescence revealed a significant loss of secondary and tertiary structures of purified collagens following oxidation. Collagen unfolding and oxidation promoted both nonenzymatic and enzymatic degradation. Importantly, induction of oxidative modification in healthy fibrocartilage recapitulated the biochemical and biophysical modifications observed in the aging IVD. Together, these results suggest that protein carbonylation, glycation, and lipoxidation could be early events in promoting IVD degenerative changes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Molecular determinants of Guanylate Cyclase Activating Protein subcellular distribution in photoreceptor cells of the retina.

PubMed

López-Begines, Santiago; Plana-Bonamaisó, Anna; Méndez, Ana

2018-02-13

Retinal guanylate cyclase (RetGC) and guanylate cyclase activating proteins (GCAPs) play an important role during the light response in photoreceptor cells. Mutations in these proteins are linked to distinct forms of blindness. RetGC and GCAPs exert their role at the ciliary outer segment where phototransduction takes place. We investigated the mechanisms governing GCAP1 and GCAP2 distribution to rod outer segments by expressing selected GCAP1 and GCAP2 mutants as transient transgenes in the rods of GCAP1/2 double knockout mice. We show that precluding GCAP1 direct binding to RetGC (K23D/GCAP1) prevented its distribution to rod outer segments, while preventing GCAP1 activation of RetGC post-binding (W94A/GCAP1) did not. We infer that GCAP1 translocation to the outer segment strongly depends on GCAP1 binding affinity for RetGC, which points to GCAP1 requirement to bind to RetGC to be transported. We gain further insight into the distinctive regulatory steps of GCAP2 distribution, by showing that a phosphomimic at position 201 is sufficient to retain GCAP2 at proximal compartments; and that the bovine equivalent to blindness-causative mutation G157R/GCAP2 results in enhanced phosphorylation in vitro and significant retention at the inner segment in vivo, as likely contributing factors to the pathophysiology.

Calculation of absolute protein-ligand binding free energy using distributed replica sampling.

PubMed

Rodinger, Tomas; Howell, P Lynne; Pomès, Régis

2008-10-21

Distributed replica sampling [T. Rodinger et al., J. Chem. Theory Comput. 2, 725 (2006)] is a simple and general scheme for Boltzmann sampling of conformational space by computer simulation in which multiple replicas of the system undergo a random walk in reaction coordinate or temperature space. Individual replicas are linked through a generalized Hamiltonian containing an extra potential energy term or bias which depends on the distribution of all replicas, thus enforcing the desired sampling distribution along the coordinate or parameter of interest regardless of free energy barriers. In contrast to replica exchange methods, efficient implementation of the algorithm does not require synchronicity of the individual simulations. The algorithm is inherently suited for large-scale simulations using shared or heterogeneous computing platforms such as a distributed network. In this work, we build on our original algorithm by introducing Boltzmann-weighted jumping, which allows moves of a larger magnitude and thus enhances sampling efficiency along the reaction coordinate. The approach is demonstrated using a realistic and biologically relevant application; we calculate the standard binding free energy of benzene to the L99A mutant of T4 lysozyme. Distributed replica sampling is used in conjunction with thermodynamic integration to compute the potential of mean force for extracting the ligand from protein and solvent along a nonphysical spatial coordinate. Dynamic treatment of the reaction coordinate leads to faster statistical convergence of the potential of mean force than a conventional static coordinate, which suffers from slow transitions on a rugged potential energy surface.

Calculation of absolute protein-ligand binding free energy using distributed replica sampling

NASA Astrophysics Data System (ADS)

Rodinger, Tomas; Howell, P. Lynne; Pomès, Régis

2008-10-01

Distributed replica sampling [T. Rodinger et al., J. Chem. Theory Comput. 2, 725 (2006)] is a simple and general scheme for Boltzmann sampling of conformational space by computer simulation in which multiple replicas of the system undergo a random walk in reaction coordinate or temperature space. Individual replicas are linked through a generalized Hamiltonian containing an extra potential energy term or bias which depends on the distribution of all replicas, thus enforcing the desired sampling distribution along the coordinate or parameter of interest regardless of free energy barriers. In contrast to replica exchange methods, efficient implementation of the algorithm does not require synchronicity of the individual simulations. The algorithm is inherently suited for large-scale simulations using shared or heterogeneous computing platforms such as a distributed network. In this work, we build on our original algorithm by introducing Boltzmann-weighted jumping, which allows moves of a larger magnitude and thus enhances sampling efficiency along the reaction coordinate. The approach is demonstrated using a realistic and biologically relevant application; we calculate the standard binding free energy of benzene to the L99A mutant of T4 lysozyme. Distributed replica sampling is used in conjunction with thermodynamic integration to compute the potential of mean force for extracting the ligand from protein and solvent along a nonphysical spatial coordinate. Dynamic treatment of the reaction coordinate leads to faster statistical convergence of the potential of mean force than a conventional static coordinate, which suffers from slow transitions on a rugged potential energy surface.

Young, Drunk, Dangerous and Driving: Underage Drinking and Driving Research Findings.

ERIC Educational Resources Information Center

Little, Robert; Clontz, Kenneth

1994-01-01

Summarizes major, recent research findings concerning illegal alcohol use and intoxicated driving among American youth. Examines what research revealed about the nature of underage drinking and driving; what health, social, and legal ramifications are associated with drinking and driving; and what characteristics and behavioral patterns are found…

Changes in Protein Structure and Distribution Observed at Pre-Clinical Stages of Scrapie Pathogenesis

PubMed Central

Kretlow, Ariane; Wang, Qi; Beekes, Michael; Naumann, Dieter; Miller, Lisa M.

2011-01-01

Scrapie is a neurodegenerative disorder that involves the misfolding, aggregation and accumulation of the prion protein (PrP). The normal cellular PrP (PrPC) is rich in α-helical secondary structure, whereas the disease-associated pathogenic form of the protein (PrPSc) has an anomalously high β-sheet content. In this study, protein structural changes were examined in situ in the dorsal root ganglia from perorally 263K scrapie-infected and mock-infected hamsters using synchrotron Fourier Transform InfraRed Microspectroscopy (FTIRM) at four time points over the course of the disease (preclinical, 100 & 130 days post-infection (dpi); first clinical signs (~145 dpi); and terminal (~170 dpi)). Results showed clear changes in the total protein content, structure, and distribution as the disease progressed. At pre-clinical time points, the scrapie-infected animals exhibited a significant increase in protein expression, but the β-sheet protein content was significantly lower than controls. Based on these findings, we suggest that the pre-clinical stages of scrapie are characterized by an overexpression of proteins low in β-sheet content. As the disease progressed, the β-sheet content increased significantly. Immunostaining with a PrP-specific antibody, 3F4, confirmed that this increase was partly – but not solely – due to the formation of PrPSc in the tissue and indicated that other proteins high in β-sheet were produced, either by overexpression or misfolding. Elevated β-sheet was observed near the cell membrane at pre-clinical time points and also in the cytoplasm of infected neurons at later stages of infection. At the terminal stage of the disease, the protein expression declined significantly, likely due to degeneration and death of neurons. These dramatic changes in protein content and structure, especially at pre-clinical time points, emphasize the possibility for identifying other proteins involved in early pathogenesis, which are important for further

Energy efficiency drives the global seasonal distribution of birds.

PubMed

Somveille, Marius; Rodrigues, Ana S L; Manica, Andrea

2018-06-01

The uneven distribution of biodiversity on Earth is one of the most general and puzzling patterns in ecology. Many hypotheses have been proposed to explain it, based on evolutionary processes or on constraints related to geography and energy. However, previous studies investigating these hypotheses have been largely descriptive due to the logistical difficulties of conducting controlled experiments on such large geographical scales. Here, we use bird migration-the seasonal redistribution of approximately 15% of bird species across the world-as a natural experiment for testing the species-energy relationship, the hypothesis that animal diversity is driven by energetic constraints. We develop a mechanistic model of bird distributions across the world, and across seasons, based on simple ecological and energetic principles. Using this model, we show that bird species distributions optimize the balance between energy acquisition and energy expenditure while taking into account competition with other species. These findings support, and provide a mechanistic explanation for, the species-energy relationship. The findings also provide a general explanation of migration as a mechanism that allows birds to optimize their energy budget in the face of seasonality and competition. Finally, our mechanistic model provides a tool for predicting how ecosystems will respond to global anthropogenic change.

HIT'nDRIVE: patient-specific multidriver gene prioritization for precision oncology

PubMed Central

Hodzic, Ermin; Sauerwald, Thomas; Dao, Phuong; Wang, Kendric; Yeung, Jake; Anderson, Shawn; Vandin, Fabio; Haffari, Gholamreza; Collins, Colin C.; Sahinalp, S. Cenk

2017-01-01

Prioritizing molecular alterations that act as drivers of cancer remains a crucial bottleneck in therapeutic development. Here we introduce HIT'nDRIVE, a computational method that integrates genomic and transcriptomic data to identify a set of patient-specific, sequence-altered genes, with sufficient collective influence over dysregulated transcripts. HIT'nDRIVE aims to solve the “random walk facility location” (RWFL) problem in a gene (or protein) interaction network, which differs from the standard facility location problem by its use of an alternative distance measure: “multihitting time,” the expected length of the shortest random walk from any one of the set of sequence-altered genes to an expression-altered target gene. When applied to 2200 tumors from four major cancer types, HIT'nDRIVE revealed many potentially clinically actionable driver genes. We also demonstrated that it is possible to perform accurate phenotype prediction for tumor samples by only using HIT'nDRIVE-seeded driver gene modules from gene interaction networks. In addition, we identified a number of breast cancer subtype-specific driver modules that are associated with patients’ survival outcome. Furthermore, HIT'nDRIVE, when applied to a large panel of pan-cancer cell lines, accurately predicted drug efficacy using the driver genes and their seeded gene modules. Overall, HIT'nDRIVE may help clinicians contextualize massive multiomics data in therapeutic decision making, enabling widespread implementation of precision oncology. PMID:28768687

Drivers' and non-drivers' performance in a change detection task with static driving scenes: is there a benefit of experience?

PubMed

Zhao, Nan; Chen, Wenfeng; Xuan, Yuming; Mehler, Bruce; Reimer, Bryan; Fu, Xiaolan

2014-01-01

The 'looked-but-failed-to-see' phenomenon is crucial to driving safety. Previous research utilising change detection tasks related to driving has reported inconsistent effects of driver experience on the ability to detect changes in static driving scenes. Reviewing these conflicting results, we suggest that drivers' increased ability to detect changes will only appear when the task requires a pattern of visual attention distribution typical of actual driving. By adding a distant fixation point on the road image, we developed a modified change blindness paradigm and measured detection performance of drivers and non-drivers. Drivers performed better than non-drivers only in scenes with a fixation point. Furthermore, experience effect interacted with the location of the change and the relevance of the change to driving. These results suggest that learning associated with driving experience reflects increased skill in the efficient distribution of visual attention across both the central focus area and peripheral objects. This article provides an explanation for the previously conflicting reports of driving experience effects in change detection tasks. We observed a measurable benefit of experience in static driving scenes, using a modified change blindness paradigm. These results have translational opportunities for picture-based training and testing tools to improve driver skill.

Ocular disease and driving.

PubMed

Wood, Joanne M; Black, Alex A

2016-09-01

As the driving population ages, the number of drivers with visual impairment resulting from ocular disease will increase given the age-related prevalence of ocular disease. The increase in visual impairment in the driving population has a number of implications for driving outcomes. This review summarises current research regarding the impact of common ocular diseases on driving ability and safety, with particular focus on cataract, glaucoma, age-related macular degeneration, hemianopia and diabetic retinopathy. The evidence considered includes self-reported driving outcomes, driving performance (on-road and simulator-based) and various motor vehicle crash indices. Collectively, this review demonstrates that driving ability and safety are negatively affected by ocular disease; however, further research is needed in this area. Older drivers with ocular disease need to be aware of the negative consequences of their ocular condition and in the case where treatment options are available, encouraged to seek these earlier for optimum driving safety and quality of life benefits. © 2016 Optometry Australia.

Driving and Neurodegenerative Diseases

PubMed Central

Uc, Ergun Y.; Rizzo, Matthew

2011-01-01

The proportion of elderly in the general population is rising, resulting in greater numbers of drivers with neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). These neurodegenerative disorders impair cognition, visual perception, and motor function, leading to reduced driver fitness and greater crash risk. Yet medical diagnosis or age alone is not reliable enough to predict driver safety or crashes, or revoke the driving privileges of these drivers. Driving research utilizes tools such as questionnaires about driving habits and history, driving simulators, standardized road tests utilizing instrumented vehicles, and state driving records. Research challenges include outlining the evolution of driving safety, understanding the mechanisms of driving impairment, and developing a reliable and efficient standardized test battery for prediction of driver safety in neurodegenerative disorders. This information will enable healthcare providers to advise their patients with neurodegenerative disorders with more certainty, affect policy, and help to develop rehabilitative measures for driving. PMID:18713573

Disulfide bridge regulates ligand-binding site selectivity in liver bile acid-binding proteins.

PubMed

Cogliati, Clelia; Tomaselli, Simona; Assfalg, Michael; Pedò, Massimo; Ferranti, Pasquale; Zetta, Lucia; Molinari, Henriette; Ragona, Laura

2009-10-01

Bile acid-binding proteins (BABPs) are cytosolic lipid chaperones that play central roles in driving bile flow, as well as in the adaptation to various pathological conditions, contributing to the maintenance of bile acid homeostasis and functional distribution within the cell. Understanding the mode of binding of bile acids with their cytoplasmic transporters is a key issue in providing a model for the mechanism of their transfer from the cytoplasm to the nucleus, for delivery to nuclear receptors. A number of factors have been shown to modulate bile salt selectivity, stoichiometry, and affinity of binding to BABPs, e.g. chemistry of the ligand, protein plasticity and, possibly, the formation of disulfide bridges. Here, the effects of the presence of a naturally occurring disulfide bridge on liver BABP ligand-binding properties and backbone dynamics have been investigated by NMR. Interestingly, the disulfide bridge does not modify the protein-binding stoichiometry, but has a key role in modulating recognition at both sites, inducing site selectivity for glycocholic and glycochenodeoxycholic acid. Protein conformational changes following the introduction of a disulfide bridge are small and located around the inner binding site, whereas significant changes in backbone motions are observed for several residues distributed over the entire protein, both in the apo form and in the holo form. Site selectivity appears, therefore, to be dependent on protein mobility rather than being governed by steric factors. The detected properties further establish a parallelism with the behaviour of human ileal BABP, substantiating the proposal that BABPs have parallel functions in hepatocytes and enterocytes.

Assessing the driving performance of older adult drivers: on-road versus simulated driving.

PubMed

Lee, Hoe C; Cameron, Don; Lee, Andy H

2003-09-01

To validate a laboratory-based driving simulator in measuring on-road driving performance, 129 older adult drivers were assessed with both the simulator and an on-road test. The driving performance of the participants was gauged by appropriate and reliable age-specific assessment criteria, which were found to be negatively correlated with age. Using principal component analysis, two performance indices were developed from the criteria to represent the overall performance in simulated driving and the on-road assessment. There was significant positive association between the two indices, with the simulated driving performance index explaining over two-thirds of the variability of the on-road driving performance index, after adjustment for age and gender of the drivers. The results supported the validity of the driving simulator and it is a safer and more economical method than the on-road testing to assess the driving performance of older adult drivers.

Rapid comparison of protein binding site surfaces with Property Encoded Shape Distributions (PESD)

PubMed Central

Das, Sourav; Kokardekar, Arshad

2009-01-01

Patterns in shape and property distributions on the surface of binding sites are often conserved across functional proteins without significant conservation of the underlying amino-acid residues. To explore similarities of these sites from the viewpoint of a ligand, a sequence and fold-independent method was created to rapidly and accurately compare binding sites of proteins represented by property-mapped triangulated Gauss-Connolly surfaces. Within this paradigm, signatures for each binding site surface are produced by calculating their property-encoded shape distributions (PESD), a measure of the probability that a particular property will be at a specific distance to another on the molecular surface. Similarity between the signatures can then be treated as a measure of similarity between binding sites. As postulated, the PESD method rapidly detected high levels of similarity in binding site surface characteristics even in cases where there was very low similarity at the sequence level. In a screening experiment involving each member of the PDBBind 2005 dataset as a query against the rest of the set, PESD was able to retrieve a binding site with identical E.C. (Enzyme Commission) numbers as the top match in 79.5% of cases. The ability of the method in detecting similarity in binding sites with low sequence conservations were compared with state-of-the-art binding site comparison methods. PMID:19919089

Heterogeneous distribution of G protein alpha subunits in the main olfactory and vomeronasal systems of Rhinella (Bufo) arenarum tadpoles.

PubMed

Jungblut, Lucas D; Paz, Dante A; López-Costa, Juan J; Pozzi, Andrea G

2009-10-01

We evaluated the presence of G protein subtypes Galpha(o), Galpha(i2), and Galpha(olf) in the main olfactory system (MOS) and accessory or vomeronasal system (VNS) of Rhinella (Bufo) arenarum tadpoles, and here describe the fine structure of the sensory cells in the olfactory epithelium (OE) and vomeronasal organ (VNO). The OE shows olfactory receptor neurons (ORNs) with cilia in the apical surface, and the vomeronasal receptor neurons (VRNs) of the VNO are covered with microvilli. Immunohistochemistry detected the presence of at least two segregated populations of ORNs throughout the OE, coupled to Galpha(olf) and Galpha(o). An antiserum against Galpha(i2) was ineffective in staining the ORNs. In the VNO, Galpha(o) neurons stained strongly but lacked immunoreactivity to any other Galpha subunit in all larval stages analyzed. Western blot analyses and preabsorption experiments confirmed the specificity of the commercial antisera used. The functional significance of the heterogeneous G-protein distribution in R. arenarum tadpoles is not clear, but the study of G- protein distributions in various amphibian species is important, since this vertebrate group played a key role in the evolution of tetrapods. A more complete knowledge of the amphibian MOS and VNS would help to understand the functional organization and evolution of vertebrate chemosensory systems. This work demonstrates, for the first time, the existence of a segregated distribution of G-proteins in the OE of R. arenarum tadpoles.

Subcellular distribution of human RDM1 protein isoforms and their nucleolar accumulation in response to heat shock and proteotoxic stress.

PubMed

Messaoudi, Lydia; Yang, Yun-Gui; Kinomura, Aiko; Stavreva, Diana A; Yan, Gonghong; Bortolin-Cavaillé, Marie-Line; Arakawa, Hiroshi; Buerstedde, Jean-Marie; Hainaut, Pierre; Cavaillé, Jérome; Takata, Minoru; Van Dyck, Eric

2007-01-01

The RDM1 gene encodes a RNA recognition motif (RRM)-containing protein involved in the cellular response to the anti-cancer drug cisplatin in vertebrates. We previously reported a cDNA encoding the full-length human RDM1 protein. Here, we describe the identification of 11 human cDNAs encoding RDM1 protein isoforms. This repertoire is generated by alternative pre-mRNA splicing and differential usage of two translational start sites, resulting in proteins with long or short N-terminus and a great diversity in the exonic composition of their C-terminus. By using tagged proteins and fluorescent microscopy, we examined the subcellular distribution of full-length RDM1 (renamed RDM1alpha), and other RDM1 isoforms. We show that RDM1alpha undergoes subcellular redistribution and nucleolar accumulation in response to proteotoxic stress and mild heat shock. In unstressed cells, the long N-terminal isoforms displayed distinct subcellular distribution patterns, ranging from a predominantly cytoplasmic to almost exclusive nuclear localization, suggesting functional differences among the RDM1 proteins. However, all isoforms underwent stress-induced nucleolar accumulation. We identified nuclear and nucleolar localization determinants as well as domains conferring cytoplasmic retention to the RDM1 proteins. Finally, RDM1 null chicken DT40 cells displayed an increased sensitivity to heat shock, compared to wild-type (wt) cells, suggesting a function for RDM1 in the heat-shock response.

Proactive vs. reactive car driving: EEG evidence for different driving strategies of older drivers

PubMed Central

Wascher, Edmund; Getzmann, Stephan

2018-01-01

Aging is associated with a large heterogeneity in the extent of age-related changes in sensory, motor, and cognitive functions. All these functions can influence the performance in complex tasks like car driving. The present study aims to identify potential differences in underlying cognitive processes that may explain inter-individual variability in driving performance. Younger and older participants performed a one-hour monotonous driving task in a driving simulator under varying crosswind conditions, while behavioral and electrophysiological data were recorded. Overall, younger and older drivers showed comparable driving performance (lane keeping). However, there was a large difference in driving lane variability within the older group. Dividing the older group in two subgroups with low vs. high driving lane variability revealed differences between the two groups in electrophysiological correlates of mental workload, consumption of mental resources, and activation and sustaining of attention: Older drivers with high driving lane variability showed higher frontal Alpha and Theta activity than older drivers with low driving lane variability and—with increasing crosswind—a more pronounced decrease in Beta activity. These results suggest differences in driving strategies of older and younger drivers, with the older drivers using either a rather proactive and alert driving strategy (indicated by low driving lane variability and lower Alpha and Beta activity), or a rather reactive strategy (indicated by high driving lane variability and higher Alpha activity). PMID:29352314

Positive effects of Red Bull® Energy Drink on driving performance during prolonged driving.

PubMed

Mets, Monique A J; Ketzer, Sander; Blom, Camilla; van Gerven, Maartje H; van Willigenburg, Gitta M; Olivier, Berend; Verster, Joris C

2011-04-01

The purpose of this study was to examine if Red Bull® Energy Drink can counteract sleepiness and driving impairment during prolonged driving. Twenty-four healthy volunteers participated in this double-blind placebo-controlled crossover study. After 2 h of highway driving in the STISIM driving simulator, subjects had a 15-min break and consumed Red Bull® Energy Drink (250 ml) or placebo (Red Bull® Energy Drink without the functional ingredients: caffeine, taurine, glucuronolactone, B vitamins (niacin, pantothenic acid, B6, B12), and inositol) before driving for two additional hours. A third condition comprised 4 h of uninterrupted driving. Primary parameter was the standard deviation of lateral position (SDLP), i.e., the weaving of the car. Secondary parameters included SD speed, subjective driving quality, sleepiness, and mental effort to perform the test. No significant differences were observed during the first 2 h of driving. Red Bull® Energy Drink significantly improved driving relative to placebo: SDLP was significantly reduced during the 3rd (p < 0.046) and 4th hour of driving (p < 0.011). Red Bull® Energy Drink significantly reduced the standard deviation of speed (p < 0.004), improved subjective driving quality (p < 0.0001), and reduced mental effort to perform the test (p < 0.024) during the 3rd hour of driving. Subjective sleepiness was significantly decreased during both the 3rd and 4th hour of driving after Red Bull® Energy Drink (p < 0.001 and p < 0.009, respectively). Relative to uninterrupted driving, Red Bull® Energy Drink significantly improved each parameter. Red Bull® Energy Drink significantly improves driving performance and reduces driver sleepiness during prolonged highway driving.

The Ubiquitous Distribution of Late Embryogenesis Abundant Proteins across Cell Compartments in Arabidopsis Offers Tailored Protection against Abiotic Stress[C][W][OPEN

PubMed Central

Candat, Adrien; Paszkiewicz, Gaël; Neveu, Martine; Gautier, Romain; Logan, David C.; Avelange-Macherel, Marie-Hélène; Macherel, David

2014-01-01

Late embryogenesis abundant (LEA) proteins are hydrophilic, mostly intrinsically disordered proteins, which play major roles in desiccation tolerance. In Arabidopsis thaliana, 51 genes encoding LEA proteins clustered into nine families have been inventoried. To increase our understanding of the yet enigmatic functions of these gene families, we report the subcellular location of each protein. Experimental data highlight the limits of in silico predictions for analysis of subcellular localization. Thirty-six LEA proteins localized to the cytosol, with most being able to diffuse into the nucleus. Three proteins were exclusively localized in plastids or mitochondria, while two others were found dually targeted to these organelles. Targeting cleavage sites could be determined for five of these proteins. Three proteins were found to be endoplasmic reticulum (ER) residents, two were vacuolar, and two were secreted. A single protein was identified in pexophagosomes. While most LEA protein families have a unique subcellular localization, members of the LEA_4 family are widely distributed (cytosol, mitochondria, plastid, ER, and pexophagosome) but share the presence of the class A α-helix motif. They are thus expected to establish interactions with various cellular membranes under stress conditions. The broad subcellular distribution of LEA proteins highlights the requirement for each cellular compartment to be provided with protective mechanisms to cope with desiccation or cold stress. PMID:25005920

Evaluation of methods for the assessment of attention while driving.

PubMed

Kircher, Katja; Ahlstrom, Christer

2018-05-01

The ability to assess the current attentional state of the driver is important for many aspects of driving, not least in the field of partial automation for transfer of control between vehicle and driver. Knowledge about the driver's attentional state is also necessary for the assessment of the effects of additional tasks on attention. The objective of this paper is to evaluate different methods that can be used to assess attention, first theoretically, and then empirically in a controlled field study and in the laboratory. Six driving instructors participated in all experimental conditions of the study, delivering within-subjects data for all tested methods. Additional participants were recruited for some of the conditions. The test route consisted of 14km of motorway with low to moderate traffic, which was driven three times per participant per condition. The on-road conditions were: baseline, driving with eye tracking and self-paced visual occlusion, and driving while thinking aloud. The laboratory conditions were: Describing how attention should be distributed on a motorway, and thinking aloud while watching a video from the baseline drive. The results show that visual occlusion, especially in combination with eye tracking, was appropriate for assessing spare capacity. The think aloud protocol was appropriate to gain insight about the driver's actual mental representation of the situation at hand. Expert judgement in the laboratory was not reliable for the assessment of drivers' attentional distribution in traffic. Across all assessment techniques, it is evident that meaningful assessment of attention in a dynamic traffic situation can only be achieved when the infrastructure layout, surrounding road users, and intended manoeuvres are taken into account. This requires advanced instrumentation of the vehicle, and subsequent data reduction, analysis and interpretation are demanding. In conclusion, driver attention assessment in real traffic is a complex task, but

Spinal interneurons differentiate sequentially from those driving the fastest swimming movements in larval zebrafish to those driving the slowest ones.

PubMed

McLean, David L; Fetcho, Joseph R

2009-10-28

Studies of neuronal networks have revealed few general principles that link patterns of development with later functional roles. While investigating the neural control of movements, we recently discovered a topographic map in the spinal cord of larval zebrafish that relates the position of motoneurons and interneurons to their order of recruitment during swimming. Here, we show that the map reflects an orderly pattern of differentiation of neurons driving different movements. First, we use high-speed filming to show that large-amplitude swimming movements with bending along much of the body appear first, with smaller, regional swimming movements emerging later. Next, using whole-cell patch recordings, we demonstrate that the excitatory circuits that drive large-amplitude, fast swimming movements at larval stages are present and functional early on in embryos. Finally, we systematically assess the orderly emergence of spinal circuits according to swimming speed using transgenic fish expressing the photoconvertible protein Kaede to track neuronal differentiation in vivo. We conclude that a simple principle governs the development of spinal networks in which the neurons driving the fastest, most powerful swimming in larvae develop first with ones that drive increasingly weaker and slower larval movements layered on over time. Because the neurons are arranged by time of differentiation in the spinal cord, the result is a topographic map that represents the speed/strength of movements at which neurons are recruited and the temporal emergence of networks. This pattern may represent a general feature of neuronal network development throughout the brain and spinal cord.

To acquire more detailed radiation drive by use of ``quasi-steady'' approximation in atomic kinetics

NASA Astrophysics Data System (ADS)

Ren, Guoli; Pei, Wenbing; Lan, Ke; Gu, Peijun; Li, Xin

2012-10-01

In current routine 2D simulation of hohlraum physics, we adopt the principal-quantum- number(n-level) average atom model(AAM) in NLTE plasma description. However, the detailed experimental frequency-dependant radiative drive differs from our n-level simulated drive, which reminds us the need of a more detailed atomic kinetics description. The orbital-quantum- number(nl-level) average atom model is a natural consideration, however the nl-level in-line calculation needs much more computational resource. By distinguishing the rapid bound-bound atomic processes from the relative slow bound-free atomic processes, we found a method to build up a more detailed bound electron distribution(nl-level even nlm-level) using in-line n-level calculated plasma conditions(temperature, density, and average ionization degree). We name this method ``quasi-steady approximation'' in atomic kinetics. Using this method, we re-build the nl-level bound electron distribution (Pnl), and acquire a new hohlraum radiative drive by post-processing. Comparison with the n-level post-processed hohlraum drive shows that we get an almost identical radiation flux but with more fine frequency-denpending spectrum structure which appears only in nl-level transition with same n number(n=0) .

Drive for muscularity and drive for thinness: the impact of pro-anorexia websites.

PubMed

Juarez, Lilia; Soto, Ernesto; Pritchard, Mary E

2012-01-01

In recent years, websites that stress the message of thinness as the ideal and only choice have surfaced on the internet. The possibility that pro-anorexia websites may reinforce restrictive eating and exercise behaviors is an area of concern. In addition, friends may be influencing one another to view these websites, further contributing to drive for thinness in women and drive for muscularity in men. Three hundred male and female undergraduate psychology students responded to questionnaires assessing: internalization of pro-anorexia website content, internalization of general media content, influence of friends to view pro-anorexia websites, peer influence, drive for muscularity, and drive for thinness. Results showed internalization of pro-anorexia website content was positively correlated with drive for thinness in women, and negatively correlated with drive for muscularity in men. Internalization of pro-anorexia website content was found to be related to both drive for thinness in women and drive for muscularity in men.

Reading Text While Driving

PubMed Central

Horrey, William J.; Hoffman, Joshua D.

2015-01-01

Objective In this study, we investigated how drivers adapt secondary-task initiation and time-sharing behavior when faced with fluctuating driving demands. Background Reading text while driving is particularly detrimental; however, in real-world driving, drivers actively decide when to perform the task. Method In a test track experiment, participants were free to decide when to read messages while driving along a straight road consisting of an area with increased driving demands (demand zone) followed by an area with low demands. A message was made available shortly before the vehicle entered the demand zone. We manipulated the type of driving demands (baseline, narrow lane, pace clock, combined), message format (no message, paragraph, parsed), and the distance from the demand zone when the message was available (near, far). Results In all conditions, drivers started reading messages (drivers’ first glance to the display) before entering or before leaving the demand zone but tended to wait longer when faced with increased driving demands. While reading messages, drivers looked more or less off road, depending on types of driving demands. Conclusions For task initiation, drivers avoid transitions from low to high demands; however, they are not discouraged when driving demands are already elevated. Drivers adjust time-sharing behavior according to driving demands while performing secondary tasks. Nonetheless, such adjustment may be less effective when total demands are high. Application This study helps us to understand a driver’s role as an active controller in the context of distracted driving and provides insights for developing distraction interventions. PMID:25850162

Current Drive

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

Faulconer, D.W

2004-03-15

Certain devices aimed at magnetic confinement of thermonuclear plasma rely on the steady flow of an electric current in the plasma. In view of the dominant place it occupies in both the world magnetic-confinement fusion effort and the author's own activity, the tokamak toroidal configuration is selected as prototype for discussing the question of how such a current can be maintained. Tokamaks require a stationary toroidal plasma current, this being traditionally provided by a pulsed magnetic induction which drives the plasma ring as the secondary of a transformer. Since this mechanism is essentially transient, and steady-state fusion reactor operation hasmore » manifold advantages, significant effort is now devoted to developing alternate steady-state means of generating toroidal current. These methods are classed under the global heading of 'noninductive current drive' or simply 'current drive', generally, though not exclusively, employing the injection of waves and/or toroidally directed particle beams. In what follows we highlight the physical mechanisms underlying surprisingly various approaches to driving current in a tokamak, downplaying a number of practical and technical issues. When a significant data base exists for a given method, its experimental current drive efficiency and future prospects are detailed.« less

SUPERNOVA DRIVING. II. COMPRESSIVE RATIO IN MOLECULAR-CLOUD TURBULENCE

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

Pan, Liubin; Padoan, Paolo; Haugbølle, Troels

2016-07-01

The compressibility of molecular cloud (MC) turbulence plays a crucial role in star formation models, because it controls the amplitude and distribution of density fluctuations. The relation between the compressive ratio (the ratio of powers in compressive and solenoidal motions) and the statistics of turbulence has been previously studied systematically only in idealized simulations with random external forces. In this work, we analyze a simulation of large-scale turbulence (250 pc) driven by supernova (SN) explosions that has been shown to yield realistic MC properties. We demonstrate that SN driving results in MC turbulence with a broad lognormal distribution of themore » compressive ratio, with a mean value ≈0.3, lower than the equilibrium value of ≈0.5 found in the inertial range of isothermal simulations with random solenoidal driving. We also find that the compressibility of the turbulence is not noticeably affected by gravity, nor are the mean cloud radial (expansion or contraction) and solid-body rotation velocities. Furthermore, the clouds follow a general relation between the rms density and the rms Mach number similar to that of supersonic isothermal turbulence, though with a large scatter, and their average gas density probability density function is described well by a lognormal distribution, with the addition of a high-density power-law tail when self-gravity is included.« less

Supernova Driving. II. Compressive Ratio in Molecular-cloud Turbulence

NASA Astrophysics Data System (ADS)

Pan, Liubin; Padoan, Paolo; Haugbølle, Troels; Nordlund, Åke

2016-07-01

The compressibility of molecular cloud (MC) turbulence plays a crucial role in star formation models, because it controls the amplitude and distribution of density fluctuations. The relation between the compressive ratio (the ratio of powers in compressive and solenoidal motions) and the statistics of turbulence has been previously studied systematically only in idealized simulations with random external forces. In this work, we analyze a simulation of large-scale turbulence (250 pc) driven by supernova (SN) explosions that has been shown to yield realistic MC properties. We demonstrate that SN driving results in MC turbulence with a broad lognormal distribution of the compressive ratio, with a mean value ≈0.3, lower than the equilibrium value of ≈0.5 found in the inertial range of isothermal simulations with random solenoidal driving. We also find that the compressibility of the turbulence is not noticeably affected by gravity, nor are the mean cloud radial (expansion or contraction) and solid-body rotation velocities. Furthermore, the clouds follow a general relation between the rms density and the rms Mach number similar to that of supersonic isothermal turbulence, though with a large scatter, and their average gas density probability density function is described well by a lognormal distribution, with the addition of a high-density power-law tail when self-gravity is included.

Drinking-and-Driving-Related Cognitions Mediate the Relationship Between Alcohol Demand and Alcohol-Impaired Driving.

PubMed

Amlung, Michael; Morris, David H; Hatz, Laura E; Teeters, Jenni B; Murphy, James G; McCarthy, Denis M

2016-07-01

Elevated behavioral economic demand for alcohol has been shown to be associated with drinking and driving in college students. The present study sought to clarify the underlying mechanisms of this relationship by examining whether drinking-and-driving-related cognitions (e.g., attitudes, perceptions, and normative beliefs) mediate the association between alcohol demand and drinking and driving. A total of 134 young adult social drinkers completed an alcohol purchase task and measures of perceived dangerousness of drinking and driving, normative beliefs about drinking and driving, and perceived driving limit (i.e., perceived number of drinks one could consume and still drive safely). The frequency of drinking and driving in the past year was assessed via self-report. Individuals who reported drinking and driving exhibited greater alcohol demand (intensity, Omax, and elasticity) compared with those who did not engage in drinking and driving. Increased demand was also correlated with more favorable drinking-and-driving cognitions. Indirect effects tests revealed that perceived driving limit partially mediated the relationship between alcohol demand and drinking-and-driving behavior, even after accounting for drinking level, sex, and delay discounting. These findings provide further support for the utility of behavioral economic theory in understanding drinking-and-driving behavior. In particular, they provide evidence for one mechanism-drinking-and-driving-related cognitions-by which alcohol demand influences drinking and driving. Additional research using longitudinal and experimental designs is required to confirm this model and to identify other potential mediators.

Lipid and protein composition as driving force for multiple sclerosis

NASA Astrophysics Data System (ADS)

Beck, Roy; Shaharabani, Rona

Physical models and experiments often reduce the number of components aiming to address the fundamental mechanisms. Nevertheless, the inherent heterogeneity is an essential ingredient in the biological context. We present our recent efforts to model and understand the development of multiple sclerosis (MS) from a biophysical perspective. Myelin sheath is a multilamellar complex of various lipids and proteins that surround axons and acts as an insulating layer for proper nerve conduction. In MS the myelin structure is disrupted impairing its function. Previous studies showed that MS is correlated with small lipid composition variation and reduction in the adhesive myelin basic protein. We found that such alterations result in pathological phase transition from a lamellar to inverted hexagonal that involve enhanced local curvature. Similar curvatures are also found in vivo in diseased myelin sheaths. Since the etiology and recovery pathways of MS are currently unclear, these findings delineate novel functional roles to dominant constituents in cytoplasmic myelin sheaths, shed new light on mechanisms disrupting lipid-protein complexes, and suggest new courses for diagnosis and treatment for MS.

Linear Back-Drive Differentials

NASA Technical Reports Server (NTRS)

Waydo, Peter

2003-01-01

Linear back-drive differentials have been proposed as alternatives to conventional gear differentials for applications in which there is only limited rotational motion (e.g., oscillation). The finite nature of the rotation makes it possible to optimize a linear back-drive differential in ways that would not be possible for gear differentials or other differentials that are required to be capable of unlimited rotation. As a result, relative to gear differentials, linear back-drive differentials could be more compact and less massive, could contain fewer complex parts, and could be less sensitive to variations in the viscosities of lubricants. Linear back-drive differentials would operate according to established principles of power ball screws and linear-motion drives, but would utilize these principles in an innovative way. One major characteristic of such mechanisms that would be exploited in linear back-drive differentials is the possibility of designing them to drive or back-drive with similar efficiency and energy input: in other words, such a mechanism can be designed so that a rotating screw can drive a nut linearly or the linear motion of the nut can cause the screw to rotate. A linear back-drive differential (see figure) would include two collinear shafts connected to two parts that are intended to engage in limited opposing rotations. The linear back-drive differential would also include a nut that would be free to translate along its axis but not to rotate. The inner surface of the nut would be right-hand threaded at one end and left-hand threaded at the opposite end to engage corresponding right- and left-handed threads on the shafts. A rotation and torque introduced into the system via one shaft would drive the nut in linear motion. The nut, in turn, would back-drive the other shaft, creating a reaction torque. Balls would reduce friction, making it possible for the shaft/nut coupling on each side to operate with 90 percent efficiency.

Carryover effects of highly automated convoy driving on subsequent manual driving performance.

PubMed

Skottke, Eva-Maria; Debus, Günter; Wang, Lei; Huestegge, Lynn

2014-11-01

In the present study, we tested to what extent highly automated convoy driving involving small spacing ("platooning") may affect time headway (THW) and standard deviation of lateral position (SDLP) during subsequent manual driving. Although many previous studies have reported beneficial effects of automated driving, some research has also highlighted potential drawbacks, such as increased speed and reduced THW during the activation of semiautomated driving systems. Here, we rather focused on the question of whether switching from automated to manual driving may produce unwanted carryover effects on safety-relevant driving performance. We utilized a pre-post simulator design to measure THW and SDLP after highly automated driving and compared the data with those for a control group (manual driving throughout). Our data revealed that THW was reduced and SDLP increased after leaving the automation mode. A closer inspection of the data suggested that specifically the effect on THW is likely due to sensory and/or cognitive adaptation processes. Behavioral adaptation effects need to be taken into account in future implementations of automated convoy systems. Potential application areas of this research comprise automated freight traffic (truck convoys) and the design of driver assistance systems in general. Potential countermeasures against following at short distance as behavioral adaptation should be considered.

Association between alcohol-impaired driving enforcement-related strategies and alcohol-impaired driving.

PubMed

Sanem, Julia R; Erickson, Darin J; Rutledge, Patricia C; Lenk, Kathleen M; Nelson, Toben F; Jones-Webb, Rhonda; Toomey, Traci L

2015-05-01

All states in the U.S. prohibit alcohol-impaired driving but active law enforcement is necessary for effectively reducing this behavior. Sobriety checkpoints, saturation patrols, open container laws, and media campaigns related to enforcement efforts are all enforcement-related strategies for reducing alcohol-impaired driving. We conducted surveys of all state patrol agencies and a representative sample of local law enforcement agencies to assess their use of alcohol-impaired driving enforcement-related strategies and to determine the relationship between these enforcement-related strategies and self-reported alcohol-impaired driving behavior obtained from the Behavioral Risk Factor Surveillance System. We found that sobriety checkpoints, saturation patrols, and enforcement of open container laws were associated with a lower prevalence of alcohol-impaired driving but, more importantly, a combination of enforcement-related strategies was associated with a greater decrease in alcohol-impaired driving than any individual enforcement-related activity. In addition, alcohol-impaired driving enforcement-related strategies were associated with decreased alcohol-impaired driving above and beyond their association with decreased binge drinking. Results suggest law enforcement agencies should give greater priority to using a combination of strategies rather than relying on any one individual enforcement activity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Driving and dementia: Efficient approach to driving safety concerns in family practice.

PubMed

Lee, Linda; Molnar, Frank

2017-01-01

To provide primary care physicians with an approach to driving safety concerns when older persons present with memory difficulties. The approach is based on an accredited memory clinic training program developed by the Centre for Family Medicine Primary Care Collaborative Memory Clinic. One of the most challenging aspects of dementia care is the assessment of driving safety. Drivers with dementia are at higher risk of motor vehicle collisions, yet many drivers with mild dementia might be safely able to continue driving for several years. Because safe driving is dependent on multiple cognitive and functional skills, clinicians should carefully consider many factors when determining if cognitive concerns affect driving safety. Specific findings on corroborated history and office-based cognitive testing might aid in the physician's decisions to refer for comprehensive on-road driving evaluation and whether to notify transportation authorities in accordance with provincial reporting requirements. Sensitive communication and a person-centred approach are essential. Primary care physicians must consider many factors when determining if cognitive concerns might affect driving safety in older drivers. Copyright© the College of Family Physicians of Canada.

The relationship between impaired driving crashes and beliefs about impaired driving: do residents in high crash rate counties have greater concerns about impaired driving?

PubMed

Beck, Kenneth H; Yan, Alice F; Wang, Min Qi; Kerns, Timothy J; Burch, Cynthia A

2009-04-01

The purpose of this investigation was to examine the relationship between impaired driving crashes and public beliefs and concerns about impaired driving across each of Maryland's twenty-four counties (including Baltimore City). It was hypothesized that residents of counties that experience higher impaired driving crashes would express more concerns about impaired driving and perceive more risks about driving impaired than residents of counties that have lower rates of impaired driving. Data for alcohol impaired driving crashes were obtained for the years 2004-2006. These data were compared to public opinion data that was obtained annually by random-digit-dial telephone surveys from 2004 to 2007. Concerns about drunk driving as well as perceptions of the likelihood of being stopped by the police if one were to drive after having too much to drink were related to counties with higher serious impaired driving crash rates, as were perceptions that the police and the legal system were too lenient. Perceptions about the likelihood of being stopped by the police were higher in those counties with more impaired driving enforcement activity. Perceptions of concern appear to be shaped more by crash exposure than enforcement activity. Campaigns that address impaired driving prevention should substantially increase enforcement, strengthen the adjudication process of impaired drivers, and emphasize the potential seriousness of drinking-driving crashes in their promotional activities.

Support for stroke patients in resumption of driving: patient survey and driving simulator trial

PubMed Central

Hitosugi, Masahito; Takehara, Itaru; Watanabe, Shu; Hayashi, Yasufumi; Tokudome, Shogo

2011-01-01

Background: Encouragement of stroke patients to resume driving is important to promote their reintegration into the community. Limited rehabilitation has been performed in this regard, owing to lack of specific knowledge on the part of medical staff. To establish an effective support program for stroke patients who wish to resume driving, we propose comprehensive training by medical staff using a driving simulator. Methods: A survey of stroke patients admitted to the Tokyo Metropolitan Rehabilitation Hospital was first performed. A questionnaire was sent to 525 patients. Of 218 responses, the answers of 118 patients who had been driving before their stroke were analyzed. More than 80% of stroke patients did not obtain enough information about resuming driving during their hospital stay, and 38.1% of patients would have liked to have had driving training with a simulator. From these results, we set out to determine the effect of driving training using a realistic and technically advanced driving simulator. Twenty-four stroke patients and 20 healthy controls were included in the study. Results: Repeat training with the simulator resulted in an increased ability to perform braking and an improvement in driving ability. The majority of stroke patients who had the mental and physical ability to drive a car were likely to be assessed as being able to resume driving as a result of the training program. Conclusion: This study indicates that comprehensive support by medical staff and provision of adequate information about resumption of driving and the opportunity for training on a driving simulator are likely to aid resumption of driving by stroke patients, thus enhancing their rehabilitation and social reintegration. PMID:21475633

What Drives Teacher Engagement: A Study of Different Age Cohorts

ERIC Educational Resources Information Center

Guglielmi, Dina; Bruni, Ilaria; Simbula, Silvia; Fraccaroli, Franco; Depolo, Marco

2016-01-01

Despite the growing body of research on work engagement, little is known about what drives work engagement among different age cohorts. This study aims to investigate whether engagement varies across age cohorts and examines the job resources that foster teacher engagement. A questionnaire was distributed to 537 teachers who were employed in…

Dementia and driving.

PubMed

O'Neill, D; Neubauer, K; Boyle, M; Gerrard, J; Surmon, D; Wilcock, G K

1992-04-01

Many European countries test cars, but not their drivers, as they age. There is evidence to suggest that human factors are more important than vehicular factors as causes of motor crashes. The elderly also are involved in more accidents per distance travelled than middle-aged drivers. As the UK relies on self-certification of health by drivers over the age of 70 years, we examined the driving practices of patients with dementia attending a Memory Clinic. Nearly one-fifth of 329 patients with documented dementia continued to drive after the onset of dementia, and impaired driving ability was noted in two-thirds of these. Their families experienced great difficulty in persuading patients to stop driving, and had to invoke outside help in many cases. Neuropsychological tests did not help to identify those who drove badly while activity of daily living scores were related to driving ability. These findings suggest that many patients with dementia drive in an unsafe fashion after the onset of the illness. The present system of self-certification of health by the elderly for driver-licensing purposes needs to be reassessed.

Dementia and driving.

PubMed Central

O'Neill, D; Neubauer, K; Boyle, M; Gerrard, J; Surmon, D; Wilcock, G K

1992-01-01

Many European countries test cars, but not their drivers, as they age. There is evidence to suggest that human factors are more important than vehicular factors as causes of motor crashes. The elderly also are involved in more accidents per distance travelled than middle-aged drivers. As the UK relies on self-certification of health by drivers over the age of 70 years, we examined the driving practices of patients with dementia attending a Memory Clinic. Nearly one-fifth of 329 patients with documented dementia continued to drive after the onset of dementia, and impaired driving ability was noted in two-thirds of these. Their families experienced great difficulty in persuading patients to stop driving, and had to invoke outside help in many cases. Neuropsychological tests did not help to identify those who drove badly while activity of daily living scores were related to driving ability. These findings suggest that many patients with dementia drive in an unsafe fashion after the onset of the illness. The present system of self-certification of health by the elderly for driver-licensing purposes needs to be reassessed. PMID:1433058

Dialling and driving: factors influencing intentions to use a mobile phone while driving.

PubMed

Walsh, Shari P; White, Katherine M; Hyde, Melissa K; Watson, Barry

2008-11-01

Despite being identified as an unsafe (and, in some jurisdictions, illegal) driving practice, the psychological factors underlying people's decision to use their mobile phone while driving have received little attention. The present study utilised the theory of planned behaviour (TPB) to examine the role of attitudes, norms, control factors, and risk perceptions, in predicting people's intentions to use their mobile phone while driving. We examined the predictors of intentions to use a mobile phone while driving in general, and for calling and text messaging in 4 scenarios differing in descriptions of vehicle speed and time pressure. There was some support for the TPB given that attitudes consistently predicted intentions to drive while using a mobile phone and that pressure from significant others (norms) determined some phone use while driving intentions, although less support was found for the role of perceptions of control. Risk was not generally predictive of safer driving intentions. These findings indicate that different factors influence each form of mobile phone use while driving and, hence, a multi-strategy approach is likely to be required to address the issue.

Relationships between frequency of driving under the influence of cannabis, self-reported reckless driving and risk-taking behavior observed in a driving simulator.

PubMed

Bergeron, Jacques; Paquette, Martin

2014-06-01

The role of cannabis consumption in traffic crashes is unclear and the causal link between cannabis and collisions is still to be demonstrated. While cannabis use is very likely to impair driving ability, there is as yet no overwhelming evidence that cannabis use in isolation contributes more to collisions than other characteristics inherent to cannabis users. As noted in a growing body of literature, individuals driving under the influence of cannabis (DUIC) seem to exhibit a general reckless driving style putting them at higher risk to be involved in traffic crashes. This study aims at investigating the relationship between self-reported DUIC and reckless driving by means of self-reported measures and direct observations made in a driving simulator. Participants (n=72) were required to be between 18 and 25 years of age, to hold a valid driver's license, and to drive at least twice a week. They completed standard driving simulation tasks recreating everyday on-road trivial conditions. Results show that people admitting that they commit more real-life dangerous driving behaviors reached higher maximum speed and demonstrated more reckless driving behaviors on the driving simulation tasks. Self-reported DUIC is associated with a risky driving style including a broad range of reckless on-road behaviors and support the problem driving behavior theory. Moreover, beyond confounding factors, both self-report DUIC and observed dangerous behaviors are associated with real-life traffic violations. Since DUIC appears to be related to an overall reckless style of driving, it is proposed that public safety policies should be more holistic, simultaneously targeting multiple on-road dangerous behaviors for intervention. Copyright © 2014 Elsevier B.V. All rights reserved.

Cognitive impairment and driving safety.

PubMed

Eby, David W; Molnar, Lisa J

2012-11-01

As the populations of many countries continue to age, cognitive impairment will likely become more common. Individuals with cognitive impairment pose special challenges for families, health professionals, driving safety professionals, and the larger community, particularly if these older adults depend on driving as their primary means of community mobility. It is vital that we continue to extend our knowledge about the driving behavior of individuals' with cognitive impairment, as well as try to develop effective means of screening and assessing these individuals for fitness to drive and help facilitate their transition to non-driving when appropriate. This special issue is intended to provide researchers and practitioners an opportunity to present the most recent research findings on driving-related issues among older adults with cognitive impairment. The issue contains 11 original contributions from seven countries. The topics covered by these papers are: crash risks; screening, assessment, and fitness to drive; driving performance using a driving simulator; and driving behaviors and driving-related decisions of people with cognitive impairments. Copyright © 2012. Published by Elsevier Ltd.

Text messaging during simulated driving.

PubMed

Drews, Frank A; Yazdani, Hina; Godfrey, Celeste N; Cooper, Joel M; Strayer, David L

2009-10-01

This research aims to identify the impact of text messaging on simulated driving performance. In the past decade, a number of on-road, epidemiological, and simulator-based studies reported the negative impact of talking on a cell phone on driving behavior. However, the impact of text messaging on simulated driving performance is still not fully understood. Forty participants engaged in both a single task (driving) and a dual task (driving and text messaging) in a high-fidelity driving simulator. Analysis of driving performance revealed that participants in the dual-task condition responded more slowly to the onset of braking lights and showed impairments in forward and lateral control compared with a driving-only condition. Moreover, text-messaging drivers were involved in more crashes than drivers not engaged in text messaging. Text messaging while driving has a negative impact on simulated driving performance. This negative impact appears to exceed the impact of conversing on a cell phone while driving. The results increase our understanding of driver distraction and have potential implications for public safety and device development.

State all-driver distracted driving laws and high school students'  texting while driving behavior.

PubMed

Qiao, Nan; Bell, Teresa Maria

2016-01-01

Texting while driving is highly prevalent among adolescents and young adults in the United States. Texting while driving can significantly increase the risk of road crashes and is associated with other risky driving behaviors. Most states have enacted distracted driving laws to prohibit texting while driving. This study examines effects of different all-driver distracted driving laws on texting while driving among high school students. High school student data were extracted from the 2013 National Youth Risk Behavior Survey. Distracted driving law information was collected from the National Conference of State Legislatures. The final sample included 6,168 high school students above the restricted driving age in their states and with access to a vehicle. Logistic regression was applied to estimate odds ratios of laws on texting while driving. All-driver text messaging bans with primary enforcement were associated with a significant reduction in odds of texting while driving among high school students (odds ratio = 0.703; 95% confidence interval, 0.513-0.964), whereas all-driver phone use bans with primary enforcement did not have a significant association with texting while driving (odds ratio = 0.846; 95% confidence interval, 0.501-1.429). The findings indicate that all-driver distracted driving laws that specifically target texting while driving as opposed to all types of phone use are effective in reducing the behavior among high school students.

Using driving simulators to assess driving safety.

PubMed

Boyle, Linda Ng; Lee, John D

2010-05-01

Changes in drivers, vehicles, and roadways pose substantial challenges to the transportation safety community. Crash records and naturalistic driving data are useful for examining the influence of past or existing technology on drivers, and the associations between risk factors and crashes. However, they are limited because causation cannot be established and technology not yet installed in production vehicles cannot be assessed. Driving simulators have become an increasingly widespread tool to understand evolving and novel technologies. The ability to manipulate independent variables in a randomized, controlled setting also provides the added benefit of identifying causal links. This paper introduces a special issue on simulator-based safety studies. The special issue comprises 25 papers that demonstrate the use of driving simulators to address pressing transportation safety problems and includes topics as diverse as neurological dysfunction, work zone design, and driver distraction. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

DRIVE: Drive-Cycle Rapid Investigation, Visualization, and Evaluation

Science.gov Websites

specialized statistical clustering methods. The duration of these representative drive cycles, which aim to , DRIVE can benefit a variety of users. For example: Fleet managers can use the tool to make educated investment decisions by determining, in advance, the payback period for a given technology. Vehicle

Localization of complement factor H gene expression and protein distribution in the mouse outer retina

PubMed Central

Smit-McBride, Zeljka; Oltjen, Sharon L.; Radu, Roxana A.; Estep, Jason; Nguyen, Anthony T.; Gong, Qizhi

2015-01-01

Purpose To determine the localization of complement factor H (Cfh) mRNA and its protein in the mouse outer retina. Methods Quantitative real-time PCR (qPCR) was used to determine the expression of Cfh and Cfh-related (Cfhr) transcripts in the RPE/choroid. In situ hybridization (ISH) was performed using the novel RNAscope 2.0 FFPE assay to localize the expression of Cfh mRNA in the mouse outer retina. Immunohistochemistry (IHC) was used to localize Cfh protein expression, and western blots were used to characterize CFH antibodies used for IHC. Results Cfh and Cfhr2 transcripts were detected in the mouse RPE/choroid using qPCR, while Cfhr1, Cfhr3, and Cfhrc (Gm4788) were not detected. ISH showed abundant Cfh mRNA in the RPE of all mouse strains (C57BL/6, BALB/c, 129/Sv) tested, with the exception of the Cfh−/− eye. Surprisingly, the Cfh protein was detected by immunohistochemistry in photoreceptors rather than in RPE cells. The specificity of the CFH antibodies was tested by western blotting. Our CFH antibodies recognized purified mouse Cfh protein, serum Cfh protein in wild-type C57BL/6, BALB/c, and 129/Sv, and showed an absence of the Cfh protein in the serum of Cfh−/− mice. Greatly reduced Cfh protein immunohistological signals in the Cfh−/− eyes also supported the specificity of the Cfh protein distribution results. Conclusions Only Cfh and Cfhr2 genes are expressed in the mouse outer retina. Only Cfh mRNA was detected in the RPE, but no protein. We hypothesize that the steady-state concentration of Cfh protein is low in the cells due to secretion, and therefore is below the detection level for IHC. PMID:25684976

Functional insights from the distribution and role of homopeptide repeat-containing proteins

PubMed Central

Faux, Noel G.; Bottomley, Stephen P.; Lesk, Arthur M.; Irving, James A.; Morrison, John R.; de la Banda, Maria Garcia; Whisstock, James C.

2005-01-01

Expansion of “low complex” repeats of amino acids such as glutamine (Poly-Q) is associated with protein misfolding and the development of degenerative diseases such as Huntington's disease. The mechanism by which such regions promote misfolding remains controversial, the function of many repeat-containing proteins (RCPs) remains obscure, and the role (if any) of repeat regions remains to be determined. Here, a Web-accessible database of RCPs is presented. The distribution and evolution of RCPs that contain homopeptide repeats tracts are considered, and the existence of functional patterns investigated. Generally, it is found that while polyamino acid repeats are extremely rare in prokaryotes, several eukaryote putative homologs of prokaryote RCP—involved in important housekeeping processes—retain the repetitive region, suggesting an ancient origin for certain repeats. Within eukarya, the most common uninterrupted amino acid repeats are glutamine, asparagines, and alanine. Interestingly, while poly-Q repeats are found in vertebrates and nonvertebrates, poly-N repeats are only common in more primitive nonvertebrate organisms, such as insects and nematodes. We have assigned function to eukaryote RCPs using Online Mendelian Inheritance in Man (OMIM), the Human Reference Protein Database (HRPD), FlyBase, and Wormpep. Prokaryote RCPs were annotated using BLASTp searches and Gene Ontology. These data reveal that the majority of RCPs are involved in processes that require the assembly of large, multiprotein complexes, such as transcription and signaling. PMID:15805494

Update of the ATTRACT force field for the prediction of protein-protein binding affinity.

PubMed

Chéron, Jean-Baptiste; Zacharias, Martin; Antonczak, Serge; Fiorucci, Sébastien

2017-06-05

Determining the protein-protein interactions is still a major challenge for molecular biology. Docking protocols has come of age in predicting the structure of macromolecular complexes. However, they still lack accuracy to estimate the binding affinities, the thermodynamic quantity that drives the formation of a complex. Here, an updated version of the protein-protein ATTRACT force field aiming at predicting experimental binding affinities is reported. It has been designed on a dataset of 218 protein-protein complexes. The correlation between the experimental and predicted affinities reaches 0.6, outperforming most of the available protocols. Focusing on a subset of rigid and flexible complexes, the performance raises to 0.76 and 0.69, respectively. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Are Charge-State Distributions a Reliable Tool Describing Molecular Ensembles of Intrinsically Disordered Proteins by Native MS?

NASA Astrophysics Data System (ADS)

Natalello, Antonino; Santambrogio, Carlo; Grandori, Rita

2017-01-01

Native mass spectrometry (MS) has become a central tool of structural proteomics, but its applicability to the peculiar class of intrinsically disordered proteins (IDPs) is still object of debate. IDPs lack an ordered tridimensional structure and are characterized by high conformational plasticity. Since they represent valuable targets for cancer and neurodegeneration research, there is an urgent need of methodological advances for description of the conformational ensembles populated by these proteins in solution. However, structural rearrangements during electrospray-ionization (ESI) or after the transfer to the gas phase could affect data obtained by native ESI-MS. In particular, charge-state distributions (CSDs) are affected by protein conformation inside ESI droplets, while ion mobility (IM) reflects protein conformation in the gas phase. This review focuses on the available evidence relating IDP solution ensembles with CSDs, trying to summarize cases of apparent consistency or discrepancy. The protein-specificity of ionization patterns and their responses to ligands and buffer conditions suggests that CSDs are imprinted to protein structural features also in the case of IDPs. Nevertheless, it seems that these proteins are more easily affected by electrospray conditions, leading in some cases to rearrangements of the conformational ensembles.

Are Charge-State Distributions a Reliable Tool Describing Molecular Ensembles of Intrinsically Disordered Proteins by Native MS?

PubMed

Natalello, Antonino; Santambrogio, Carlo; Grandori, Rita

2017-01-01

Native mass spectrometry (MS) has become a central tool of structural proteomics, but its applicability to the peculiar class of intrinsically disordered proteins (IDPs) is still object of debate. IDPs lack an ordered tridimensional structure and are characterized by high conformational plasticity. Since they represent valuable targets for cancer and neurodegeneration research, there is an urgent need of methodological advances for description of the conformational ensembles populated by these proteins in solution. However, structural rearrangements during electrospray-ionization (ESI) or after the transfer to the gas phase could affect data obtained by native ESI-MS. In particular, charge-state distributions (CSDs) are affected by protein conformation inside ESI droplets, while ion mobility (IM) reflects protein conformation in the gas phase. This review focuses on the available evidence relating IDP solution ensembles with CSDs, trying to summarize cases of apparent consistency or discrepancy. The protein-specificity of ionization patterns and their responses to ligands and buffer conditions suggests that CSDs are imprinted to protein structural features also in the case of IDPs. Nevertheless, it seems that these proteins are more easily affected by electrospray conditions, leading in some cases to rearrangements of the conformational ensembles. Graphical Abstract ᅟ.

The Technique of Changing the Drive Method of Micro Step Drive and Sensorless Drive for Hybrid Stepping Motor

NASA Astrophysics Data System (ADS)

Yoneda, Makoto; Dohmeki, Hideo

The position control system with the advantage large torque, low vibration, and high resolution can be obtained by the constant current micro step drive applied to hybrid stepping motor. However loss is large, in order not to be concerned with load torque but to control current uniformly. As the one technique of a position control system in which high efficiency is realizable, the same sensorless control as a permanent magnet motor is effective. But, it was the purpose that the control method proposed until now controls speed. Then, this paper proposed changing the drive method of micro step drive and sensorless drive. The change of the drive method was verified from the simulation and the experiment. On no load, it was checked not producing change of a large speed at the time of a change by making electrical angle and carrying out zero reset of the integrator. On load, it was checked that a large speed change arose. The proposed system could change drive method by setting up the initial value of an integrator using the estimated result, without producing speed change. With this technique, the low loss position control system, which employed the advantage of the hybrid stepping motor, has been built.

Distribution and cluster analysis of predicted intrinsically disordered protein Pfam domains

PubMed Central

Williams, Robert W; Xue, Bin; Uversky, Vladimir N; Dunker, A Keith

2013-01-01

The Pfam database groups regions of proteins by how well hidden Markov models (HMMs) can be trained to recognize similarities among them. Conservation pressure is probably in play here. The Pfam seed training set includes sequence and structure information, being drawn largely from the PDB. A long standing hypothesis among intrinsically disordered protein (IDP) investigators has held that conservation pressures are also at play in the evolution of different kinds of intrinsic disorder, but we find that predicted intrinsic disorder (PID) is not always conserved across Pfam domains. Here we analyze distributions and clusters of PID regions in 193024 members of the version 23.0 Pfam seed database. To include the maximum information available for proteins that remain unfolded in solution, we employ the 10 linearly independent Kidera factors1–3 for the amino acids, combined with PONDR4 predictions of disorder tendency, to transform the sequences of these Pfam members into an 11 column matrix where the number of rows is the length of each Pfam region. Cluster analyses of the set of all regions, including those that are folded, show 6 groupings of domains. Cluster analyses of domains with mean VSL2b scores greater than 0.5 (half predicted disorder or more) show at least 3 separated groups. It is hypothesized that grouping sets into shorter sequences with more uniform length will reveal more information about intrinsic disorder and lead to more finely structured and perhaps more accurate predictions. HMMs could be trained to include this information. PMID:28516017

Engineering Globular Protein Vesicles through Tunable Self-Assembly of Recombinant Fusion Proteins

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

Jang, Yeongseon; Choi, Won Tae; Heller, William T.

Vesicles assembled from folded, globular proteins have potential for functions different from traditional lipid or polymeric vesicles. However, they also present challenges in understanding the assembly process and controlling vesicle properties. From detailed investigation of the assembly behavior of recombinant fusion proteins, this work reports a simple strategy to engineer protein vesicles containing functional, globular domains. This is achieved through tunable self-assembly of recombinant globular fusion proteins containing leucine zippers and elastin-like polypeptides. The fusion proteins form complexes in solution via high affinity binding of the zippers, and transition through dynamic coacervates to stable hollow vesicles upon warming. The thermalmore » driving force, which can be tuned by protein concentration or temperature, controls both vesicle size and whether vesicles are single or bi-layered. Lastly, these results provide critical information to engineer globular protein vesicles via self-assembly with desired size and membrane structure.« less

Engineering Globular Protein Vesicles through Tunable Self-Assembly of Recombinant Fusion Proteins

DOE PAGES

Jang, Yeongseon; Choi, Won Tae; Heller, William T.; ...

2017-07-27

Vesicles assembled from folded, globular proteins have potential for functions different from traditional lipid or polymeric vesicles. However, they also present challenges in understanding the assembly process and controlling vesicle properties. From detailed investigation of the assembly behavior of recombinant fusion proteins, this work reports a simple strategy to engineer protein vesicles containing functional, globular domains. This is achieved through tunable self-assembly of recombinant globular fusion proteins containing leucine zippers and elastin-like polypeptides. The fusion proteins form complexes in solution via high affinity binding of the zippers, and transition through dynamic coacervates to stable hollow vesicles upon warming. The thermalmore » driving force, which can be tuned by protein concentration or temperature, controls both vesicle size and whether vesicles are single or bi-layered. Lastly, these results provide critical information to engineer globular protein vesicles via self-assembly with desired size and membrane structure.« less

Vision-related fitness to drive mobility scooters: A practical driving test.

PubMed

Cordes, Christina; Heutink, Joost; Tucha, Oliver M; Brookhuis, Karel A; Brouwer, Wiebo H; Melis-Dankers, Bart J M

2017-03-06

To investigate practical fitness to drive mobility scooters, comparing visually impaired participants with healthy controls. Between-subjects design. Forty-six visually impaired (13 with very low visual acuity, 10 with low visual acuity, 11 with peripheral field defects, 12 with multiple visual impairment) and 35 normal-sighted controls. Participants completed a practical mobility scooter test-drive, which was recorded on video. Two independent occupational therapists specialized in orientation and mobility evaluated the videos systematically. Approximately 90% of the visually impaired participants passed the driving test. On average, participants with visual impairments performed worse than normal-sighted controls, but were judged sufficiently safe. In particular, difficulties were observed in participants with peripheral visual field defects and those with a combination of low visual acuity and visual field defects. People with visual impairment are, in practice, fit to drive mobility scooters; thus visual impairment on its own should not be viewed as a determinant of safety to drive mobility scooters. However, special attention should be paid to individuals with visual field defects with or without a combined low visual acuity. The use of an individual practical fitness-to-drive test is advised.

Dynamically correlated mutations drive human Influenza A evolution.

PubMed

Tria, F; Pompei, S; Loreto, V

2013-01-01

Human Influenza A virus undergoes recurrent changes in the hemagglutinin (HA) surface protein, primarily involved in the human antibody recognition. Relevant antigenic changes, enabling the virus to evade host immune response, have been recognized to occur in parallel to multiple mutations at antigenic sites in HA. Yet, the role of correlated mutations (epistasis) in driving the molecular evolution of the virus still represents a challenging puzzle. Further, though circulation at a global geographic level is key for the survival of Influenza A, its role in shaping the viral phylodynamics remains largely unexplored. Here we show, through a sequence based epidemiological model, that epistatic effects between amino acids substitutions, coupled with a reservoir that mimics worldwide circulating viruses, are key determinants that drive human Influenza A evolution. Our approach explains all the up-to-date observations characterizing the evolution of H3N2 subtype, including phylogenetic properties, nucleotide fixation patterns, and composition of antigenic clusters.

Taxonomic distribution and origins of the extended LHC (light-harvesting complex) antenna protein superfamily

PubMed Central

2010-01-01

Background The extended light-harvesting complex (LHC) protein superfamily is a centerpiece of eukaryotic photosynthesis, comprising the LHC family and several families involved in photoprotection, like the LHC-like and the photosystem II subunit S (PSBS). The evolution of this complex superfamily has long remained elusive, partially due to previously missing families. Results In this study we present a meticulous search for LHC-like sequences in public genome and expressed sequence tag databases covering twelve representative photosynthetic eukaryotes from the three primary lineages of plants (Plantae): glaucophytes, red algae and green plants (Viridiplantae). By introducing a coherent classification of the different protein families based on both, hidden Markov model analyses and structural predictions, numerous new LHC-like sequences were identified and several new families were described, including the red lineage chlorophyll a/b-binding-like protein (RedCAP) family from red algae and diatoms. The test of alternative topologies of sequences of the highly conserved chlorophyll-binding core structure of LHC and PSBS proteins significantly supports the independent origins of LHC and PSBS families via two unrelated internal gene duplication events. This result was confirmed by the application of cluster likelihood mapping. Conclusions The independent evolution of LHC and PSBS families is supported by strong phylogenetic evidence. In addition, a possible origin of LHC and PSBS families from different homologous members of the stress-enhanced protein subfamily, a diverse and anciently paralogous group of two-helix proteins, seems likely. The new hypothesis for the evolution of the extended LHC protein superfamily proposed here is in agreement with the character evolution analysis that incorporates the distribution of families and subfamilies across taxonomic lineages. Intriguingly, stress-enhanced proteins, which are universally found in the genomes of green plants

Parkinson's disease and driving ability

PubMed Central

Singh, Rajiv; Pentland, Brian; Hunter, John; Provan, Frances

2007-01-01

Objectives To explore the driving problems associated with Parkinson's disease (PD) and to ascertain whether any clinical features or tests predict driver safety. Methods The driving ability of 154 individuals with PD referred to a driving assessment centre was determined by a combination of clinical tests, reaction times on a test rig and an in‐car driving test. Results The majority of cases (104, 66%) were able to continue driving although 46 individuals required an automatic transmission and 10 others needed car modifications. Ability to drive was predicted by the severity of physical disease, age, presence of other associated medical conditions, particularly dementia, duration of disease, brake reaction, time on a test rig and score on a driving test (all p<0.001). The level of drug treatment and the length of driving history were not correlated. Discriminant analysis revealed that the most important features in distinguishing safety to drive were severe physical disease (Hoehn and Yahr stage 3), reaction time, moderate disease associated with another medical condition and high score on car testing. Conclusions Most individuals with PD are safe to drive, although many benefit from car modifications or from using an automatic transmission. A combination of clinical tests and in‐car driving assessment will establish safety to drive, and a number of clinical correlates can be shown to predict the likely outcome and may assist in the decision process. This is the largest series of consecutive patients seen at a driving assessment centre reported to date, and the first to devise a scoring system for on‐road driving assessment. PMID:17178820

High-risk driving attitudes and everyday driving violations of car and racing enthusiasts in Ontario, Canada.

PubMed

Yildirim-Yenier, Zümrüt; Vingilis, Evelyn; Wiesenthal, David L; Mann, Robert E; Seeley, Jane

2015-01-01

Attitudes and individual difference variables of car and racing enthusiasts regarding high-risk behaviors of street racing and stunt driving have recently been investigated. Positive attitudes toward high-risk driving, personality variables such as driver thrill seeking, and other self-reported risky driving acts were associated with these behaviors. However, probable relationships among high-risk driving tendencies, everyday driving behaviors, and negative road safety outcomes have remained largely unexamined. This study aimed to investigate the associations among car and racing enthusiasts' high-risk driving attitudes, self-reported everyday driving violations (i.e., ordinary and aggressive violations), and self-reported negative outcomes (i.e., collisions and driving offense citations). A web-based survey was conducted with members and visitors of car club and racing websites in Ontario, Canada. Data were obtained from 366 participants. The questionnaire included 4 attitude measures-(1) attitudes toward new penalties for Ontario's Street Racers, Stunt and Aggressive Drivers Legislation; (2) attitudes toward new offenses of stunt driving under the same legislation; (3) general attitudes toward street racing and stunt driving; (4) comparison of street racing with other risky driving behaviors-self-reported driving violations (i.e., ordinary and aggressive violations); self-reported collisions and offense citations; and background and driving questions (e.g., age, driving frequency). Results revealed that attitudes toward stunt driving offenses negatively and general attitudes toward street racing and stunt driving positively predicted ordinary violations, which, in turn, predicted offense citations. Moreover, general attitudes toward street racing and stunt driving positively predicted aggressive violations, which, in turn, predicted offense citations. The findings indicate that positive high-risk driving attitudes may be transferring to driving violations in

Bullied no more:when and how DNA shoves proteins around

PubMed Central

Pettitt, B. Montgomery; Sumners, De Witt L.; Harris, Sarah A.; Zechiedrich, Lynn

2016-01-01

The predominant protein-centric perspective in protein–DNA-binding studies assumes that the protein drives the interaction. Research focuses on protein structural motifs, electrostatic surfaces and contact potentials, while DNA is often ignored as a passive polymer to be manipulated. Recent studies of DNA topology, the supercoiling, knotting, and linking of the helices, have shown that DNA has the capability to be an active participant in its transactions. DNA topology-induced structural and geometric changes can drive, or at least strongly influence, the interactions between protein and DNA. Deformations of the B-form structure arise from both the considerable elastic energy arising from supercoiling and from the electrostatic energy. Here, we discuss how these energies are harnessed for topology-driven, sequence-specific deformations that can allow DNA to direct its own metabolism. PMID:22850561

Coagulation factor Xa drives tumor cells into apoptosis through BH3-only protein Bim up-regulation

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

Borensztajn, Keren S.; Bijlsma, Maarten F.; Groot, Angelique P.

2007-07-15

Coagulation Factor (F)Xa is a serine protease that plays a crucial role during blood coagulation by converting prothrombin into active thrombin. Recently, however, it emerged that besides this role in coagulation, FXa induces intracellular signaling leading to different cellular effects. Here, we show that coagulation factor (F)Xa drives tumor cells of epithelial origin, but not endothelial cells or monocytes, into apoptosis, whereas it even enhances fibroblast survival. FXa signals through the protease activated receptor (PAR)-1 to activate extracellular-signal regulated kinase (ERK) 1/2 and p38. This activation is associated with phosphorylation of the transcription factor CREB, and in tumor cells withmore » up-regulation of the BH3-only pro-apoptotic protein Bim, leading to caspase-3 cleavage, the main hallmark of apoptosis. Transfection of tumor cells with dominant negative forms of CREB or siRNA for either PAR-1, Bim, ERK1 and/or p38 inhibited the pro-apoptotic effect of FXa. In fibroblasts, FXa-induced PAR-1 activation leads to down-regulation of Bim and pre-treatment with PAR-1 or Bim siRNA abolishes proliferation. We thus provide evidence that beyond its role in blood coagulation, FXa plays a key role in cellular processes in which Bim is the central player in determining cell survival.« less

N-terminal-mediated oligomerization of DnaA drives the occupancy-dependent rejuvenation of the protein on the membrane.

PubMed

Aranovich, Alexander; Braier-Marcovitz, Shani; Ansbacher, Esti; Granek, Rony; Parola, Abraham H; Fishov, Itzhak

2015-08-13

DnaA, the initiator of chromosome replication in most known eubacteria species, is activated once per cell division cycle. Its overall activity cycle is driven by ATP hydrolysis and ADP-ATP exchange. The latter can be promoted by binding to specific sequences on the chromosome and/or to acidic phospholipids in the membrane. We have previously shown that the transition into an active form (rejuvenation) is strongly co-operative with respect to DnaA membrane occupancy. Only at low membrane occupancy is DnaA reactivation efficiently catalysed by the acidic phospholipids. The present study was aimed at unravelling the molecular mechanism underlying the occupancy-dependent DnaA rejuvenation. We found that truncation of the DnaA N-terminal completely abolishes the co-operative transformation between the high and low occupancy states (I and II respectively) without affecting the membrane binding. The environmentally sensitive fluorophore specifically attached to the N-terminal cysteines of DnaA reported on occupancy-correlated changes in its vicinity. Cross-linking of DnaA with a short homobifunctional reagent revealed that state II of the protein on the membrane corresponds to a distinct oligomeric form of DnaA. The kinetic transition of DnaA on the membrane surface is described in the present study by a generalized 2D condensation phase transition model, confirming the existence of two states of DnaA on the membrane and pointing to the possibility that membrane protein density serves as an on-off switch in vivo. We conclude that the DnaA conformation attained at low surface density drives its N-terminal-mediated oligomerization, which is presumably a pre-requisite for facilitated nt exchange. © 2015 Authors.

Control rod drive

DOEpatents

Hawke, Basil C.

1986-01-01

A control rod drive uses gravitational forces to insert one or more control rods upwardly into a reactor core from beneath the reactor core under emergency conditions. The preferred control rod drive includes a vertically movable weight and a mechanism operatively associating the weight with the control rod so that downward movement of the weight is translated into upward movement of the control rod. The preferred control rod drive further includes an electric motor for driving the control rods under normal conditions, an electrically actuated clutch which automatically disengages the motor during a power failure and a decelerator for bringing the control rod to a controlled stop when it is inserted under emergency conditions into a reactor core.

Driving range estimation for electric vehicles based on driving condition identification and forecast

NASA Astrophysics Data System (ADS)

Pan, Chaofeng; Dai, Wei; Chen, Liao; Chen, Long; Wang, Limei

2017-10-01

With the impact of serious environmental pollution in our cities combined with the ongoing depletion of oil resources, electric vehicles are becoming highly favored as means of transport. Not only for the advantage of low noise, but for their high energy efficiency and zero pollution. The Power battery is used as the energy source of electric vehicles. However, it does currently still have a few shortcomings, noticeably the low energy density, with high costs and short cycle life results in limited mileage compared with conventional passenger vehicles. There is great difference in vehicle energy consumption rate under different environment and driving conditions. Estimation error of current driving range is relatively large due to without considering the effects of environmental temperature and driving conditions. The development of a driving range estimation method will have a great impact on the electric vehicles. A new driving range estimation model based on the combination of driving cycle identification and prediction is proposed and investigated. This model can effectively eliminate mileage errors and has good convergence with added robustness. Initially the identification of the driving cycle is based on Kernel Principal Component feature parameters and fuzzy C referring to clustering algorithm. Secondly, a fuzzy rule between the characteristic parameters and energy consumption is established under MATLAB/Simulink environment. Furthermore the Markov algorithm and BP(Back Propagation) neural network method is utilized to predict the future driving conditions to improve the accuracy of the remaining range estimation. Finally, driving range estimation method is carried out under the ECE 15 condition by using the rotary drum test bench, and the experimental results are compared with the estimation results. Results now show that the proposed driving range estimation method can not only estimate the remaining mileage, but also eliminate the fluctuation of the

Medications and impaired driving.

PubMed

Hetland, Amanda; Carr, David B

2014-04-01

To describe the association of specific medication classes with driving outcomes and provide clinical recommendations. The MEDLINE and EMBASE databases were searched for articles published from January 1973 to June 2013 on classes of medications associated with driving impairment. The search included outcome terms such as automobile driving, motor vehicle crash, driving simulator, and road tests. Only English-language articles that contained findings from observational or interventional designs with ≥ 10 participants were included in this review. Cross-sectional studies, case series, and case reports were excluded. Driving is an important task and activity for the majority of adults. Some commonly prescribed medications have been associated with driving impairment measured by road performance, driving simulation, and/or motor vehicle crashes. This review of 30 studies identified findings with barbiturates, benzodiazepines, hypnotics, antidepressants, opioid and nonsteroidal analgesics, anticonvulsants, antipsychotics, antiparkinsonian agents, skeletal muscle relaxants, antihistamines, anticholinergic medications, and hypoglycemic agents. Additional studies of medication impact on sedation, sleep latency, and psychomotor function, as well as the role of alcohol, are also discussed. Psychotropic agents and those with central nervous system side effects were associated with measures of impaired driving performance. It is difficult to determine if such associations are actually a result of medication use or the medical diagnosis itself. Regardless, clinicians should be aware of the increased risk of impaired driving with specific classes of medications, educate their patients, and/or consider safer alternatives.

Observational study of the extent of driving while suspended for alcohol-impaired driving

DOT National Transportation Integrated Search

2002-09-01

A study was undertaken to determine the proportion of first-time alcohol-impaired driving offenders who drive while suspended and the circumstances and motivations for driving. Systematic, unobtrusive observations were conducted by surveillance profe...

DISTRIBUTED RC NETWORKS WITH RATIONAL TRANSFER FUNCTIONS,

DTIC Science & Technology

A distributed RC circuit analogous to a continuously tapped transmission line can be made to have a rational short-circuit transfer admittance and...one rational shortcircuit driving-point admittance. A subcircuit of the same structure has a rational open circuit transfer impedance and one rational ...open circuit driving-point impedance. Hence, rational transfer functions may be obtained while considering either generator impedance or load

Correspondence between Simulator and On-Road Drive Performance: Implications for Assessment of Driving Safety.

PubMed

Aksan, Nazan; Hacker, Sarah D; Sager, Lauren; Dawson, Jeffrey; Anderson, Steven; Rizzo, Matthew

2016-03-01

Forty-two younger (Mean age = 35) and 37 older drivers (Mean age = 77) completed four similar simulated drives. In addition, 32 younger and 30 older drivers completed a standard on-road drive in an instrumented vehicle. Performance in the simulated drives was evaluated using both electronic drive data and video-review of errors. Safety errors during the on-road drive were evaluated by a certified driving instructor blind to simulator performance, using state Department of Transportation criteria. We examined the degree of convergence in performance across the two platforms on various driving tasks including lane change, lane keeping, speed control, stopping, turns, and overall performance. Differences based on age group indicated a pattern of strong relative validity for simulator measures. However, relative rank-order in specific metrics of performance suggested a pattern of moderate relative validity. The findings have implications for the use of simulators in assessments of driving safety as well as its use in training and/or rehabilitation settings.

Correspondence between Simulator and On-Road Drive Performance: Implications for Assessment of Driving Safety

PubMed Central

Aksan, Nazan; Hacker, Sarah D.; Sager, Lauren; Dawson, Jeffrey; Anderson, Steven; Rizzo, Matthew

2017-01-01

Forty-two younger (Mean age = 35) and 37 older drivers (Mean age = 77) completed four similar simulated drives. In addition, 32 younger and 30 older drivers completed a standard on-road drive in an instrumented vehicle. Performance in the simulated drives was evaluated using both electronic drive data and video-review of errors. Safety errors during the on-road drive were evaluated by a certified driving instructor blind to simulator performance, using state Department of Transportation criteria. We examined the degree of convergence in performance across the two platforms on various driving tasks including lane change, lane keeping, speed control, stopping, turns, and overall performance. Differences based on age group indicated a pattern of strong relative validity for simulator measures. However, relative rank-order in specific metrics of performance suggested a pattern of moderate relative validity. The findings have implications for the use of simulators in assessments of driving safety as well as its use in training and/or rehabilitation settings. PMID:28649572

Vehicle ownership and other predictors of teenagers risky driving behavior: Evidence from a naturalistic driving study.

PubMed

Gershon, Pnina; Ehsani, Johnathon; Zhu, Chunming; O'Brien, Fearghal; Klauer, Sheila; Dingus, Tom; Simons-Morton, Bruce

2018-06-08

Risky driving behavior may contribute to the high crash risk among teenage drivers. The current naturalistic driving study assessed predictors for teenagers' kinematic risky driving (KRD) behavior and the interdependencies between them. The private vehicles of 81 novice teenage drivers were equipped with data acquisition system that recorded driving kinematics, miles driven, and video recordings of the driver, passengers and the driving environment. Psychosocial measures were collected using questionnaires administered at licensure. Poisson regression analyses and model selection were used to assess factors associated with teens' risky driving behavior and the interactions between them. Driving own vs shared vehicle, driving during the day vs at night, and driving alone vs with passengers were significantly associated with higher KRD rates (Incidence rate ratios (IRRs) of 1.60, 1.41, and 1.28, respectively). Teenagers reporting higher vs lower levels of parental trust had significantly lower KRD rates (IRR = 0.58). KRD rates were 88% higher among teenagers driving with a passenger in their own vehicle compared to teenagers driving with a passenger in a shared vehicle. Similarly, KRD rates during the day were 74% higher among teenagers driving their own vehicle compared to those driving a shared vehicle. Novice teenagers' risky driving behavior varied according to driver attributes and contextual aspects of the driving environment. As such, examining teenagers' risky driving behavior should take into account multiple contributing factors and their interactions. The variability in risky driving according to the driving context can inform the development of targeted interventions to reduce the crash risk of novice teenage drivers. Copyright © 2018 Elsevier Ltd. All rights reserved.

Electrostatic contributions drive the interaction between Staphylococcus aureus protein Efb-C and its complement target C3d.

PubMed

Haspel, Nurit; Ricklin, Daniel; Geisbrecht, Brian V; Kavraki, Lydia E; Lambris, John D

2008-11-01

The C3-inhibitory domain of Staphylococcus aureus extracellular fibrinogen-binding protein (Efb-C) defines a novel three-helix bundle motif that regulates complement activation. Previous crystallographic studies of Efb-C bound to its cognate subdomain of human C3 (C3d) identified Arg-131 and Asn-138 of Efb-C as key residues for its activity. In order to characterize more completely the physical and chemical driving forces behind this important interaction, we employed in this study a combination of structural, biophysical, and computational methods to analyze the interaction of C3d with Efb-C and the single-point mutants R131A and N138A. Our results show that while these mutations do not drastically affect the structure of the Efb-C/C3d recognition complex, they have significant adverse effects on both the thermodynamic and kinetic profiles of the resulting complexes. We also characterized other key interactions along the Efb-C/C3d binding interface and found an intricate network of salt bridges and hydrogen bonds that anchor Efb-C to C3d, resulting in its potent complement inhibitory properties.

The impact of continuous driving time and rest time on commercial drivers' driving performance and recovery.

PubMed

Wang, Lianzhen; Pei, Yulong

2014-09-01

This real road driving study was conducted to investigate the effects of driving time and rest time on the driving performance and recovery of commercial coach drivers. Thirty-three commercial coach drivers participated in the study, and were divided into three groups according to driving time: (a) 2 h, (b) 3 h, and (c) 4 h. The Stanford Sleepiness Scale (SSS) was used to assess the subjective fatigue level of the drivers. One-way ANOVA was employed to analyze the variation in driving performance. The statistical analysis revealed that driving time had a significant effect on the subjective fatigue and driving performance measures among the three groups. After 2 h of driving, both the subjective fatigue and driving performance measures began to deteriorate. After 4 h of driving, all of the driving performance indicators changed significantly except for depth perception. A certain amount of rest time eliminated the negative effects of fatigue. A 15-minute rest allowed drivers to recover from a two-hour driving task. This needed to be prolonged to 30 min for driving tasks of 3 to 4 h of continuous driving. Drivers' attention, reactions, operating ability, and perceptions are all affected in turn after over 2 h of continuous driving. Drivers should take a certain amount of rest to recover from the fatigue effects before they continue driving. Copyright © 2014 National Safety Council and Elsevier Ltd. All rights reserved.

Finite element analysis of ROPS for mechanical driving dump truck cab

NASA Astrophysics Data System (ADS)

Wang, Yong; Xie, Heping; Fang, Yuanbin; Feng, Handui; Dong, Lei

2018-02-01

For roll-over protective structures (ROPS) in a mechanical driving dump truck cab, it simulates the lateral, vertical and longitudinal loads of ROPS. It obtains stress and deformation of the cab that occurs to roll. For the relative weak position of ROPS in the cab, the structure of the cab is improved and verified according to the ISO 3164: 1995. The results show that the established finite element model can effectively predict the deformation and stress distribution of ROPS, and optimize the weak structure of the cab, which has important guiding significance for structural design of the cab and ROPS optimization of the mechanical driving dump truck cab.

Effects of decades of physical driving on body movement and motion sickness during virtual driving

PubMed Central

Chang, Chih-Hui; Chen, Fu-Chen; Zeng, Wei-Jhong

2017-01-01

We investigated relations between experience driving physical automobiles and motion sickness during the driving of virtual automobiles. Middle-aged individuals drove a virtual automobile in a driving video game. Drivers were individuals who had possessed a driver’s license for approximately 30 years, and who drove regularly, while non-drivers were individuals who had never held a driver’s license, or who had not driven for more than 15 years. During virtual driving, we monitored movement of the head and torso. During virtual driving, drivers became motion sick more rapidly than non-drivers, but the incidence and severity of motion sickness did not differ as a function of driving experience. Patterns of movement during virtual driving differed as a function of driving experience. Separately, movement differed between participants who later became motion sick and those who did not. Most importantly, physical driving experience influenced patterns of postural activity that preceded motion sickness during virtual driving. The results are consistent with the postural instability theory of motion sickness, and help to illuminate relations between the control of physical and virtual vehicles. PMID:29121059

Age Distribution of Lunar Impact-Melt Rocks in Apollo Drive-Tube 68001/2

NASA Technical Reports Server (NTRS)

Curran, N. M.; Bower, D. M.; Frasl, B.; Cohen, B. A.

2018-01-01

Apollo 16 double-drive tube 68001 /68002 provides impact and volcanic materials along a depth of approximately 60 cm in five compositional distinct units. 68001 /2 offers the potential to study distinct populations of impact melts with depth to understand how 'gardening' affects these samples. We will use unbiased major-element chemistry, mineralogy, and age to understand the impact history of Apollo 16 landing site. The study demonstrates the techniques that landed missions require to identify lithologies of interest (e.g., impact melts).

Msp1 Is a Membrane Protein Dislocase for Tail-Anchored Proteins.

PubMed

Wohlever, Matthew L; Mateja, Agnieszka; McGilvray, Philip T; Day, Kasey J; Keenan, Robert J

2017-07-20

Mislocalized tail-anchored (TA) proteins of the outer mitochondrial membrane are cleared by a newly identified quality control pathway involving the conserved eukaryotic protein Msp1 (ATAD1 in humans). Msp1 is a transmembrane AAA-ATPase, but its role in TA protein clearance is not known. Here, using purified components reconstituted into proteoliposomes, we show that Msp1 is both necessary and sufficient to drive the ATP-dependent extraction of TA proteins from the membrane. A crystal structure of the Msp1 cytosolic region modeled into a ring hexamer suggests that active Msp1 contains a conserved membrane-facing surface adjacent to a central pore. Structure-guided mutagenesis of the pore residues shows that they are critical for TA protein extraction in vitro and for functional complementation of an msp1 deletion in yeast. Together, these data provide a molecular framework for Msp1-dependent extraction of mislocalized TA proteins from the outer mitochondrial membrane. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of protein conformational motions in the native form and non-uniform distribution of electrostatic interaction sites on interfacial water

NASA Astrophysics Data System (ADS)

Pal, Somedatta; Bandyopadhyay, Sanjoy

2013-07-01

Protein-water interactions and their influence on surrounding water is a long-standing problem. Despite its importance, the origin of differential water behavior at the protein surface is still elusive. We have performed molecular simulations of the protein barstar in aqueous medium. Efforts have been made to explore how the conformational motions of the protein segments in the native form and the heterogeneous electrostatic interactions with the polar and charged groups of the protein affect the interfacial water properties. The calculations reveal that reduced dimension of the hydration layer on freezing the protein's degrees of freedom does not modify the heterogeneous water distributions around the protein. However, turning off the protein-water electrostatic contribution leads to non-preferential near-uniform water arrangements at the surface. It is further shown that with protein-water electrostatic interactions turned on, the local structuring of water molecules around the segments are correlated with their degree of exposure to the solvent.

Driving competences and neuropsychological factors associated to driving counseling in multiple sclerosis.

PubMed

Badenes, Dolors; Garolera, Maite; Casas, Laura; Cejudo-Bolivar, Juan Carlos; de Francisco, Jorge; Zaragoza, Silvia; Calzado, Noemi; Aguilar, Miquel

2014-05-01

Multiple Sclerosis (MS) significantly impacts daily living activities, including car driving. To investigate driving difficulties experienced with MS, we compared 50 MS patients with minor or moderate disability and 50 healthy controls (HC) using computerized driving tests (the ASDE driver test and the Useful Field of View (UFOV) test) and neuropsychological tests. Inclusion criteria included being active drivers. We evaluated whether cognitive deterioration in MS is associated with the results of driving tests by comparing MS patients without cognitive deterioration with HC. The results indicated that the MS patients performed worse than the HCs in attention, information processing, working memory and visuomotor coordination tasks. Furthermore, MS patients with cognitive impairments experienced more difficulties in the driving tests than did the non-impaired MS patients. Motor dysfunction associated with MS also played an important role in this activity. The results of this study suggest that MS should be assessed carefully and that special emphasis should be placed on visuomotor coordination and executive functions because patients with minor motor disability and subtle cognitive impairments can pass measures predictive of driving safety.

[Driving ability and fitness to drive in people with diabetes mellitus].

PubMed

Seeger, Rolf; Lehmann, Roger

2011-05-01

Chronic sequelae of diabetes that could potentially affect driving include the following: visual retinopathy with associated impaired visual acuity, loss of peripheral vision and poor dark adaptation; neuropathy that may affect lower limb functions needed for safe driving; and acute events, including transient cognitive dysfunction and loss of consciousness related to hypo- or hyperglycemia. Hyperglycemia does not suddenly incapacitate drivers, however its occurrence often leads to tiredness, blurred vision, decreased visual acuity and adjustment of treatment which may precipitate hypoglycaemia. The side effects of acute hypoglycemia are of particular concern, as they include slowing of both cognitive and motor functions. Hypoglycemia while driving ist the most important complication in persons treated with insulin, sulfonylureas or glinides. They can be prevented, however, by frequent measuring blood glucose before and every 60 to 90 minutes during driving, by keeping sugary snacks (carbohydrates) in the vehicle, and by taking carbohydrates in case of glucose levels below 5 mmol/l. For patients, who are treated with insulin and sulfonylureas/glinides, it is of utmost importance fort the treating physician to frequently talk about successful strategies for preventing hypoglycemias, and thus accidents, while driving. People with diabetes treated with insulin, sulfonylureas or glinides are nor allowed to drive a bus, taxi, or truck (commercial driving). Under special circumstances (evalution and treatment by a diabetologist/endocrinolgist, avoidance of hypoglycemias for three months, and frequent glucose measurements) an exception to this rule can be granted for truck and cab drivers (after a thorough licensing examination).

Effects of distributions of energy of transfer rates on spectral hole burning in photosynthetic pigment-protein complexes

NASA Astrophysics Data System (ADS)

Ahmouda, Somaya

To perform photosynthesis, plants, algae and bacteria possess well organized and closely coupled photosynthetic pigment-protein complexes. Information on energy transfer in photosynthetic complexes is important to understand their functioning and possibly to design new and improved photovoltaic devices. The information on energy transfer processes contained in the narrow zero-phonon lines at low temperatures is hidden under the inhomogeneous broadening. Thus, it has been proven difficult to analyze the spectroscopic properties of these complexes in sufficient detail by conventional spectroscopy methods. In this context the high resolution spectroscopy techniques such as Spectral Hole Burning are powerful tools designed to get around the inhomogeneous broadening. Spectral Hole Burning involves selective excitation by a laser which removes molecules with the zero-phonon transitions resonant with this laser. This thesis focuses on the effects of the distributions of the energy transfer rates (homogeneous line widths) on the evolution of spectral holes. These distributions are a consequence of the static disorder in the photosynthetic pigment-protein complexes. The qualitative effects of different types of the line width distributions on the evolution of spectral holes have been and explored by numerical simulations, an example of analysis of the original experimental data has been presented as well.

Entropic forces drive self-organization and membrane fusion by SNARE proteins

PubMed Central

Stratton, Benjamin S.; Warner, Jason M.; Rothman, James E.; O’Shaughnessy, Ben

2017-01-01

SNARE proteins are the core of the cell’s fusion machinery and mediate virtually all known intracellular membrane fusion reactions on which exocytosis and trafficking depend. Fusion is catalyzed when vesicle-associated v-SNAREs form trans-SNARE complexes (“SNAREpins”) with target membrane-associated t-SNAREs, a zippering-like process releasing ∼65 kT per SNAREpin. Fusion requires several SNAREpins, but how they cooperate is unknown and reports of the number required vary widely. To capture the collective behavior on the long timescales of fusion, we developed a highly coarse-grained model that retains key biophysical SNARE properties such as the zippering energy landscape and the surface charge distribution. In simulations the ∼65-kT zippering energy was almost entirely dissipated, with fully assembled SNARE motifs but uncomplexed linker domains. The SNAREpins self-organized into a circular cluster at the fusion site, driven by entropic forces that originate in steric–electrostatic interactions among SNAREpins and membranes. Cooperative entropic forces expanded the cluster and pulled the membranes together at the center point with high force. We find that there is no critical number of SNAREs required for fusion, but instead the fusion rate increases rapidly with the number of SNAREpins due to increasing entropic forces. We hypothesize that this principle finds physiological use to boost fusion rates to meet the demanding timescales of neurotransmission, exploiting the large number of v-SNAREs available in synaptic vesicles. Once in an unfettered cluster, we estimate ≥15 SNAREpins are required for fusion within the ∼1-ms timescale of neurotransmitter release. PMID:28490503

Observation of Giant Conductance Fluctuations in a Protein

PubMed Central

Zhang, Bintian; Song, Weisi; Pang, Pei; Zhao, Yanan; Zhang, Peiming; Csabai, István; Vattay, Gábor; Lindsay, Stuart

2017-01-01

Proteins are insulating molecular solids, yet even those containing easily reduced or oxidized centers can have single-molecule electronic conductances that are too large to account for with conventional transport theories. Here, we report the observation of remarkably high electronic conductance states in an electrochemically-inactive protein, the ~200 kD αVβ3 extracelluar domain of human integrin. Large current pulses (up to nA) were observed for long durations (many ms, corresponding to many pC of charge transfer) at large gap (>5nm) distances in an STM when the protein was bound specifically by a small peptide ligand attached to the electrodes. The effect is greatly reduced when a homologous, weakly-binding protein (α4β1) is used as a control. In order to overcome the limitations of the STM, the time- and voltage-dependence of the conductance were further explored using a fixed-gap (5 nm) tunneling junction device that was small enough to trap a single protein molecule at any one time. Transitions to a high conductance (~ nS) state were observed, the protein being “on” for times from ms to tenths of a second. The high-conductance states only occur above ~ 100mV applied bias, and thus are not an equilibrium property of the protein. Nanoamp two-level signals indicate the specific capture of a single molecule in an electrode gap functionalized with the ligand. This offers a new approach to label-free electronic detection of single protein molecules. Electronic structure calculations yield a distribution of energy level spacings that is consistent with a recently proposed quantum-critical state for proteins, in which small fluctuations can drive transitions between localized and band-like electronic states. PMID:29552645

Observation of giant conductance fluctuations in a protein

NASA Astrophysics Data System (ADS)

Zhang, Bintian; Song, Weisi; Pang, Pei; Zhao, Yanan; Zhang, Peiming; Csabai, István; Vattay, Gábor; Lindsay, Stuart

2017-12-01

Proteins are insulating molecular solids, yet even those containing easily reduced or oxidized centers can have single-molecule electronic conductances that are too large to account for with conventional transport theories. Here, we report the observation of remarkably high electronic conductance states in an electrochemically inactive protein, the ∼200 kD α V β 3 extracellular domain of human integrin. Large current pulses (up to nA) were observed for long durations (many ms, corresponding to many pC of charge transfer) at large gap (>5 nm) distances in an STM when the protein was bound specifically by a small peptide ligand attached to the electrodes. The effect is greatly reduced when a homologous, weakly binding protein (α 4 β 1) is used as a control. In order to overcome the limitations of the STM, the time- and voltage-dependence of the conductance were further explored using a fixed-gap (5 nm) tunneling junction device that was small enough to trap a single protein molecule at any one time. Transitions to a high conductance (∼nS) state were observed, the protein being ‘on’ for times from ms to tenths of a second. The high-conductance states only occur above ∼100 mV applied bias, and thus are not an equilibrium property of the protein. Nanoamp two-level signals indicate the specific capture of a single molecule in an electrode gap functionalized with the ligand. This offers a new approach to label-free electronic detection of single protein molecules. Electronic structure calculations yield a distribution of energy level spacings that is consistent with a recently proposed quantum-critical state for proteins, in which small fluctuations can drive transitions between localized and band-like electronic states.

Expression and distribution of the duck enteritis virus UL51 protein in experimentally infected ducks.

PubMed

Shen, Chanjuan; Cheng, Anchun; Wang, Mingshu; Xu, Chao; Jia, Renyong; Chen, Xiaoyue; Zhu, Dekang; Luo, Qihui; Cui, Hengmin; Zhou, Yi; Wang, Yin; Xu, Zhiwen; Chen, Zhengli; Wang, Xiaoyu

2010-06-01

To determine the expression and distribution of tegument proteins encoded by duck enteritis virus (DEV) UL51 gene in tissues of experimentally infected ducks, for the first time, an immunoperoxidase staining method to detect UL51 protein (UL51p) in paraffin-embedded tissues is reported. A rabbit anti-UL51 polyclonal serum, raised against a recombinant 6-His-UL51 fusion protein expressed in Escherichia coli, was prepared, purified, and used as primary antibodies. Fifty-eight 30-day-old DEV-free ducks were intramuscularly inoculated with the pathogenic DEV CHv strain as infection group, and two ducks were selected as preinfection group. The tissues were collected at sequential time points between 2 and 480 hr postinoculation (PI) and prepared for immunoperoxidase staining. DEV UL51p was first found in the spleen and liver at 8 hr PI; in the bursa of Fabricius and thymus at 12 hr PI; in the Harders glands, esophagus, small intestine (including the duodenum, jejunum, and ileum), and large intestine (including the caecum and rectum) at 24 hr PI; in the glandularis ventriculus at 48 hr PI; and in the pancreas, cerebrum, kidney, lung, and myocardium at 72 hr PI. Throughout the infection process, the UL51p was not seen in the muscle. Furthermore, the intensity of positive staining of DEV UL51p antigen in various tissues increased sharply from 8 to 96 hr PI, peaked during 120-144 hr PI, and then decreased steadily from 216 to 480 hr PI, suggesting that the expressional levels of DEV UL51p in systemic organs have a close correlation with the progression of duck virus enteritis (DVE) disease. A number of DEV UL51p was distributed in the bursa of Fabricius, thymus, spleen, liver, esophagus, small intestine, and large intestine of DEV-infected ducks, whereas less DEV UL51p was distributed in the Harders glands, glandularis ventriculus, cerebrum, kidney, lung, pancreas, and myocardium of DEV-infected ducks. Moreover, DEV UL51p can be expressed in the cytoplasm of various types

Gene duplication and fragment recombination drive functional diversification of a superfamily of cytoplasmic effectors in Phytophthora sojae.

PubMed

Shen, Danyu; Liu, Tingli; Ye, Wenwu; Liu, Li; Liu, Peihan; Wu, Yuren; Wang, Yuanchao; Dou, Daolong

2013-01-01

Phytophthora and other oomycetes secrete a large number of putative host cytoplasmic effectors with conserved FLAK motifs following signal peptides, termed crinkling and necrosis inducing proteins (CRN), or Crinkler. Here, we first investigated the evolutionary patterns and mechanisms of CRN effectors in Phytophthora sojae and compared them to two other Phytophthora species. The genes encoding CRN effectors could be divided into 45 orthologous gene groups (OGG), and most OGGs unequally distributed in the three species, in which each underwent large number of gene gains or losses, indicating that the CRN genes expanded after species evolution in Phytophthora and evolved through pathoadaptation. The 134 expanded genes in P. sojae encoded family proteins including 82 functional genes and expressed at higher levels while the other 68 genes encoding orphan proteins were less expressed and contained 50 pseudogenes. Furthermore, we demonstrated that most expanded genes underwent gene duplication or/and fragment recombination. Three different mechanisms that drove gene duplication or recombination were identified. Finally, the expanded CRN effectors exhibited varying pathogenic functions, including induction of programmed cell death (PCD) and suppression of PCD through PAMP-triggered immunity or/and effector-triggered immunity. Overall, these results suggest that gene duplication and fragment recombination may be two mechanisms that drive the expansion and neofunctionalization of the CRN family in P. sojae, which aids in understanding the roles of CRN effectors within each oomycete pathogen.

In Patients With Cirrhosis, Driving Simulator Performance Is Associated With Real-life Driving.

PubMed

Lauridsen, Mette M; Thacker, Leroy R; White, Melanie B; Unser, Ariel; Sterling, Richard K; Stravitz, Richard T; Matherly, Scott; Puri, Puneet; Sanyal, Arun J; Gavis, Edith A; Luketic, Velimir; Siddiqui, Muhammad S; Heuman, Douglas M; Fuchs, Michael; Bajaj, Jasmohan S

2016-05-01

Minimal hepatic encephalopathy (MHE) has been linked to higher real-life rates of automobile crashes and poor performance in driving simulation studies, but the link between driving simulator performance and real-life automobile crashes has not been clearly established. Furthermore, not all patients with MHE are unsafe drivers, but it is unclear how to distinguish them from unsafe drivers. We investigated the link between performance on driving simulators and real-life automobile accidents and traffic violations. We also aimed to identify features of unsafe drivers with cirrhosis and evaluated changes in simulated driving skills and MHE status after 1 year. We performed a study of outpatients with cirrhosis (n = 205; median 55 years old; median model for end-stage liver disease score, 9.5; none with overt hepatic encephalopathy or alcohol or illicit drug use within previous 6 months) seen at the Virginia Commonwealth University and McGuire Veterans Administration Medical Center, from November 2008 through April 2014. All participants were given paper-pencil tests to diagnose MHE (98 had MHE; 48%), and 163 patients completed a standardized driving simulation. Data were collected on traffic violations and automobile accidents from the Virginia Department of Motor Vehicles and from participants' self-assessments when they entered the study, and from 73 participants 1 year later. Participants also completed a questionnaire about alcohol use and cessation patterns. The driving simulator measured crashes, run-time, road center and edge excursions, and illegal turns during navigation; before and after each driving simulation session, patients were asked to rate their overall driving skills. Drivers were classified as safe or unsafe based on crashes and violations reported on official driving records; simulation results were compared with real-life driving records. Multivariable regression analyses of real-life crashes and violations was performed using data on

Thrill and adventure seeking in risky driving at work: The moderating role of safety climate.

PubMed

Wishart, Darren; Somoray, Klaire; Evenhuis, Amanda

2017-12-01

Introduction Within many industrialized countries, the leading cause of worker fatalities and serious injuries can be attributed to road trauma. In non-occupational research, high levels of sensation seeking personality, and specifically thrill and adventure seeking, have been associated with risky driving behaviors. In work driving literature, high organizational safety climate has been associated with reduced risky driving in work drivers. However, the extent that factors such as safety climate and thrill seeking interact in regard to work driving safety remains unclear, and the current research examined this interaction. Methods A total of 1,011 work drivers from four organizations participated in the research. Surveys were distributed online and hardcopies were sent via mail. The survey included measures of thrill and adventure seeking, safety climate and work-related driving behaviors, as well as questions relating to participant demographics and information about their work driving. Results The results demonstrated that safety climate significantly moderated the effect of thrill and adventure seeking trait on driving errors, driving violations, and driving while fatigued. Conclusion These results suggest that the development of a strong safety climate has the potential to improve work driving safety outcomes by reducing the impact of particular personality traits such as thrill seeking within an organizational context. Practical application To improve work driving safety, organizations and management need to develop strategies to encourage and foster positive work driving safety climate, particularly within work settings that may attract thrill and adventure seeking employees. Copyright © 2017. Published by Elsevier Ltd.

Free energy decomposition of protein-protein interactions.

PubMed

Noskov, S Y; Lim, C

2001-08-01

A free energy decomposition scheme has been developed and tested on antibody-antigen and protease-inhibitor binding for which accurate experimental structures were available for both free and bound proteins. Using the x-ray coordinates of the free and bound proteins, the absolute binding free energy was computed assuming additivity of three well-defined, physical processes: desolvation of the x-ray structures, isomerization of the x-ray conformation to a nearby local minimum in the gas-phase, and subsequent noncovalent complex formation in the gas phase. This free energy scheme, together with the Generalized Born model for computing the electrostatic solvation free energy, yielded binding free energies in remarkable agreement with experimental data. Two assumptions commonly used in theoretical treatments; viz., the rigid-binding approximation (which assumes no conformational change upon complexation) and the neglect of vdW interactions, were found to yield large errors in the binding free energy. Protein-protein vdW and electrostatic interactions between complementary surfaces over a relatively large area (1400--1700 A(2)) were found to drive antibody-antigen and protease-inhibitor binding.

Origins of pressure-induced protein transitions.

PubMed

Chalikian, Tigran V; Macgregor, Robert B

2009-12-18

The molecular mechanisms underlying pressure-induced protein denaturation can be analyzed based on the pressure-dependent differences in the apparent volume occupied by amino acids inside the protein and when they are exposed to water in an unfolded conformation. We present here an analysis for the peptide group and the 20 naturally occurring amino acid side chains based on volumetric parameters for the amino acids in the interior of the native state, the micelle-like interior of the pressure-induced denatured state, and the unfolded conformation modeled by N-acetyl amino acid amides. The transfer of peptide groups from the protein interior to water becomes increasingly favorable as pressure increases. Thus, solvation of peptide groups represents a major driving force in pressure-induced protein denaturation. Polar side chains do not appear to exhibit significant pressure-dependent changes in their preference for the protein interior or solvent. The transfer of nonpolar side chains from the protein interior to water becomes more unfavorable as pressure increases. We conclude that a sizeable population of nonpolar side chains remains buried inside a solvent-inaccessible core of the pressure-induced denatured state. At elevated pressures, this core may become packed almost as tightly as the interior of the native state. The presence and partial disappearance of large intraglobular voids is another driving force facilitating pressure-induced denaturation of individual proteins. Our data also have implications for the kinetics of protein folding and shed light on the nature of the folding transition state ensemble.

A Laboratory Demonstration Illustrating Bioseparations Using Colorful Proteins

ERIC Educational Resources Information Center

Cohen, Theodore M.; Rohs, Amanda E.; Lefebvre, Brian G.

2008-01-01

A simple in class laboratory illustrating the principles of ion exchange chromatography as a bioseparation technique is described. A protein's isoelectric point as a driving force for ion exchange chromatography is easily demonstrated by using combinations of proteins with natural color or fluorescence, such as DsRed2, enhanced green fluorescent…

Empirical null estimation using zero-inflated discrete mixture distributions and its application to protein domain data.

PubMed

Gauran, Iris Ivy M; Park, Junyong; Lim, Johan; Park, DoHwan; Zylstra, John; Peterson, Thomas; Kann, Maricel; Spouge, John L

2017-09-22

In recent mutation studies, analyses based on protein domain positions are gaining popularity over gene-centric approaches since the latter have limitations in considering the functional context that the position of the mutation provides. This presents a large-scale simultaneous inference problem, with hundreds of hypothesis tests to consider at the same time. This article aims to select significant mutation counts while controlling a given level of Type I error via False Discovery Rate (FDR) procedures. One main assumption is that the mutation counts follow a zero-inflated model in order to account for the true zeros in the count model and the excess zeros. The class of models considered is the Zero-inflated Generalized Poisson (ZIGP) distribution. Furthermore, we assumed that there exists a cut-off value such that smaller counts than this value are generated from the null distribution. We present several data-dependent methods to determine the cut-off value. We also consider a two-stage procedure based on screening process so that the number of mutations exceeding a certain value should be considered as significant mutations. Simulated and protein domain data sets are used to illustrate this procedure in estimation of the empirical null using a mixture of discrete distributions. Overall, while maintaining control of the FDR, the proposed two-stage testing procedure has superior empirical power. 2017 The Authors. Biometrics published by Wiley Periodicals, Inc. on behalf of International Biometric Society This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Modeling Driving Performance Using In-Vehicle Speech Data From a Naturalistic Driving Study.

PubMed

Kuo, Jonny; Charlton, Judith L; Koppel, Sjaan; Rudin-Brown, Christina M; Cross, Suzanne

2016-09-01

We aimed to (a) describe the development and application of an automated approach for processing in-vehicle speech data from a naturalistic driving study (NDS), (b) examine the influence of child passenger presence on driving performance, and (c) model this relationship using in-vehicle speech data. Parent drivers frequently engage in child-related secondary behaviors, but the impact on driving performance is unknown. Applying automated speech-processing techniques to NDS audio data would facilitate the analysis of in-vehicle driver-child interactions and their influence on driving performance. Speech activity detection and speaker diarization algorithms were applied to audio data from a Melbourne-based NDS involving 42 families. Multilevel models were developed to evaluate the effect of speech activity and the presence of child passengers on driving performance. Speech activity was significantly associated with velocity and steering angle variability. Child passenger presence alone was not associated with changes in driving performance. However, speech activity in the presence of two child passengers was associated with the most variability in driving performance. The effects of in-vehicle speech on driving performance in the presence of child passengers appear to be heterogeneous, and multiple factors may need to be considered in evaluating their impact. This goal can potentially be achieved within large-scale NDS through the automated processing of observational data, including speech. Speech-processing algorithms enable new perspectives on driving performance to be gained from existing NDS data, and variables that were once labor-intensive to process can be readily utilized in future research. © 2016, Human Factors and Ergonomics Society.

Continued driving and time to transition to nondriver status through error-specific driving restrictions.

PubMed

Freund, Barbara; Petrakos, Davithoula

2008-01-01

We developed driving restrictions that are linked to specific driving errors, allowing cognitively impaired individuals to continue to independently meet mobility needs while minimizing risk to themselves and others. The purpose of this project was to evaluate the efficacy and duration expectancy of these restrictions in promoting safe continued driving. We followed 47 drivers age 60 years and older for 18 months, evaluating driving performance at 6-month intervals. Results demonstrated restricted drivers had safety profiles similar to safe drivers and gained additional driving time to transition to nondrivers.

i3Drive, a 3D interactive driving simulator.

PubMed

Ambroz, Miha; Prebil, Ivan

2010-01-01

i3Drive, a wheeled-vehicle simulator, can accurately simulate vehicles of various configurations with up to eight wheels in real time on a desktop PC. It presents the vehicle dynamics as an interactive animation in a virtual 3D environment. The application is fully GUI-controlled, giving users an easy overview of the simulation parameters and letting them adjust those parameters interactively. It models all relevant vehicle systems, including the mechanical models of the suspension, power train, and braking and steering systems. The simulation results generally correspond well with actual measurements, making the system useful for studying vehicle performance in various driving scenarios. i3Drive is thus a worthy complement to other, more complex tools for vehicle-dynamics simulation and analysis.

Surface Mediated Protein Disaggregation

NASA Astrophysics Data System (ADS)

Radhakrishna, Mithun; Kumar, Sanat K.

2014-03-01

Preventing protein aggregation is of both biological and industrial importance. Biologically these aggregates are known to cause amyloid type diseases like Alzheimer's and Parkinson's disease. Protein aggregation leads to reduced activity of the enzymes in industrial applications. Inter-protein interactions between the hydrophobic residues of the protein are known to be the major driving force for protein aggregation. In the current paper we show how surface chemistry and curvature can be tuned to mitigate these inter-protein interactions. Our results calculated in the framework of the Hydrophobic-Polar (HP) lattice model show that, inter-protein interactions can be drastically reduced by increasing the surface hydrophobicity to a critical value corresponding to the adsorption transition of the protein. At this value of surface hydrophobicity, proteins lose inter-protein contacts to gain surface contacts and thus the surface helps in reducing the inter-protein interactions. Further, we show that the adsorption of the proteins inside hydrophobic pores of optimal sizes are most efficient both in reducing inter-protein contacts and simultaneously retaining most of the native-contacts due to strong protein-surface interactions coupled with stabilization due to the confinement. Department of Energy (Grant No DE-FG02-11ER46811).

Does early training improve driving skills of young novice French drivers?

PubMed

Freydier, Chloé; Berthelon, Catherine; Bastien-Toniazzo, Mireille

2016-11-01

The aim of this research was to study drivers' performances and divided attention depending on their initial training. The performances of young novice drivers who received early training, traditionally trained drivers and more experienced drivers were compared during a dual task consisting of a simulated car-following task and a number' parity judgment task. It was expected that, due to their limited driving experience, the young novice drivers would have more difficulty in adequately distributing their attention between the two tasks. Poorer performances by novice drivers than experienced drivers were therefore expected. The results indicate that traditionally trained drivers had more difficulties in speed regulation and maintaining their position in the lane than drivers with early training and experienced drivers. Performance impairment linked to driving inexperience was also found in the secondary task. The results were interpreted regarding the attentional resources involved in driving with a secondary task and supported the positive effects of French early training. Copyright © 2016 Elsevier Ltd. All rights reserved.

Among High School Seniors, Driving After Marijuana Use Surpasses Drunk Driving

MedlinePlus

... Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the Brain ... Brain College-Age and Young Adults Comorbidity Criminal Justice Drug Testing Drugged Driving Evidence-Based Practices Genetics ...

Turbulent unmixing: how marine turbulence drives patchy distributions of motile phytoplankton

NASA Astrophysics Data System (ADS)

Durham, William; Climent, Eric; Barry, Michael; de Lillo, Filippo; Boffetta, Guido; Cencini, Massimo; Stocker, Roman

2013-11-01

Centimeter-scale patchiness in the distribution of phytoplankton increases the efficacy of many important ecological interactions in the marine food web. We show that turbulent fluid motion, usually synonymous with mixing, instead triggers intense small-scale patchiness in the distribution of motile phytoplankton. We use a suite of experiments, direct numerical simulations of turbulence, and analytical tools to show that turbulent shear and acceleration directs the motility of cells towards well-defined regions of flow, increasing local cell concentrations more than ten fold. This motility-driven `unmixing' offers an explanation for why motile cells are often more patchily distributed than non-motile cells and provides a mechanistic framework to understand how turbulence, whose strength varies profoundly in marine environments, impacts ocean productivity.

Model Predictive Control Based Motion Drive Algorithm for a Driving Simulator

NASA Astrophysics Data System (ADS)

Rehmatullah, Faizan

In this research, we develop a model predictive control based motion drive algorithm for the driving simulator at Toronto Rehabilitation Institute. Motion drive algorithms exploit the limitations of the human vestibular system to formulate a perception of motion within the constrained workspace of a simulator. In the absence of visual cues, the human perception system is unable to distinguish between acceleration and the force of gravity. The motion drive algorithm determines control inputs to displace the simulator platform, and by using the resulting inertial forces and angular rates, creates the perception of motion. By using model predictive control, we can optimize the use of simulator workspace for every maneuver while simulating the vehicle perception. With the ability to handle nonlinear constraints, the model predictive control allows us to incorporate workspace limitations.

A drive through Web 2.0: an exploration of driving safety promotion on Facebook™.

PubMed

Apatu, Emma J I; Alperin, Melissa; Miner, Kathleen R; Wiljer, David

2013-01-01

This study explored Facebook™ to capture the prevalence of driving safety promotion user groups, obtain user demographic information, to understand if Facebook™ user groups influence reported driving behaviors, and to gather a sense of perceived effectiveness of Facebook™ for driving safety promotion targeted to young adults. In total, 96 driving safety Facebook™ groups (DSFGs) were identified with a total of 33,368 members, 168 administrators, 156 officers, 1,598 wall posts representing 12 countries. A total of 85 individuals participated in the survey. Demographic findings of this study suggest that driving safety promotion can be targeted to young and older adults. Respondents' ages ranged from 18 to 66 years. A total of 62% of respondents aged ≤ 24 years and 57.8% of respondents aged ≥ 25 years reported changing their driving-related behaviors as a result of reading information on the DSFGs to which they belonged. A higher proportion of respondents ≥ 25 years were significantly more likely to report Facebook™ and YouTube™ as an effective technology for driving safety promotion. This preliminary study indicates that DSFGs may be effective tools for driving safety promotion among young adults. More research is needed to understand the cognition of Facebook™ users as it relates to adopting safe driving behavior. The findings from this study present descriptive data to guide public health practitioners for future health promotion activities on Facebook™.

Self-driving carsickness.

PubMed

Diels, Cyriel; Bos, Jelte E

2016-03-01

This paper discusses the predicted increase in the occurrence and severity of motion sickness in self-driving cars. Self-driving cars have the potential to lead to significant benefits. From the driver's perspective, the direct benefits of this technology are considered increased comfort and productivity. However, we here show that the envisaged scenarios all lead to an increased risk of motion sickness. As such, the benefits this technology is assumed to bring may not be capitalised on, in particular by those already susceptible to motion sickness. This can negatively affect user acceptance and uptake and, in turn, limit the potential socioeconomic benefits that this emerging technology may provide. Following a discussion on the causes of motion sickness in the context of self-driving cars, we present guidelines to steer the design and development of automated vehicle technologies. The aim is to limit or avoid the impact of motion sickness and ultimately promote the uptake of self-driving cars. Attention is also given to less well known consequences of motion sickness, in particular negative aftereffects such as postural instability, and detrimental effects on task performance and how this may impact the use and design of self-driving cars. We conclude that basic perceptual mechanisms need to be considered in the design process whereby self-driving cars cannot simply be thought of as living rooms, offices, or entertainment venues on wheels. Copyright © 2015 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Sequential Dependencies in Driving

ERIC Educational Resources Information Center

Doshi, Anup; Tran, Cuong; Wilder, Matthew H.; Mozer, Michael C.; Trivedi, Mohan M.

2012-01-01

The effect of recent experience on current behavior has been studied extensively in simple laboratory tasks. We explore the nature of sequential effects in the more naturalistic setting of automobile driving. Driving is a safety-critical task in which delayed response times may have severe consequences. Using a realistic driving simulator, we find…

Driving automation forward : human factors for limited-ability autonomous driving systems.

DOT National Transportation Integrated Search

2010-01-01

Over the past 100 years, there has been a : steady progression of innovations that : enhance the driving experience, in particular : the continuing trend toward automating more : driving tasks. Human Factors for Limited-Ability : Autonomous Drivin...

Spatial Characteristics and Driving Factors of Provincial Wastewater Discharge in China

PubMed Central

Chen, Kunlun; Liu, Xiaoqiong; Ding, Lei; Huang, Gengzhi; Li, Zhigang

2016-01-01

Based on the increasing pressure on the water environment, this study aims to clarify the overall status of wastewater discharge in China, including the spatio-temporal distribution characteristics of wastewater discharge and its driving factors, so as to provide reference for developing “emission reduction” strategies in China and discuss regional sustainable development and resources environment policies. We utilized the Exploratory Spatial Data Analysis (ESDA) method to analyze the characteristics of the spatio-temporal distribution of the total wastewater discharge among 31 provinces in China from 2002 to 2013. Then, we discussed about the driving factors, affected the wastewater discharge through the Logarithmic Mean Divisia Index (LMDI) method and classified those driving factors. Results indicate that: (1) the total wastewater discharge steadily increased, based on the social economic development, with an average growth rate of 5.3% per year; the domestic wastewater discharge is the main source of total wastewater discharge, and the amount of domestic wastewater discharge is larger than the industrial wastewater discharge. There are many spatial differences of wastewater discharge among provinces via the ESDA method. For example, provinces with high wastewater discharge are mainly the developed coastal provinces such as Jiangsu Province and Guangdong Province. Provinces and their surrounding areas with low wastewater discharge are mainly the undeveloped ones in Northwest China; (2) The dominant factors affecting wastewater discharge are the economy and technological advance; The secondary one is the efficiency of resource utilization, which brings about the unstable effect; population plays a less important role in wastewater discharge. The dominant driving factors affecting wastewater discharge among 31 provinces are divided into three types, including two-factor dominant type, three-factor leading type and four-factor antagonistic type. In addition

Spatial Characteristics and Driving Factors of Provincial Wastewater Discharge in China.

PubMed

Chen, Kunlun; Liu, Xiaoqiong; Ding, Lei; Huang, Gengzhi; Li, Zhigang

2016-12-09

Based on the increasing pressure on the water environment, this study aims to clarify the overall status of wastewater discharge in China, including the spatio-temporal distribution characteristics of wastewater discharge and its driving factors, so as to provide reference for developing "emission reduction" strategies in China and discuss regional sustainable development and resources environment policies. We utilized the Exploratory Spatial Data Analysis (ESDA) method to analyze the characteristics of the spatio-temporal distribution of the total wastewater discharge among 31 provinces in China from 2002 to 2013. Then, we discussed about the driving factors, affected the wastewater discharge through the Logarithmic Mean Divisia Index (LMDI) method and classified those driving factors. Results indicate that: (1) the total wastewater discharge steadily increased, based on the social economic development, with an average growth rate of 5.3% per year; the domestic wastewater discharge is the main source of total wastewater discharge, and the amount of domestic wastewater discharge is larger than the industrial wastewater discharge. There are many spatial differences of wastewater discharge among provinces via the ESDA method. For example, provinces with high wastewater discharge are mainly the developed coastal provinces such as Jiangsu Province and Guangdong Province. Provinces and their surrounding areas with low wastewater discharge are mainly the undeveloped ones in Northwest China; (2) The dominant factors affecting wastewater discharge are the economy and technological advance; The secondary one is the efficiency of resource utilization, which brings about the unstable effect; population plays a less important role in wastewater discharge. The dominant driving factors affecting wastewater discharge among 31 provinces are divided into three types, including two-factor dominant type, three-factor leading type and four-factor antagonistic type. In addition, the

Integrative omics analysis reveals differentially distributed proteins in dimorphic euspermatozoa of the squid, Loligo bleekeri.

PubMed

Yoshida, Masa-aki; Yamada, Lixy; Ochi, Hiroe; Iwata, Yoko; Tamura-Nakano, Miwa; Sawada, Hitoshi; Sauer, Warwick H H; Ogura, Atsushi; Hirohashi, Noritaka

2014-08-01

In the coastal squid Loligo bleekeri, each male produces one of two types of fertilization-competent spermatozoa (eusperm) that exhibit morphological and behavioral differences. Large "consort" males produce short-tailed spermatozoa that display free-swimming behavior when ejaculated into seawater. Small "sneaker" males, on the other hand, produce long-tailed spermatozoa that exhibit a self-swarming trait after ejaculation. To understand the molecular basis for adaptive traits employed by alternative male mating tactics, we performed the transcriptome deep sequencing (RNA-seq) and proteome analyses to search for differences in testicular mRNAs and sperm proteins, respectively. From mature male testes we identified a total of 236,455 contigs (FPKM ≧1) where 3789 and 2789 were preferentially (≧10-fold) expressed in consort and sneaker testes, respectively. A proteomic analysis detected 4302 proteins in the mature sperm as post-translational products. A strongly biased (≧10-fold) distribution occurred in 55 consort proteins and 61 sneaker proteins. There was no clear mRNA-protein correlation, making a ballpark estimate impossible for not only overall protein abundance but also the degree of biased sperm type expressed in the spermatozoa. A family encoding dynein heavy chain gene, however, was found to be biased towards sneakers, whereas many enzymes involving energy metabolism were heavily biased towards consort spermatozoa. The difference in flagellar length matched exactly the different amount of tubulins. From these results we hypothesize that discrete differential traits in dimorphic eusperm arose from a series of innovative alterations in the intracellular components of spermatozoa. Copyright © 2014 Elsevier Inc. All rights reserved.

Driving performance at lateral system limits during partially automated driving.

PubMed

Naujoks, Frederik; Purucker, Christian; Wiedemann, Katharina; Neukum, Alexandra; Wolter, Stefan; Steiger, Reid

2017-11-01

This study investigated driver performance during system limits of partially automated driving. Using a motion-based driving simulator, drivers encountered different situations in which a partially automated vehicle could no longer safely keep the lateral guidance. Drivers were distracted by a non-driving related task on a touch display or driving without an additional secondary task. While driving in partially automated mode drivers could either take their hands off the steering wheel for only a short period of time (10s, so-called 'Hands-on' variant) or for an extended period of time (120s, so-called 'Hands-off' variant). When the system limit was reached (e.g., when entering a work zone with temporary lines), the lateral vehicle control by the automation was suddenly discontinued and a take-over request was issued to the drivers. Regardless of the hands-off interval and the availability of a secondary task, all drivers managed the transition to manual driving safely. No lane exceedances were observed and the situations were rated as 'harmless' by the drivers. The lack of difference between the hands-off intervals can be partly attributed to the fact that most of the drivers kept contact to the steering wheel, even in the hands-off condition. Although all drivers were able to control the system limits, most of them could not explain why exactly the take-over request was issued. The average helpfulness of the take-over request was rated on an intermediate level. Consequently, providing drivers with information about the reason for a system limit can be recommended. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Test Drive

NASA Technical Reports Server (NTRS)

2004-01-01

This image taken at NASA's Jet Propulsion Laboratory shows engineers rehearsing the sol 133 (June 8, 2004) drive into 'Endurance' crater by NASA's Mars Exploration Rover Opportunity. Engineers and scientists have recreated the martian surface and slope the rover will encounter using a combination of bare and thinly sand-coated rocks, simulated martian 'blueberries' and a platform tilted at a 25-degree angle. The results of this test convinced engineers that the rover was capable of driving up and down a straight slope before it attempted the actual drive on Mars.

Measurements of the driving forces of bio-motors using the fluctuation theorem

PubMed Central

Hayashi, Kumiko; Tanigawara, Mizue; Kishikawa, Jun-ichi

2012-01-01

The fluctuation theorem (FT), which is a recent achievement in non-equilibrium statistical mechanics, has been suggested to be useful for measuring the driving forces of motor proteins. As an example of this application, we performed single-molecule experiments on F1-ATPase, which is a rotary motor protein, in which we measured its rotary torque by taking advantage of FT. Because fluctuation is inherent nature in biological small systems and because FT is a non-destructive force measurement method using fluctuation, it will be applied to a wide range of biological small systems in future. PMID:27857609

Carbohydrate-Aromatic Interactions in Proteins.

PubMed

Hudson, Kieran L; Bartlett, Gail J; Diehl, Roger C; Agirre, Jon; Gallagher, Timothy; Kiessling, Laura L; Woolfson, Derek N

2015-12-09

Protein-carbohydrate interactions play pivotal roles in health and disease. However, defining and manipulating these interactions has been hindered by an incomplete understanding of the underlying fundamental forces. To elucidate common and discriminating features in carbohydrate recognition, we have analyzed quantitatively X-ray crystal structures of proteins with noncovalently bound carbohydrates. Within the carbohydrate-binding pockets, aliphatic hydrophobic residues are disfavored, whereas aromatic side chains are enriched. The greatest preference is for tryptophan with an increased prevalence of 9-fold. Variations in the spatial orientation of amino acids around different monosaccharides indicate specific carbohydrate C-H bonds interact preferentially with aromatic residues. These preferences are consistent with the electronic properties of both the carbohydrate C-H bonds and the aromatic residues. Those carbohydrates that present patches of electropositive saccharide C-H bonds engage more often in CH-π interactions involving electron-rich aromatic partners. These electronic effects are also manifested when carbohydrate-aromatic interactions are monitored in solution: NMR analysis indicates that indole favorably binds to electron-poor C-H bonds of model carbohydrates, and a clear linear free energy relationships with substituted indoles supports the importance of complementary electronic effects in driving protein-carbohydrate interactions. Together, our data indicate that electrostatic and electronic complementarity between carbohydrates and aromatic residues play key roles in driving protein-carbohydrate complexation. Moreover, these weak noncovalent interactions influence which saccharide residues bind to proteins, and how they are positioned within carbohydrate-binding sites.

Adsorption properties of BSA and DsRed proteins deposited on thin SiO2 layers: optically non-absorbing versus absorbing proteins

NASA Astrophysics Data System (ADS)

Scarangella, A.; Soumbo, M.; Villeneuve-Faure, C.; Mlayah, A.; Bonafos, C.; Monje, M.-C.; Roques, C.; Makasheva, K.

2018-03-01

Protein adsorption on solid surfaces is of interest for many industrial and biomedical applications, where it represents the conditioning step for micro-organism adhesion and biofilm formation. To understand the driving forces of such an interaction we focus in this paper on the investigation of the adsorption of bovine serum albumin (BSA) (optically non-absorbing, model protein) and DsRed (optically absorbing, naturally fluorescent protein) on silica surfaces. Specifically, we propose synthesis of thin protein layers by means of dip coating of the dielectric surface in protein solutions with different concentrations (0.01-5.0 g l-1). We employed spectroscopic ellipsometry as the most suitable and non-destructive technique for evaluation of the protein layers’ thickness and optical properties (refractive index and extinction coefficient) after dehydration, using two different optical models, Cauchy for BSA and Lorentz for DsRed. We demonstrate that the thickness, the optical properties and the wettability of the thin protein layers can be finely controlled by proper tuning of the protein concentration in the solution. These results are correlated with the thin layer morphology, investigated by AFM, FTIR and PL analyses. It is shown that the proteins do not undergo denaturation after dehydration on the silica surface. The proteins arrange themselves in a lace-like network for BSA and in a rod-like structure for DsRed to form mono- and multi-layers, due to different mechanisms driving the organization stage.

Distinct Cellular and Subcellular Distributions of G Protein-Coupled Receptor Kinase and Arrestin Isoforms in the Striatum

PubMed Central

Bychkov, Evgeny; Zurkovsky, Lilia; Garret, Mika B.; Ahmed, Mohamed R.; Gurevich, Eugenia V.

2012-01-01

G protein-coupled receptor kinases (GRKs) and arrestins mediate desensitization of G protein-coupled receptors (GPCR). Arrestins also mediate G protein-independent signaling via GPCRs. Since GRK and arrestins demonstrate no strict receptor specificity, their functions in the brain may depend on their cellular complement, expression level, and subcellular targeting. However, cellular expression and subcellular distribution of GRKs and arrestins in the brain is largely unknown. We show that GRK isoforms GRK2 and GRK5 are similarly expressed in direct and indirect pathway neurons in the rat striatum. Arrestin-2 and arrestin-3 are also expressed in neurons of both pathways. Cholinergic interneurons are enriched in GRK2, arrestin-3, and GRK5. Parvalbumin-positive interneurons express more of GRK2 and less of arrestin-2 than medium spiny neurons. The GRK5 subcellular distribution in the human striatal neurons is altered by its phosphorylation: unphosphorylated enzyme preferentially localizes to synaptic membranes, whereas phosphorylated GRK5 is found in plasma membrane and cytosolic fractions. Both GRK isoforms are abundant in the nucleus of human striatal neurons, whereas the proportion of both arrestins in the nucleus was equally low. However, overall higher expression of arrestin-2 yields high enough concentration in the nucleus to mediate nuclear functions. These data suggest cell type- and subcellular compartment-dependent differences in GRK/arrestin-mediated desensitization and signaling. PMID:23139825

Distinct cellular and subcellular distributions of G protein-coupled receptor kinase and arrestin isoforms in the striatum.

PubMed

Bychkov, Evgeny; Zurkovsky, Lilia; Garret, Mika B; Ahmed, Mohamed R; Gurevich, Eugenia V

2012-01-01

G protein-coupled receptor kinases (GRKs) and arrestins mediate desensitization of G protein-coupled receptors (GPCR). Arrestins also mediate G protein-independent signaling via GPCRs. Since GRK and arrestins demonstrate no strict receptor specificity, their functions in the brain may depend on their cellular complement, expression level, and subcellular targeting. However, cellular expression and subcellular distribution of GRKs and arrestins in the brain is largely unknown. We show that GRK isoforms GRK2 and GRK5 are similarly expressed in direct and indirect pathway neurons in the rat striatum. Arrestin-2 and arrestin-3 are also expressed in neurons of both pathways. Cholinergic interneurons are enriched in GRK2, arrestin-3, and GRK5. Parvalbumin-positive interneurons express more of GRK2 and less of arrestin-2 than medium spiny neurons. The GRK5 subcellular distribution in the human striatal neurons is altered by its phosphorylation: unphosphorylated enzyme preferentially localizes to synaptic membranes, whereas phosphorylated GRK5 is found in plasma membrane and cytosolic fractions. Both GRK isoforms are abundant in the nucleus of human striatal neurons, whereas the proportion of both arrestins in the nucleus was equally low. However, overall higher expression of arrestin-2 yields high enough concentration in the nucleus to mediate nuclear functions. These data suggest cell type- and subcellular compartment-dependent differences in GRK/arrestin-mediated desensitization and signaling.

32 CFR 634.14 - Restoration of driving privileges upon acquittal of intoxicated driving.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 4 2010-07-01 2010-07-01 true Restoration of driving privileges upon acquittal of intoxicated driving. 634.14 Section 634.14 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) LAW ENFORCEMENT AND CRIMINAL INVESTIGATIONS MOTOR VEHICLE TRAFFIC SUPERVISION Driving Privileges § 634.14 Restoration...

Determination of The Mechanical Power in Belt Conveyor's Drive System in Industrial Conditions

NASA Astrophysics Data System (ADS)

Król, Robert; Kaszuba, Damian; Kisielewski, Waldemar

2016-10-01

Mechanical power is a value which carries a significant amount of information on the properties of the operating status of the machine analysed. The value of mechanical power reflects the degree of load of the drive system and of the entire machine. It is essential to determine the actual efficiency of the drive system η [%], which is the key parameter of the energy efficiency of the drive system. In the case of a single drive of a belt conveyor the actual efficiency is expressed as the ratio of mechanical output power Pm [W] at the drive pulley shaft to active electrical power drawn by the motor Pe [W]. Furthermore, the knowledge about the mechanical power from all drives of the multiple driven belt conveyor allows for the analysis of load distribution between the drives. In case of belt conveyor, the mechanical power Pm [W] generated by the drive at the drive pulley's shaft is equal to its angular velocity ω [rad / s] multiplied by the torque T [Nm]. The measurement of angular velocity is relatively easy and can be realized with the use of a tachometer or can be determined on the basis of linear velocity of the conveyor belt during belt conveyor's steady state operation. Significantly more difficult to perform in industrial conditions is the measurement of the torque. This is due to the operational conditions of belt conveyors (e.g. dustiness, high humidity, high temperature) and tight assembly of the drive components without the possibility of their disassembly. It makes it difficult or even impossible to measure the torque using a number of the techniques available, causing an individual approach to each object of research. The paper proposes a measurement methodology allowing to determine the mechanical power in belt conveyors drives which are commonly used in underground and surface mining. The paper presents result of the research into mechanical power in belt conveyor's drive carried out in underground mine conditions.

Some distinctive features of zebrafish myogenesis based on unexpected distributions of the muscle cytoskeletal proteins actin, myosin, desmin, alpha-actinin, troponin and titin.

PubMed

Costa, Manoel L; Escaleira, Roberta C; Rodrigues, Viviane B; Manasfi, Muhamed; Mermelstein, Claudia S

2002-08-01

The current myofibrillogenesis model is based mostly on in vitro cell cultures and on avian and mammalian embryos in situ. We followed the expression of actin, myosin, desmin, alpha-actinin, titin, and troponin using immunofluorescence microscopy of zebrafish (Danio rerio) embryos. We could see young mononucleated myoblasts with sharp striations. The striations were positive for all the sarcomeric proteins. Desmin distribution during muscle maturation changes from dispersed aggregates to a perinuclear concentration to striated afterwards. We could not observe desmin-positive, myofibrillar-proteins-negative cells, and we could not find any non-striated distribution of sarcomeric proteins, such as stress fiber-like structures. Some steps, like fusion before striation, seem to be different in the zebrafish when compared with the previously described myogenesis sequences.

A Difficult Journey: Reflections on Driving and Driving Cessation From a Team of Clinical Researchers.

PubMed

Liddle, Jacki; Gustafsson, Louise; Mitchell, Geoffrey; Pachana, Nancy A

2017-02-01

Recognizing the clinical importance and safety and well-being implications for the population, a multidisciplinary team has been researching older drivers and driving cessation issues for more than 15 years. Using empirical approaches, the team has explored quality of life and participation outcomes related to driving and nondriving for older people and has developed interventions to improve outcomes after driving cessation. The team members represent occupational therapists, medical practitioners, and clinical and neuropsychologists. While building the evidence base for driving- and driving cessation-related clinical practice, the researchers have also had first-hand experiences of interruptions to their own or parents' driving; involvement of older family members in road crashes; and provision of support during family members' driving assessment and cessation. This has led to reflection on their understandings and re-evaluation and refocusing of their perspectives in driving cessation research. This work will share the narratives of the authors and note their developing perspectives and foci within research as well as their clinical practice. Personal reflections have indicated the far-reaching implications for older drivers and family members of involvement in road crashes: the potential for interruptions to driving as a time for support and future planning and the conflicting and difficult roles of family members within the driving cessation process. Overall the lived, personal experience of the authors has reinforced the complex nature of driving and changes to driving status for the driver and their support team and the need for further research and support. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Monitoring Protein–Protein Interactions Using Split Synthetic Renilla Luciferase Protein-Fragment-Assisted Complementation

PubMed Central

Paulmurugan, R.; Gambhir, S. S.

2014-01-01

In this study we developed an inducible synthetic renilla luciferase protein-fragment-assisted complementation-based bioluminescence assay to quantitatively measure real time protein–protein interactions in mammalian cells. We identified suitable sites to generate fragments of N and C portions of the protein that yield significant recovered activity through complementation. We validate complementation-based activation of split synthetic renilla luciferase protein driven by the interaction of two strongly interacting proteins, MyoD and Id, in five different cell lines utilizing transient transfection studies. The expression level of the system was also modulated by tumor necrosis factor α through NFκB-promoter/enhancer elements used to drive expression of the N portion of synthetic renilla luciferase reporter gene. This new system should help in studying protein–protein interactions and when used with other split reporters (e.g., split firefly luciferase) should help to monitor different components of an intracellular network. PMID:12705589

Binding of small molecules at interface of protein-protein complex - A newer approach to rational drug design.

PubMed

Gurung, A B; Bhattacharjee, A; Ajmal Ali, M; Al-Hemaid, F; Lee, Joongku

2017-02-01

Protein-protein interaction is a vital process which drives many important physiological processes in the cell and has also been implicated in several diseases. Though the protein-protein interaction network is quite complex but understanding its interacting partners using both in silico as well as molecular biology techniques can provide better insights for targeting such interactions. Targeting protein-protein interaction with small molecules is a challenging task because of druggability issues. Nevertheless, several studies on the kinetics as well as thermodynamic properties of protein-protein interactions have immensely contributed toward better understanding of the affinity of these complexes. But, more recent studies on hot spots and interface residues have opened up new avenues in the drug discovery process. This approach has been used in the design of hot spot based modulators targeting protein-protein interaction with the objective of normalizing such interactions.

Hydrodynamic stability and Ti-tracer distribution in low-adiabat OMEGA direct-drive implosions

NASA Astrophysics Data System (ADS)

Joshi, Tirtha R.

We discuss the hydrodynamic stability of low-adiabat OMEGA direct-drive implosions based on results obtained from simultaneous emission and absorption spectroscopy of a titanium tracer added to the target. The targets were deuterium filled, warm plastic shells of varying thicknesses and filling gas pressures with a submicron Ti-doped tracer layer initially located on the inner surface of the shell. The spectral features from the titanium tracer are observed during the deceleration and stagnation phases of the implosion, and recorded with a time integrated spectrometer (XRS1), streaked crystal spectrometer (SSCA) and three gated, multi-monochromatic X-ray imager (MMI) instruments fielded along quasi-orthogonal lines-of-sight. The time-integrated, streaked and gated data show simultaneous emission and absorption spectral features associated with titanium K-shell line transitions but only the MMI data provides spatially resolved information. The arrays of gated spectrally resolved images recorded with MMI were processed to obtain spatially resolved spectra characteristic of annular contour regions on the image. A multi-zone spectroscopic analysis of the annular spatially resolved spectra permits the extraction of plasma conditions in the core as well as the spatial distribution of tracer atoms. In turn, the titanium atom distribution provides direct evidence of tracer penetration into the core and thus of the hydrodynamic stability of the shell. The observations, timing and analysis indicate that during fuel burning the titanium atoms have migrated deep into the core and thus shell material mixing is likely to impact the rate of nuclear fusion reactions, i.e. burning rate, and the neutron yield of the implosion. We have found that the Ti atom number density decreases towards the center in early deceleration phase, but later in time the trend is just opposite, i.e., it increases towards the center of the implosion core. This is in part a consequence of the convergent

Driving assessment and rehabilitation using a driving simulator in individuals with traumatic brain injury: A scoping review.

PubMed

Imhoff, Sarah; Lavallière, Martin; Teasdale, Normand; Fait, Philippe

2016-06-30

Due to the heterogeneity of the lesion following a traumatic brain injury (TBI) and the complexity of the driving task, driving assessment and rehabilitation in TBI individuals is challenging. Conventional driving assessment (on-road and in-clinic evaluations) has failed demonstrating effectiveness to assess fitness to drive in TBI individuals. We aimed to determine if driving simulators represent an interesting opportunity in assessing and rehabilitating driving skills in TBI individuals. We searched PubMed, CINAHL and Cochrane library databases between 27-02-2014 and 08-04-2014 for articles published since 2000 with the contents of simulator driving assessment and rehabilitation. Out of 488, eight articles with the subject of simulator driving assessment and two with the subject of simulator driving rehabilitation in individuals with TBI were reviewed. Driving simulators represent a promising avenue for the assessment and rehabilitation of driving skills in TBI individuals as it allows control of stimuli in a safe, challenging and ecologically valid environment and offer the opportunity to measure and record driving performance. Additional studies, however, are needed to document strengths and limitations of this method.

Efficient Driving of Piezoelectric Transducers Using a Biaxial Driving Technique

PubMed Central

2015-01-01

Efficient driving of piezoelectric materials is desirable when operating transducers for biomedical applications such as high intensity focused ultrasound (HIFU) or ultrasound imaging. More efficient operation reduces the electric power required to produce the desired bioeffect or contrast. Our preliminary work [Cole et al. Journal of Physics: Condensed Matter. 2014;26(13):135901.] suggested that driving transducers by applying orthogonal electric fields can significantly reduce the coercivity that opposes ferroelectric switching. We present here the experimental validation of this biaxial driving technique using piezoelectric ceramics typically used in HIFU. A set of narrow-band transducers was fabricated with two sets of electrodes placed in an orthogonal configuration (following the propagation and the lateral mode). The geometry of the ceramic was chosen to have a resonance frequency similar for the propagation and the lateral mode. The average (± s.d.) resonance frequency of the samples was 465.1 (± 1.5) kHz. Experiments were conducted in which each pair of electrodes was driven independently and measurements of effective acoustic power were obtained using the radiation force method. The efficiency (acoustic/electric power) of the biaxial driving method was compared to the results obtained when driving the ceramic using electrodes placed only in the pole direction. Our results indicate that the biaxial method increases efficiency from 50% to 125% relative to the using a single electric field. PMID:26418550

H1 antihistamines and driving.

PubMed

Popescu, Florin Dan

2008-01-01

Driving performances depend on cognitive, psychomotor and perception functions. The CNS adverse effects of some H1 antihistamines can alter the patient ability to drive. Data from studies using standardized objective cognitive and psychomotor tests (Choice Reaction Time, Critical Flicker Fusion. Digital Symbol Substitution Test), functional brain imaging (Positron Emission Tomography, functional Magnetic Resonance Imaging), neurophysiological studies (Multiple Sleep Latency Test, auditory and visual evoked potentials), experimental simulated driving (driving simulators) and real driving studies (the Highway Driving Test, with the evaluation of the Standard Deviation Lateral Position, and the Car Following Test, with the measurement of the Brake Reaction Time) must be discussed in order to classify a H1 antihistamine as a true non-sedating one.

The Cohesive Population Genetics of Molecular Drive

PubMed Central

Ohta, Tomoko; Dover, Gabriel A.

1984-01-01

The long-term population genetics of multigene families is influenced by several biased and unbiased mechanisms of nonreciprocal exchanges (gene conversion, unequal exchanges, transposition) between member genes, often distributed on several chromosomes. These mechanisms cause fluctuations in the copy number of variant genes in an individual and lead to a gradual replacement of an original family of n genes (A) in N number of individuals by a variant gene (a). The process for spreading a variant gene through a family and through a population is called molecular drive. Consideration of the known slow rates of nonreciprocal exchanges predicts that the population variance in the copy number of gene a per individual is small at any given generation during molecular drive. Genotypes at a given generation are expected only to range over a small section of all possible genotypes from one extreme (n number of A) to the other (n number of a). A theory is developed for estimating the size of the population variance by using the concept of identity coefficients. In particular, the variance in the course of spreading of a single mutant gene of a multigene family was investigated in detail, and the theory of identity coefficients at the state of steady decay of genetic variability proved to be useful. Monte Carlo simulations and numerical analysis based on realistic rates of exchange in families of known size reveal the correctness of the theoretical prediction and also assess the effect of bias in turnover. The population dynamics of molecular drive in gradually increasing the mean copy number of a variant gene without the generation of a large variance (population cohesion) is of significance regarding potential interactions between natural selection and molecular drive. PMID:6500260

The cohesive population genetics of molecular drive.

PubMed

Ohta, T; Dover, G A

1984-10-01

The long-term population genetics of multigene families is influenced by several biased and unbiased mechanisms of nonreciprocal exchanges (gene conversion, unequal exchanges, transposition) between member genes, often distributed on several chromosomes. These mechanisms cause fluctuations in the copy number of variant genes in an individual and lead to a gradual replacement of an original family of n genes (A) in N number of individuals by a variant gene (a). The process for spreading a variant gene through a family and through a population is called molecular drive. Consideration of the known slow rates of nonreciprocal exchanges predicts that the population variance in the copy number of gene a per individual is small at any given generation during molecular drive. Genotypes at a given generation are expected only to range over a small section of all possible genotypes from one extreme (n number of A) to the other (n number of a). A theory is developed for estimating the size of the population variance by using the concept of identity coefficients. In particular, the variance in the course of spreading of a single mutant gene of a multigene family was investigated in detail, and the theory of identity coefficients at the state of steady decay of genetic variability proved to be useful. Monte Carlo simulations and numerical analysis based on realistic rates of exchange in families of known size reveal the correctness of the theoretical prediction and also assess the effect of bias in turnover. The population dynamics of molecular drive in gradually increasing the mean copy number of a variant gene without the generation of a large variance (population cohesion) is of significance regarding potential interactions between natural selection and molecular drive.

Driving Competence in Mild Dementia with Lewy Bodies: In Search of Cognitive Predictors Using Driving Simulation

PubMed Central

Yamin, Stephanie; Stinchcombe, Arne; Gagnon, Sylvain

2015-01-01

Driving is a multifactorial behaviour drawing on multiple cognitive, sensory, and physical systems. Dementia is a progressive and degenerative neurological condition that impacts the cognitive processes necessary for safe driving. While a number of studies have examined driving among individuals with Alzheimer's disease, less is known about the impact of Dementia with Lewy Bodies (DLB) on driving safety. The present study compared simulated driving performance of 15 older drivers with mild DLB with that of 21 neurologically healthy control drivers. DLB drivers showed poorer performance on all indicators of simulated driving including an increased number of collisions in the simulator and poorer composite indicators of overall driving performance. A measure of global cognitive function (i.e., the Mini Mental State Exam) was found to be related to the overall driving performance. In addition, measures of attention (i.e., Useful Field of View, UFOV) and space processing (Visual Object and Space Perception, VOSP, Test) correlated significantly with a rater's assessment of driving performance. PMID:26713169

Conserved interdomain linker promotes phase separation of the multivalent adaptor protein Nck

PubMed Central

Banjade, Sudeep; Wu, Qiong; Mittal, Anuradha; Peeples, William B.; Pappu, Rohit V.; Rosen, Michael K.

2015-01-01

The organization of membranes, the cytosol, and the nucleus of eukaryotic cells can be controlled through phase separation of lipids, proteins, and nucleic acids. Collective interactions of multivalent molecules mediated by modular binding domains can induce gelation and phase separation in several cytosolic and membrane-associated systems. The adaptor protein Nck has three SRC-homology 3 (SH3) domains that bind multiple proline-rich segments in the actin regulatory protein neuronal Wiskott-Aldrich syndrome protein (N-WASP) and an SH2 domain that binds to multiple phosphotyrosine sites in the adhesion protein nephrin, leading to phase separation. Here, we show that the 50-residue linker between the first two SH3 domains of Nck enhances phase separation of Nck/N-WASP/nephrin assemblies. Two linear motifs within this element, as well as its overall positively charged character, are important for this effect. The linker increases the driving force for self-assembly of Nck, likely through weak interactions with the second SH3 domain, and this effect appears to promote phase separation. The linker sequence is highly conserved, suggesting that the sequence determinants of the driving forces for phase separation may be generally important to Nck functions. Our studies demonstrate that linker regions between modular domains can contribute to the driving forces for self-assembly and phase separation of multivalent proteins. PMID:26553976