Academic literature on the topic 'Among-site rate variation'
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Journal articles on the topic "Among-site rate variation"
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Sullivan, Jack. "Combining Data with Different Distributions of Among-Site Rate Variation." Systematic Biology 45, no. 3 (September 1, 1996): 375–80. http://dx.doi.org/10.1093/sysbio/45.3.375.
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Yang, Ziheng. "Among-site rate variation and its impact on phylogenetic analyses." Trends in Ecology & Evolution 11, no. 9 (September 1996): 367–72. http://dx.doi.org/10.1016/0169-5347(96)10041-0.
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Sullivan, Jack, Kent E. Holsinger, and Chris Simon. "The effect of topology on estimates of among-site rate variation." Journal of Molecular Evolution 42, no. 2 (February 1996): 308–12. http://dx.doi.org/10.1007/bf02198857.
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Zhang, Jianzhi, and Xun Gu. "Correlation Between the Substitution Rate and Rate Variation Among Sites in Protein Evolution." Genetics 149, no. 3 (July 1, 1998): 1615–25. http://dx.doi.org/10.1093/genetics/149.3.1615.
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Abstract It is well known that the rate of amino acid substitution varies among different proteins and among different sites of a protein. It is, however, unclear whether the extent of rate variation among sites of a protein and the mean substitution rate of the protein are correlated. We used two approaches to analyze orthologous protein sequences of 51 nuclear genes of vertebrates and 13 mitochondrial genes of mammals. In the first approach, no assumptions of the distribution of the rate variation among sites were made, and in the second approach, the gamma distribution was assumed. Through both approaches, we found a negative correlation between the extent of among-site rate variation and the average substitution rate of a protein. That is, slowly evolving proteins tend to have a high level of rate variation among sites, and vice versa. We found this observation consistent with a simple model of the neutral theory where most sites are either invariable or neutral. We conclude that the correlation is a general feature of protein evolution and discuss its implications in statistical tests of positive Darwinian selection and molecular time estimation of deep divergences.
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Tajima, Fumio. "The Amount of DNA Polymorphism Maintained in a Finite Population When the Neutral Mutation Rate Varies Among Sites." Genetics 143, no. 3 (July 1, 1996): 1457–65. http://dx.doi.org/10.1093/genetics/143.3.1457.
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Abstract The expectations of the average number of nucleotide differences per site (π), the proportion of segregating site (s), the minimum number of mutations per site (s*) and some other quantities were derived under the finite site models with and without rate variation among sites, where the finite site models include Jukes and Cantor's model, the equal-input model and Kimura's model. As a model of rate variation, the gamma distribution was used. The results indicate that if distribution parameter α is small, the effect of rate variation on these quantities are substantial, so that the estimates of θ based on the infinite site model are substantially underestimated, where θ = 4Nv, N is the effective population size and vis the mutation rate per site per generation. New methods for estimating θ are also presented, which are based on the finite site models with and without rate variation. Using these methods, underestimation can be corrected.
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Van de Peer, Yves, and Rupert De Wachter. "Evolutionary Relationships Among the Eukaryotic Crown Taxa Taking into Account Site-to-Site Rate Variation in 18S rRNA." Journal of Molecular Evolution 45, no. 6 (December 1997): 619–30. http://dx.doi.org/10.1007/pl00006266.
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Reyes, Aurelio, Graziano Pesole, and Cecilia Saccone. "Long-branch attraction phenomenon and the impact of among-site rate variation on rodent phylogeny." Gene 259, no. 1-2 (December 2000): 177–87. http://dx.doi.org/10.1016/s0378-1119(00)00438-8.
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Sheffield, Nathan C. "The Interaction between Base Compositional Heterogeneity and Among-Site Rate Variation in Models of Molecular Evolution." ISRN Evolutionary Biology 2013 (December 26, 2013): 1–8. http://dx.doi.org/10.5402/2013/391561.
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Many commonly used models of molecular evolution assume homogeneous nucleotide frequencies. A deviation from this assumption has been shown to cause problems for phylogenetic inference. However, some claim that only extreme heterogeneity affects phylogenetic accuracy and suggest that violations of other model assumptions, such as variable rates among sites, are more problematic. In order to explore the interaction between compositional heterogeneity and variable rates among sites, I reanalyzed 3 real heterogeneous datasets using several models. My Bayesian inference recovers accurate topologies under variable rates-among-sites models, but fails under some models that account for compositional heterogeneity. I also ran simulations and found that accounting for rates among sites improves topology accuracy in compositionally heterogeneous data. This indicates that in some cases, models accounting for among-site rate variation can improve outcomes for data that violates the assumption of compositional homogeneity.
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Meyer, Austin G., Eric T. Dawson, and Claus O. Wilke. "Cross-species comparison of site-specific evolutionary-rate variation in influenza haemagglutinin." Philosophical Transactions of the Royal Society B: Biological Sciences 368, no. 1614 (March 19, 2013): 20120334. http://dx.doi.org/10.1098/rstb.2012.0334.
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We investigate the causes of site-specific evolutionary-rate variation in influenza haemagglutinin (HA) between human and avian influenza, for subtypes H1, H3, and H5. By calculating the evolutionary-rate ratio, ω = d N /d S as a function of a residue's solvent accessibility in the three-dimensional protein structure, we show that solvent accessibility has a significant but relatively modest effect on site-specific rate variation. By comparing rates within HA subtypes among host species, we derive an upper limit to the amount of variation that can be explained by structural constraints of any kind. Protein structure explains only 20–40% of the variation in ω . Finally, by comparing ω at sites near the sialic-acid-binding region to ω at other sites, we show that ω near the sialic-acid-binding region is significantly elevated in both human and avian influenza, with the exception of avian H5. We conclude that protein structure, HA subtype, and host biology all impose distinct selection pressures on sites in influenza HA.
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Waters, C., G. Melville, and A. Grice. "Genotypic variation among sites within eleven Australian native grasses." Rangeland Journal 25, no. 1 (2003): 70. http://dx.doi.org/10.1071/rj03006.
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Eleven species of native grass were collected from 51 sites throughout western New South Wales and south-west Queensland. Approximately 10 whole plants of each species were collected from a site but not all species were collected from each site. Plants were grown in a common environment at Trangie in central western New South Wales and plant morphological and floristic characteristics measured. Data reported here are for observations made in the third year, by which time differences between populations were likely to be more genetic than environmental. Principal component and discriminant analyses revealed a strong relationship between site of origin and plant morphological characteristics, which explained between 61% and 93% of the variation within species. For all but one species, site was significantly correlated with these morphological characteristics. Site could be predicted from morphological characters with a success rate usually greater than 80%. These morphological characteristics must reflect genotypic differences among the collection from the different sites. We were unable to relate this variation to any of a range of site characteristics. Distance between sites could not be used as an indicator of morphological differences between populations. The implications of these findings are discussed in terms of providing strong evidence for the existence of ecotypes and for obtaining appropriate seed sources for revegetation/restoration programs.
Dissertations / Theses on the topic "Among-site rate variation"
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Soubrier, Julien Benoit Adrien. "What (molecular) time is it? : using ancient DNA to date evolutionary events." Thesis, 2012. http://hdl.handle.net/2440/96464.
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This work aims to explore the use of genetic sequences sampled serially through time (heterochronous data), to infer the timescale of past evolutionary events. Such data can be generated from preserved sub-fossil or fossil organismal remains (like mummified tissues, fossilized bones or coprolites), and then used to observe genetic modifications in real-time. Most importantly, the dates of the samples provide firm temporal tie points for their genetic sequences, and can be used to calibrate phylogenetic reconstructions. This thesis presents several case studies where ancient DNA was used to re-calibrate evolutionary timescales. In every situation, the use of heterochronous data led to elevated molecular rate estimates, resulting in the reconstruction of younger timescales, as compared to estimates based on fossil calibrations. These observations are in agreement with the recent demonstration that molecular rates vary according to the time period over which they are calculated.
This work shows that, ancient DNA offers crucial temporal information to reliably estimate the timescale of recent population evolution, and is generally the only source of direct calibration available for this specific timeframe. Along with the results specific to each organism studied (hyena, bison and human), an emphasis was placed on the methodological aspects of the use of ancient DNA to generate timed phylogenetic inferences. Additionally, simulated data and mathematical modelling were used to extend the understanding of specific aspects of the temporal dependence of molecular rates. The results discussed in the present study help to further elucidate the evolutionary mechanisms behind the molecular clock concept, and have implications for the development and application of statistical models to obtain accurate time estimates from genetic data.Thesis (Ph.D.) -- University of Adelaide, School of Earth and Environmental Sciences, 2012
Book chapters on the topic "Among-site rate variation"
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Xia, Xuhua. "Phylogenetic Bias in the Likelihood Method Caused by Missing Data Coupled with Among-Site Rate Variation: An Analytical Approach." In Bioinformatics Research and Applications, 12–23. Cham: Springer International Publishing, 2014. http://dx.doi.org/10.1007/978-3-319-08171-7_2.
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Chowdhury, Rinku Roy, and Laura C. Schneider. "Land Cover and Land Use: Classification and Change Analysis." In Integrated Land-Change Science and Tropical Deforestation in the Southern Yucatan. Oxford University Press, 2004. http://dx.doi.org/10.1093/oso/9780199245307.003.0015.
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Despite its international designation as a hotspot of biodiversity and tropical deforestation (Achard et al. 1988), the micro-scale land-cover mapping of southern Yucatán peninsular region remains surprisingly incomplete, hindering various kinds of research, including that proposed in the SYPR project. This chapter details the methodology for the thematic classification and change detection of land use and cover in the tropical sub-humid environment of the region. A hybrid approach using principal components and texture analyses of Landsat TM data enabled the distinction of land-cover classes at the local scale, including mature and secondary forest, savannas, and cropland/pasture. Results indicate that texture analysis increases the statistical separability of cover class signatures, the magnitude of improvement varying among pairs of land-cover classes. At a local level, the availability of exhaustive training site data over recent history (10–13 years) in a repository of highly detailed land-use sketch maps allows the distinction of greater numbers of land-cover classes, including three successional stages of vegetation. At the regional scale, finely detailed land-cover classes are aggregated for greater ability to generalize in a terrain wherein vegetation exhibits marked regional and seasonal variation in intra-class spectral properties. Post-classification change detection identifies the quantities and spatial pattern of major land-cover changes in a ten-year period in the region. Change analysis results indicate an average annual rate of deforestation of 0.4 per cent, with much regional variation and most change located at three subregional hotspots. Deforestation as well as successional regrowth is highest in a southern hotspot located in the newly colonized southern part of the region, an area where commercial chili production is large. The objectives of this chapter are to describe and evaluate: (1) an experimental methodology that iteratively combines three suites of image-processing techniques (PCA, texture transformation, and NDVI); (2) the statistical separability of distinct land-cover signatures; and (3) a post-classification change detection for the region from 1987 to 1997 in order to derive regional deforestation rates, and identify the spatial pattern of deforestation and secondary forest succession. Specifically, a region encompassing 18,700km2 (those land units completely within the defined region; Fig. 7.1) was mapped using a maximum likelihood supervised classification of lower-order principal components of Landsat TM imagery after tasseled-cap and texture transformations.
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Hagino, Hiroshi, and Akiko Kondo. "Common fractures in older adults." In Oxford Textbook of Geriatric Medicine, 533–38. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780198701590.003.0069.
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Among elderly individuals worldwide, the incidence of fractures is highest in the vertebrae, followed by the hips and distal forearms. There is a wide variation in global hip fracture incidence rates, with the rates in women approximately twice those in men. These rates are low in people under 70 years old, and increase exponentially with age thereafter. There are large geographic and secular changes in incidence of most common fragility fractures, for reasons that are not fully understood. Morbidity and mortality increases are associated with all fragility fractures, although to varying degrees depending on the site of the fracture. The mean decline in quality of life is greater in patients with hip fractures, than those with vertebral or distal forearm fractures.
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Belu, Radian. "Assessment and Analysis of Offshore Wind Energy Potential." In Wind Farms - Increasing Penetration, Economic Dispatch and Operational Planning [Working Title]. IntechOpen, 2020. http://dx.doi.org/10.5772/intechopen.95346.
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Wind energy usage is increasing at fast rates due to significant technical advances, energy supply security and environmental concerns. Research is focusing among others areas on the development of reliable and accurate wind energy assessment methods. Offshore wind energy resources are usually larger than at geographically nearby onshore sites, which may offset in part higher installation, operation, and maintenance costs. Successful offshore wind energy development relies on accurate analysis and assessment of wind energy resource potential. Offshore wind assessment challenges are related to the wind turbine size, offshore installation challenges, lack of adequate and long-term wind and meteorological measurements, etc. Wind, a highly intermittent phenomenon has large spatiotemporal variability, being subject to sub-hourly, hourly, diurnal, seasonal, yearly, and climate variations in addition to their dependence on the geography and environment. Wind regime characteristics are critical to all aspect of a wind energy project, e.g. potential site identification, economic viability, equipment design, operation, management, or wind farm impacts on the electric grid. For a reliable wind energy assessment, measurements at rotor heights are required at least for one year. If such measurements are not available needs to be substituted by alternative approaches, e.g. measure-correlate-predict or numerical methods. Chapter objectives are to provide the reader with comprehensive reviews of the wind energy assessment and analysis methods.
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Goodin, Douglas G., and Raymond C. Smith. "Century to Millennial Timescale—Synthesis." In Climate Variability and Ecosystem Response in Long-Term Ecological Research Sites. Oxford University Press, 2003. http://dx.doi.org/10.1093/oso/9780195150599.003.0034.
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At longer timescales, the interaction among climate, ecosystems, and the abiotic components of the environment become increasingly important. These relationships are apparent in the three chapters in part IV. Fountain and Lyons (chapter 16), examining the McMurdo Dry Valleys (MCM) ecosystem in Antarctic, provide an excellent example of a case where past climatic variations truly dictate current ecosystem status. The relatively large climate variations at MCM have concentrated nutrients that could not have been attained without this climate variability. Fountain and Lyons infer climate change from geomorphic evidence of past glacier positions and lake level heights as well as more recent isotopic results from ice cores and temperature measurements from boreholes. They focus on evidence from the most recent 60,000 years. Monger (chapter 17) provides an analysis of millennial-scale climate and ecosystem variability at the Jornada LTER site in southern New Mexico. Monger notes the difficulty of untangling prehistoric climate/ecosystem interactions, where researchers must rely on indirect proxy indicators in lieu of measured data. Monger analyzes a number of proxy data sources, including paleolake levels, plant remnants preserved in packrat middens, fossil pollens, carbon isotope ratios in paleosols, and erosion rates. Although noting the danger of circular reasoning in using proxy data (i.e., ecosystem response used to infer information about climatic change, which is in turn inferred from ecosystem response) Monger uses these data to construct a cogent picture of climate change at the Jornada site (JRN) since the Last Glacial Maximum (LGM) about 18,000–20,000 years b.p. Using remains of beetles, Elias (chapter 18) constructs a temperature history of the Colorado Alpine since the LGM. These late Holocene insect records show a progression from warmer-than-modern to coolerthan- modern summers, and back to warm again. All the authors in this section provide examples to show that it is at century to millennial timescales that ecosystems form, are broken apart and imprinted by the past, and reformed in new configurations. The McMurdo Dry Valleys is the most poleward-terrestrial ecosystem where streams, lakes, and soil are interconnected. In this polar desert, the biotic system must adopt a strategy to survive the winter in isolation, and the disturbance and formation of the landscape has been primarily dictated by climate and associated abiotic processes. During the last glacial period, the Ross Ice shelf entered Taylor Valley, damming the valley and forming a 200-m-deep lake (23.8 kyrs).
Conference papers on the topic "Among-site rate variation"
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Vafaee, Fatemeh, Gyorgy Turan, Peter C. Nelson, and Tanya Y. Berger-Wolf. "Among-site rate variation." In GECCO '14: Genetic and Evolutionary Computation Conference. New York, NY, USA: ACM, 2014. http://dx.doi.org/10.1145/2576768.2598216.
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Wang, Jun, Jiawu Li, Guang Hong, and Feng Wang. "Research on wind field characteristics measured in U-shaped valley at bridge site by Lidar." In IABSE Congress, Nanjing 2022: Bridges and Structures: Connection, Integration and Harmonisation. Zurich, Switzerland: International Association for Bridge and Structural Engineering (IABSE), 2022. http://dx.doi.org/10.2749/nanjing.2022.0733.
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<p>Currently, research on wind fields of U-shaped valleys is rarely reported. In order to study the wind characteristics in a mountainous U-shaped valley, a lidar was placed at a bridge site located in a U-shaped valley. Then, nearly 6 months of original data ranging from 0 m to 810 m were analyzed statistically. It was found that the wind parameters are correlated among different virtual wind towers (VWTs). The wind speed profile is divided into three categories: disordered, linear and nonlinear. The wind direction is consistent with the main wind direction at the bridge site and the average wind direction of different VWTs has a high consistency. The concept of wind-direction deflection rate is put forward to describe the variation of wind direction with height. These measured wind parameters could be used as a reference for bridge wind- resistant design.</p>
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Gupta, Vijay K., and Charles D. Eggleton. "A 3-D Computational Model of L-Selectin-PSGL-1 Dependent Homotypic Leukocyte Binding and Rupture in Shear Flow." In ASME 2012 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/sbc2012-80862.
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Cell adhesion plays a pivotal role in diverse biological processes, including inflammation, tumor metastasis, arteriosclerosis, and thrombosis. Changes in cell adhesion can be the defining event in a wide range of diseases, including cancer, atherosclerosis, osteoporosis, and arthritis. Cells are exposed constantly to hemodynamic/hydrodynamic forces and the balance between the dispersive hydrodynamic forces and the adhesive forces generated by the interactions of membrane-bound receptors and their ligands determines cell adhesion. Therefore to develop novel tissue engineering based approaches for therapeutic interventions in thrombotic disorders, inflammatory, and a wide range of other diseases, it is crucial to understand the complex interplay among blood flow, cell adhesion, and vascular biology at the molecular level. In response to tissue injury or infection, polymorphonuclear (PMN) leukocytes are recruited from the bloodstream to the site of inflammation through interactions between cell surface receptors and complementary ligands expressed on the surface of the endothelium [1]. PMN-PMN interactions also contribute to the process of recruitment. It has been shown that PMNs rolling on activated endothelium cells can mediate secondary capture of PMNs flowing in the free blood stream through homotypic interactions [2]. This is mediated by L-selectin (ligand) binding to PSGL-1 (receptor) between a free-stream PMN and one already adherent to the endothelium cells [3]. Both PSGL-1 and L-selectin adhesion molecules are concentrated on tips of PMN microvilli [4]. Homotypic PMN aggregation in vivo or in vitro is supported by multiple L-selectin–PSGL-1 bondings between pairs of microvilli. The ultimate objective of our work is to develop software that can simulate the adhesion of cells colliding under hydrodynamic forces that can be used to investigate the complex interplay among the physical mechanisms and scales involved in the adhesion process. However, cell-cell adhesion is a complex phenomenon involving the interplay of bond kinetics and hydrodynamics. Hence, as a first step we recently developed a 3-D computational model based on the Immersed Boundary Method to simulate adhesion-detachment of two PMN cells in quiescent conditions and the exposing the cells to external pulling forces and shear flow in order to investigate the behavior of the nano-scale molecular bonds to forces applied at the cellular scale [5]. Our simulations predicted that the total number of bonds formed is dependent on the number of available receptors (PSGL-1) when ligands (L-selectin) are in excess, while the excess amount of ligands controls the rate of bond formation [5]. Increasing equilibrium bond length causes an increased intercellular contact area hence results in a higher number of receptor-ligand bonds [5]. Off-rates control the average number of bonds by modulating bond lifetimes while On-rate constants determine the rate of bond formation [5]. An applied external pulling force leads to time-dependent on- and off-rates and causes bond rupture [5]. It was shown that the time required for bond rupture in response to an applied external force is inversely proportional to the applied external force and decreases with increasing offrate [5]. Fig. 1 shows the time evolution of the total number of bonds formed for various values of NRmv (number of receptor) and NLmv (number of ligand). As expected, the total number of bonds formed at equilibrium is dependent on NRmv when NLmv is in excess. In this particular case study since two pairs (or four) microvilli each with NRmv are involved in adhesion hence the equilibrium bond number is approximately 4NRmv. It is noticed that for NRmv = 50, as we vary NLmv the mean value of the total number of bonds at equilibrium does not change appreciably. However, it can be noticed from Fig. 1 that for NRmv = 50, as the excess number of ligands (NLmv) increases there is a slight increase in the rate of bond formation due to the increase in probability of bond formation. Having developed confidence in the ability of the numerical method to simulate the adhesion of two cells that can form up to 200 bonds, we apply the method to study the effect of shear rate on the detachment of two cells. In particular, we first would like to establish the minimum shear rate needed for the two cells to detach for a given number of bonds between them. Fig. 2 shows the variation of force per bond at no rupture with number of bonds for various shear rates indicated. It is seen that at a given shear rate as the number of bonds increases the force per bond at no rupture decreases. This is attributed to the fact that force caused by shear flow is shared equally among the existing bonds. Further, it is seen that a given number of bonds as the shear rate increases the force per bond at no rupture increases. This is due to the fact that at a given number of bonds between the cells as we increase the shear rate the force caused by the flow increases hence the force per bond increases. We further notice that at shear rate = 3000 s−1 cells attached either by a single bond or by two bonds detach while they don’t for higher (> 2) number of bonds. This clearly demonstrate that there is a minimum shear rate needed to detach cells adhered by a given number of bonds. The higher the number of bonds, the higher the minimum shear rate for complete detachment of cells. For example, from Fig. 2 is it clear that for the cells adhered by two and five bonds the minimum shear rate needed for complete detachment of these two cells are 3000 s−1 and 6000 s−1, respectively.
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Fitriyani, L. "Biosurfactant Addition into Solvent Extraction Process of Oily Contaminated Solid Waste." In Digital Technical Conference. Indonesian Petroleum Association, 2020. http://dx.doi.org/10.29118/ipa20-o-435.
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Solvent extraction has been used in industry or many purposes for years, including to recover oil at contaminated soil. Certain solvents and temperature ranges have been chosen to increase the oil recovery rate of extraction process. The Study observed the implementation of biosurfactant at the extraction process to perform reduction of total petroleum hydrocarbon (TPH) concentration of oily contaminated soil. In order to optimize TPH removal, extraction were conducted for multiple stages. Biosurfactant extraction result were also compared to solvent extraction process which acetone and toluene have been selected to extract oil content from contaminated soil by using solvent extraction process. The combination treatments with biosurfactant were also involving variety of centrifugation process with 1000 rpm (1570 g) operational speed. Duration of treatment process was 10 minutes with some variations of solid to solvent ratio. During the experiments comparison result between varies treatment process provides alternatives to treat oily contaminated soil by using extraction process. Compatibility among solvents, biosurfactants, types of oily contaminated solid waste were also observed to seek possibility on large scale of treatment process implementation both insitu at the contaminated site and exsitu at integrated waste treatment facility.
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Robinson, Franklin L., and Avram Bar-Cohen. "Orientation Effects in Two-Phase Microgap Flow." In ASME 2018 International Technical Conference and Exhibition on Packaging and Integration of Electronic and Photonic Microsystems. American Society of Mechanical Engineers, 2018. http://dx.doi.org/10.1115/ipack2018-8383.
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The high power density of emerging electronic devices is driving the transition from remote cooling, which relies on conduction and spreading, to embedded cooling, which extracts dissipated heat on-site. Two-phase microgap coolers employ the forced flow of dielectric fluids undergoing phase change in a heated channel within or between devices. Such coolers must work reliably in all orientations for a variety of applications (e.g., vehicle-based equipment), as well as in microgravity and high-g for other applications (e.g., spacecraft and aircraft). The lack of acceptable models and correlations for orientation- and gravity-independent operation has limited the use of two-phase coolers in such applications. Previous research has revealed that gravitational acceleration plays a diminishing role in establishing flow regimes and transport rates as the channel size shrinks, but there is considerable variation among the proposed microscale criteria and limited research on two-phase flows in low aspect ratio microgap channels. Reliable criteria for achieving orientation- and gravity-independent flow boiling would enable emerging systems to exploit this thermal management technique and streamline the technology development process. As a first step toward understanding the effect of gravity on two-phase microgap flow and transport, in the present effort the authors have studied the effect of evaporator orientation and mass flux on near-saturated flow boiling of HFE7100 in a 1.01 mm tall by 13.0 mm wide by 12.7 mm long microgap channel. Orientation-independence, defined as achieving similar critical heat fluxes, heat transfer coefficients, and flow regimes across evaporator orientations, was achieved for mass fluxes of 400 kg/m2-s and greater. The present results are compared to published criteria for achieving gravity-independence.
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Gernand, Jeremy M. "Mitigating Crew Health Degradation During Long-Term Exposure to Microgravity Through Countermeasure System Implementation." In ASME 2004 International Mechanical Engineering Congress and Exposition. ASMEDC, 2004. http://dx.doi.org/10.1115/imece2004-59029.
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Experience with the International Space Station (ISS) program demonstrates the degree to which engineering design and operational solutions must protect crewmembers from health risks due to long-term exposure to the microgravity environment. Risks to safety and health due to degradation in the microgravity environment include crew inability to complete emergency or nominal activities, increased risk of injury, and inability to complete safe return to the ground due to reduced strength or embrittled bones. These risks without controls slowly increase in probability for the length of the mission and become more significant for increasing mission durations. Countermeasures to microgravity include hardware systems that place a crewmember’s body under elevated stress to produce an effect similar to daily exposure to gravity. The ISS countermeasure system is predominately composed of customized exercise machines. Historical treatment of microgravity countermeasure systems as medical research experiments unintentionally reduced the foreseen importance and therefore the capability of the systems to function in a long-term operational role. Long-term hazardous effects and steadily increasing operational risks due to non-functional countermeasure equipment require a more rigorous design approach and incorporation of redundancy into seemingly nonmission-critical hardware systems. Variations in the rate of health degradation and responsiveness to countermeasures among the crew population drastically increase the challenge for design requirements development and verification of the appropriate risk control strategy. The long-term nature of the hazards and severe limits on logistical re-supply mass, volume and frequency complicates assessment of hardware availability and verification of an adequate maintenance and sparing plan. Design achievement of medically defined performance requirements by microgravity countermeasure systems and incorporation of adequate failure tolerance significantly reduces these risks. Future implementation of on-site monitoring hardware for critical health parameters such as bone mineral density would allow greater responsiveness, efficiency, and optimized design of the countermeasures system.
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Pannekoek, H., M. Linders, J. Keijer, H. Veerman, H. Van Heerikhuizen, and D. J. Loskutoff. "THE STRUCTURE OF THE HUMAN ENDOTHELIAL PLASMINOGEN ACTIVATOR INHIBITOR (PAI-1) GENE: NON-RANDOM POSITIONING OF INTRONS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644767.
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The endothelium plays a crucial role in the regulation of the fibrinolytic process, since it synthesizes and secretes tissue-type plasminogen activator (t-PA) as well as the fast-acting plasminogen activator inhibitor (PAI-1). Molecular cloning of full-length PAI-1 cDNA, employing a human endothelial cDNA expression library, and a subsequent determination of the complete nucleotide sequence, allowed a prediction of the amino-acid sequence of the PAI-1 glycoprotein. It was observed that the amino-acid sequence is significantly homologous to those of members of the serine protease inhibitor ("Serpin") family, e.g. αl-antitrypsin and antithrombin III. Serpins are regulators of various processes, such as coagulation, inflammatory reactions, complement activation and share a common functional principle and a similar structure, indicative for a common primordial gene. The intron-exon arrangement of Serpin genes may provide a record for the structure of a primordial gene. A comparison of the location of introns among members of the Serpin family reveals that some introns are indeed present at identical or almost identical positions, however in many other cases there is no correspondence between the intron positions among different Serpin genes.Obviously, more data on the chromosomal gene structure of members of this family are required to formulate a scheme for the evolutionary creation of the Serpins. To that end, we have established the number and the precise location of the introns in the PAI-1 gene and have compared these data with those reported on other Serpin genes. For that purpose a human genomic cosmid DNA library of about 340.000 independent colonies was screened with radiolabelled full-length PAI-1 cDNA as probe. Two clones were found which contain the entire PAI-1 gene. Restriction site mapping, electron microscopic inspection of heteroduplexes and nucleotide sequence analysis demonstrate that the PAI-1 gene comprises about 12.2kilo basepairs and consists of nine exons and eight introns. Intron-exon boundaries are all in accord with the "GT-AG" rule, including a cryptic acceptor splice site found in intron 7. Furthermore, it is observed that intron 3 of the PAI-1 gene occupies an identical position as intron E of chicken ovalbumin and intron E of the ovalbumin-related gene Y. The location of the other seven introns is unrelated to the known location of introns in the genes encoding the Serpins, rat angiotensin, chicken ovalbumin (and gene Y), human antithrombin III and human al-antitrypsin. The 3' untranslated region of the PAI-1 gene is devoid of introns, indicating that the two mRNA species detected in cultured endothelial cells which share an identical 5' untranslated segment and codogenic region, but differ in the length of the 3' untranslated region, arise by alternative polyadenylation. An extrapolation of the position of the introns to the amino-acid sequence of PAI-1, and adaption of the view that the subdomain structure of the Serpins is analogous, shows that the introns of PAI-1 are non-randomly distributed. Except for intron 7, the position of the other seven introns corresponds with randon-coil regions of the protein or with the borders of β-sheets and a-helices. Extrapolation of the position of introns in the genes of other Serpins to their respective amino-acid sequences and subdomain structures also reveals a preference for random-coil regions and borders of subdomains. These observations are reminiscent of an evolutionary model, called "intron sliding", that accounts for variations in surface loops of the same protein in different species by aberrant splicing (Craik et al., Science 220 (1983) 1125). The preferential presence of introns in gene segments, encoding these variable regions, and absence in regions determining the general folding of these proteins would explain conservation of the structure during the evolution of those genes.