Computational study of stability of an H-H-type pseudoknot motif.

PubMed

Wang, Jun; Zhao, Yunjie; Wang, Jian; Xiao, Yi

2015-12-01

Motifs in RNA tertiary structures are important to their structural organizations and biological functions. Here we consider an H-H-type pseudoknot (HHpk) motif that consists of two hairpins connected by a junction loop and with kissing interactions between the two hairpin loops. Such a tertiary structural motif is recurrently found in RNA tertiary structures, but is difficult to predict computationally. So it is important to understand the mechanism of its formation and stability. Here we investigate the stability of the HHpk tertiary structure by using an all-atom molecular dynamics simulation. The results indicate that the HHpk tertiary structure is stable. However, it is found that this stability is not due to the helix-helix packing, as is usually expected, but is maintained by the combined action of the kissing hairpin loops and junctions, although the former plays the main role. Stable HHpk motifs may form structural platforms for the molecules to realize their biological functions. These results are useful for understanding the construction principle of RNA tertiary structures and structure prediction.

An Amino Acid Code for β-sheet Packing Structure

PubMed Central

Joo, Hyun; Tsai, Jerry

2014-01-01

To understand the relationship between protein sequence and structure, this work extends the knob-socket model in an investigation of β-sheet packing. Over a comprehensive set of β-sheet folds, the contacts between residues were used to identify packing cliques: sets of residues that all contact each other. These packing cliques were then classified based on size and contact order. From this analysis, the 2 types of 4 residue packing cliques necessary to describe β-sheet packing were characterized. Both occur between 2 adjacent hydrogen bonded β-strands. First, defining the secondary structure packing within β-sheets, the combined socket or XY:HG pocket consists of 4 residues i,i+2 on one strand and j,j+2 on the other. Second, characterizing the tertiary packing between β-sheets, the knob-socket XY:H+B consists of a 3 residue XY:H socket (i,i+2 on one strand and j on the other) packed against a knob B residue (residue k distant in sequence). Depending on the packing depth of the knob B residue, 2 types of knob-sockets are found: side-chain and main-chain sockets. The amino acid composition of the pockets and knob-sockets reveal the sequence specificity of β-sheet packing. For β-sheet formation, the XY:HG pocket clearly shows sequence specificity of amino acids. For tertiary packing, the XY:H+B side-chain and main-chain sockets exhibit distinct amino acid preferences at each position. These relationships define an amino acid code for β-sheet structure and provide an intuitive topological mapping of β-sheet packing. PMID:24668690

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

Ross, Howard P.; Moore, Joseph N.; Christensen, Odin D.

Geological, geochemical and geophysical data are presented for one of the major geothermal systems in the western United States. Regional data indicate major tectonic structures which are still active and provide the conduits for the geothermal system. Detailed geologic mapping has defined major glide blocks of Tertiary volcanics which moved down from the Tushar Mountains and locally act as a leaky cap to portions of the presently known geothermal system. Mapping and geochemical studies indicate three periods of mineralization have affected the area, two of which are unrelated to the present geothermal activity. The geologic relationships demonstrate that the majormore » structures have been opened repeatedly since the Tertiary. Gravity and magnetic data are useful in defining major structures beneath alluvium and basalt cover, and indicate the importance of the Cove Fort-Beaver graben and the Cove Creek fault in localizing the geothermal reservoir. These structures and a high level of microearthquake activity also suggest other target areas within the larger thermal anomaly. Electrical resistivity surveys and thermal gradient holes both contribute to the delineation of the known reservoir. Deep exploration wells which test the reservoir recorded maximum temperatures of 178 C and almost isothermal behavior beginning at 700 to 1000 m and continuing to a depth of 1800 m. Costly drilling, high corrosion rates and low reservoir pressure coupled with the relatively low reservoir temperatures have led to the conclusion that the reservoir is not economic for electric power production at present. Plans are underway to utilize the moderate-temperature fluids for agribusiness, and exploration continues for a deep high-temperature reservoir.« less

Analysis of Management Practices in Lagos State Tertiary Institutions through Total Quality Management Structural Framework

ERIC Educational Resources Information Center

AbdulAzeez, Abbas Tunde

2016-01-01

This research investigated total quality management practices and quality teacher education in public tertiary institutions in Lagos State. The study was therefore designed to analyse management practices in Lagos state tertiary institutions through total quality management structural framework. The selected public tertiary institutions in Lagos…

Dynamic covalent chemistry enables formation of antimicrobial peptide quaternary assemblies in a completely abiotic manner

NASA Astrophysics Data System (ADS)

Reuther, James F.; Dees, Justine L.; Kolesnichenko, Igor V.; Hernandez, Erik T.; Ukraintsev, Dmitri V.; Guduru, Rusheel; Whiteley, Marvin; Anslyn, Eric V.

2018-01-01

Naturally occurring peptides and proteins often use dynamic disulfide bonds to impart defined tertiary/quaternary structures for the formation of binding pockets with uniform size and function. Although peptide synthesis and modification are well established, controlling quaternary structure formation remains a significant challenge. Here, we report the facile incorporation of aryl aldehyde and acyl hydrazide functionalities into peptide oligomers via solid-phase copper-catalysed azide-alkyne cycloaddition (SP-CuAAC) click reactions. When mixed, these complementary functional groups rapidly react in aqueous media at neutral pH to form peptide-peptide intermolecular macrocycles with highly tunable ring sizes. Moreover, sequence-specific figure-of-eight, dumbbell-shaped, zipper-like and multi-loop quaternary structures were formed selectively. Controlling the proportions of reacting peptides with mismatched numbers of complementary reactive groups results in the formation of higher-molecular-weight sequence-defined ladder polymers. This also amplified antimicrobial effectiveness in select cases. This strategy represents a general approach to the creation of complex abiotic peptide quaternary structures.

Regional Tectonic Control of Tertiary Mineralization and Recent Faulting in the Southern Basin-Range Province, an Application of ERTS-1 Data

NASA Technical Reports Server (NTRS)

Bechtold, I. C.; Liggett, M. A.; Childs, J. F.

1973-01-01

Research based on ERTS-1 MSS imagery and field work in the southern Basin-Range Province of California, Nevada and Arizona has shown regional tectonic control of volcanism, plutonism, mineralization and faulting. This paper covers an area centered on the Colorado River between 34 15' N and 36 45' N. During the mid-Tertiary, the area was the site of plutonism and genetically related volcanism fed by fissure systems now exposed as dike swarms. Dikes, elongate plutons, and coeval normal faults trend generally northward and are believed to have resulted from east-west crustal extension. In the extensional province, gold silver mineralization is closely related to Tertiary igneous activity. Similarities in ore, structural setting, and rock types define a metallogenic district of high potential for exploration. The ERTS imagery also provides a basis for regional inventory of small faults which cut alluvium. This capability for efficient regional surveys of Recent faulting should be considered in land use planning, geologic hazards study, civil engineering and hydrology.

Acyl carrier protein structural classification and normal mode analysis

PubMed Central

Cantu, David C; Forrester, Michael J; Charov, Katherine; Reilly, Peter J

2012-01-01

All acyl carrier protein primary and tertiary structures were gathered into the ThYme database. They are classified into 16 families by amino acid sequence similarity, with members of the different families having sequences with statistically highly significant differences. These classifications are supported by tertiary structure superposition analysis. Tertiary structures from a number of families are very similar, suggesting that these families may come from a single distant ancestor. Normal vibrational mode analysis was conducted on experimentally determined freestanding structures, showing greater fluctuations at chain termini and loops than in most helices. Their modes overlap more so within families than between different families. The tertiary structures of three acyl carrier protein families that lacked any known structures were predicted as well. PMID:22374859

Magnetotelluric Data, Central Yucca Flat, Nevada Test Site, Nevada

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

J.M. Williams; B.D. Rodriguez, and T.H. Asch

2005-11-23

Nuclear weapons are integral to the defense of the United States. The U.S. Department of Energy, as the steward of these devices, must continue to gauge the efficacy of the individual weapons. This could be accomplished by occasional testing at the Nevada Test Site (NTS) in Nevada, northwest of Las Vegas. Yucca Flat Basin is one of the testing areas at the NTS. One issue of concern is the nature of the somewhat poorly constrained pre-Tertiary geology and its effects on ground-water flow in the area subsequent to a nuclear test. Ground-water modelers would like to know more about themore » hydrostratigraphy and geologic structure to support a hydrostratigraphic framework model that is under development for the Yucca Flat Corrective Action Unit (CAU). During 2003, the U.S. Geological Survey (USGS) collected and processed Magnetotelluric (MT) and Audio-magnetotelluric (AMT) data at the Nevada Test Site in and near Yucca Flat to help characterize this pre-Tertiary geology. That work will help to define the character, thickness, and lateral extent of pre-Tertiary confining units. In particular, a major goal has been to define the upper clastic confining unit (UCCU) in the Yucca Flat area. Interpretation will include a three-dimensional (3-D) character analysis and two-dimensional (2-D) resistivity model. The purpose of this report is to release the MT sounding data for Central Yucca Flat, Profile 1, as shown in figure 1. No interpretation of the data is included here.« less

Magnetotelluric Data, North Central Yucca Flat, Nevada Test Site, Nevada

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

J.M. Williams; B.D. Rodriguez, and T.H. Asch

2005-11-23

Nuclear weapons are integral to the defense of the United States. The U.S. Department of Energy, as the steward of these devices, must continue to gauge the efficacy of the individual weapons. This could be accomplished by occasional testing at the Nevada Test Site (NTS) in Nevada, northwest of Las Vegas. Yucca Flat Basin is one of the testing areas at the NTS. One issue of concern is the nature of the somewhat poorly constrained pre-Tertiary geology and its effects on ground-water flow in the area subsequent to a nuclear test. Ground-water modelers would like to know more about themore » hydrostratigraphy and geologic structure to support a hydrostratigraphic framework model that is under development for the Yucca Flat Corrective Action Unit (CAU). During 2003, the U.S. Geological Survey (USGS) collected and processed Magnetotelluric (MT) and Audio-magnetotelluric (AMT) data at the Nevada Test Site in and near Yucca Flat to help characterize this pre-Tertiary geology. That work will help to define the character, thickness, and lateral extent of pre-Tertiary confining units. In particular, a major goal has been to define the upper clastic confining unit (UCCU) in the Yucca Flat area. Interpretation will include a three-dimensional (3-D) character analysis and two-dimensional (2-D) resistivity model. The purpose of this report is to release the MT sounding data for north central Yucca Flat, Profile 7, as shown in Figure 1. No interpretation of the data is included here.« less

Magnetotelluric Data, Northern Frenchman Flat, Nevada Test Site Nevada

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

J.M. Williams; B.D. Rodriguez, and T. H. Asch

2005-11-23

Nuclear weapons are integral to the defense of the United States. The U.S. Department of Energy, as the steward of these devices, must continue to gauge the efficacy of the individual weapons. This could be accomplished by occasional testing at the Nevada Test Site (NTS) in Nevada, northwest of Las Vegas. Yucca Flat Basin is one of the testing areas at the NTS. One issue of concern is the nature of the somewhat poorly constrained pre-Tertiary geology and its effects on ground-water flow in the area subsequent to a nuclear test. Ground-water modelers would like to know more about themore » hydrostratigraphy and geologic structure to support a hydrostratigraphic framework model that is under development for the Yucca Flat Corrective Action Unit (CAU). During 2003, the U.S. Geological Survey (USGS) collected and processed Magnetotelluric (MT) and Audio-magnetotelluric (AMT) data at the Nevada Test Site in and near Yucca Flat to help characterize this pre-Tertiary geology. That work will help to define the character, thickness, and lateral extent of pre-Tertiary confining units. In particular, a major goal has been to define the upper clastic confining unit (UCCU) in the Yucca Flat area. Interpretation will include a three-dimensional (3-D) character analysis and two-dimensional (2-D) resistivity model. The purpose of this report is to release the MT sounding data for Frenchman Flat Profile 3, as shown in Figure 1. No interpretation of the data is included here.« less

Magnetotelluric Data, Across Quartzite Ridge, Nevada Test Site, Nevada

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

J.M. Williams; B.D. Rodriguez, and T.H. Asch

2005-11-23

Nuclear weapons are integral to the defense of the United States. The U.S. Department of Energy, as the steward of these devices, must continue to gauge the efficacy of the individual weapons. This could be accomplished by occasional testing at the Nevada Test Site (NTS) in Nevada, northwest of Las Vegas. Yucca Flat Basin is one of the testing areas at the NTS. One issue of concern is the nature of the somewhat poorly constrained pre-Tertiary geology and its effects on ground-water flow in the area subsequent to a nuclear test. Ground-water modelers would like to know more about themore » hydrostratigraphy and geologic structure to support a hydrostratigraphic framework model that is under development for the Yucca Flat Corrective Action Unit (CAU). During 2003, the U.S. Geological Survey (USGS) collected and processed Magnetotelluric (MT) and Audio-magnetotelluric (AMT) data at the Nevada Test Site in and near Yucca Flat to help characterize this pre-Tertiary geology. That work will help to define the character, thickness, and lateral extent of pre-Tertiary confining units. In particular, a major goal has been to define the upper clastic confining unit (UCCU) in the Yucca Flat area. Interpretation will include a three-dimensional (3-D) character analysis and two-dimensional (2-D) resistivity model. The purpose of this report is to release the MT soundings across Quartzite Ridge, Profiles 5, 6a, and 6b, as shown in Figure 1. No interpretation of the data is included here.« less

Magnetotelluric Data, Southern Yucca Flat, Nevada Test Site, Nevada

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

J.M. Williams; B.D. Rodriguez, and T.H. Asch

2005-11-23

Nuclear weapons are integral to the defense of the United States. The U.S. Department of Energy, as the steward of these devices, must continue to gauge the efficacy of the individual weapons. This could be accomplished by occasional testing at the Nevada Test Site (NTS) in Nevada, northwest of Las Vegas. Yucca Flat Basin is one of the testing areas at the NTS. One issue of concern is the nature of the somewhat poorly constrained pre-Tertiary geology and its effects on ground-water flow in the area subsequent to a nuclear test. Ground-water modelers would like to know more about themore » hydrostratigraphy and geologic structure to support a hydrostratigraphic framework model that is under development for the Yucca Flat Corrective Action Unit (CAU). During 2003, the U.S. Geological Survey (USGS) collected and processed Magnetotelluric (MT) and Audio-magnetotelluric (AMT) data at the Nevada Test Site in and near Yucca Flat to help characterize this pre-Tertiary geology. That work will help to define the character, thickness, and lateral extent of pre-Tertiary confining units. In particular, a major goal has been to define the upper clastic confining unit (UCCU) in the Yucca Flat area. Interpretation will include a three-dimensional (3-D) character analysis and two-dimensional (2-D) resistivity model. The purpose of this report is to release the MT sounding data for Southern Yucca Flat, Profile 4, as shown in Figure 1. No interpretation of the data is included here.« less

Magnetotelluric Data, Northern Yucca Flat, Nevada Test Site, Nevada

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

J.M. Williams; B.D. Rodriguez, and T.H. Asch

2005-11-23

Nuclear weapons are integral to the defense of the United States. The U.S. Department of Energy, as the steward of these devices, must continue to gauge the efficacy of the individual weapons. This could be accomplished by occasional testing at the Nevada Test Site (NTS) in Nevada, northwest of Las Vegas. Yucca Flat Basin is one of the testing areas at the NTS. One issue of concern is the nature of the somewhat poorly constrained pre-Tertiary geology and its effects on ground-water flow in the area subsequent to a nuclear test. Ground-water modelers would like to know more about themore » hydrostratigraphy and geologic structure to support a hydrostratigraphic framework model that is under development for the Yucca Flat Corrective Action Unit (CAU). During 2003, the U.S. Geological Survey (USGS) collected and processed Magnetotelluric (MT) and Audio-magnetotelluric (AMT) data at the Nevada Test Site in and near Yucca Flat to help characterize this pre-Tertiary geology. That work will help to define the character, thickness, and lateral extent of pre-Tertiary confining units. In particular, a major goal has been to define the upper clastic confining unit (UCCU) in the Yucca Flat area. Interpretation will include a three-dimensional (3-D) character analysis and two-dimensional (2-D) resistivity model. The purpose of this report is to release the MT sounding data for Profile 2, (fig. 1), located in the northern Yucca Flat area. No interpretation of the data is included here.« less

Automated and fast building of three-dimensional RNA structures.

PubMed

Zhao, Yunjie; Huang, Yangyu; Gong, Zhou; Wang, Yanjie; Man, Jianfen; Xiao, Yi

2012-01-01

Building tertiary structures of non-coding RNA is required to understand their functions and design new molecules. Current algorithms of RNA tertiary structure prediction give satisfactory accuracy only for small size and simple topology and many of them need manual manipulation. Here, we present an automated and fast program, 3dRNA, for RNA tertiary structure prediction with reasonable accuracy for RNAs of larger size and complex topology.

Quantifiable Assessment of SWNT Dispersion in Polymer Composites

NASA Technical Reports Server (NTRS)

Park, Cheol; Kim, Jae-Woo; Wise, Kristopher E.; Working, Dennis; Siochi, Mia; Harrison, Joycelyn; Gibbons, Luke; Siochi, Emilie J.; Lillehei, Peter T.; Cantrell, Sean;

Small Scaffolds, Big Potential: Developing Miniature Proteins as Therapeutic Agents.

PubMed

Holub, Justin M

2017-09-01

Preclinical Research Miniature proteins are a class of oligopeptide characterized by their short sequence lengths and ability to adopt well-folded, three-dimensional structures. Because of their biomimetic nature and synthetic tractability, miniature proteins have been used to study a range of biochemical processes including fast protein folding, signal transduction, catalysis and molecular transport. Recently, miniature proteins have been gaining traction as potential therapeutic agents because their small size and ability to fold into defined tertiary structures facilitates their development as protein-based drugs. This research overview discusses emerging developments involving the use of miniature proteins as scaffolds to design novel therapeutics for the treatment and study of human disease. Specifically, this review will explore strategies to: (i) stabilize miniature protein tertiary structure; (ii) optimize biomolecular recognition by grafting functional epitopes onto miniature protein scaffolds; and (iii) enhance cytosolic delivery of miniature proteins through the use of cationic motifs that facilitate endosomal escape. These objectives are discussed not only to address challenges in developing effective miniature protein-based drugs, but also to highlight the tremendous potential miniature proteins hold for combating and understanding human disease. Drug Dev Res 78 : 268-282, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

The external Rif of Morocco and its hydrocarbon potential

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

Jobidon, G.; Dakki, M.

1993-09-01

The Rif domain is a structurally complex area consisting of nappes and thrust sheets caused by the collision of the Eurasian and African plates during the Tertiary period. The structural complexity decreases southwardly. Autochthonous members are found only along the southern and southwestern periphery, while the northern units are autochthonous (internal Rif and mesorif). Recently acquired geophysical and geochemical data provide an improved understanding of the area and put the hydrocarbon potential of the prerif (south Rif) and the Rharb basin (southern foreland basin) in a new exploration perspective. The Rharb basin has a Cretaceous-to-Tertiary sedimentary evolution, with its maximummore » subsidence occurring during the Tortonian-to-Messinian with the emplacement of a thick olistrostrome (prerif nappe). Biogenic gas is found in the neritic postnappe Tortonian sediments, while a prenappe Cretaceous play now appears as a strong hydrocarbon potential. The Prerif Rides, which are separated from the Gharb basin by the northeast-southwest Sidi-Fili fault trend, are the structural consequence of salt tectonics within the Alpine compression system. Oil production occurred in thrusted Jurassic carbonates and fractured metamorphic Paleozoic rocks. The hydrocarbon potential of newly defined prospects in this area are still untapped.« less

Regional frontier exploration in Sinu basin, northwestern Colombia

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

Lindberg, F.A.; Ellis, J.M.; Dekker, L.L.

1989-03-01

In 1983, Gulf and Ecopetrol undertook a regional hydrocarbon evaluation of northwestern Colombia, during the course of which much of the Sinu basin was mapped by field geologists aided by low-altitude aerial photographs. Additional seismic and airborne radar data were acquired to assist in developing a regional structural model. The dominant structures of the Sinu basin were produced by westward-vergent thrust faults, which are offset on the order of 10 to 20 km by northwest-southeast-trending compartmental faults. Numerous mud volcanos are surface expressions of overpressured shales, which migrate upward along both thrust and strike-slip faults. Thrust faults are expressed, onmore » the surface, by steep-sided, asymmetrical anticlines, which are separated by broad synclines filled with clastics shed during Tertiary thrusting. The extremely thick section of Tertiary sediments is dominated by shale but contains some potential reservoir sandstones. These resistive sandstones could be accurately mapped on the radar imagery and projected into the subsurface allowing traps to be better defined. Combining field geology with geologic interpretation of aerial photographs and radar images was very effective in developing a regional structural framework of the Sinu basin.« less

Structural alignment of protein descriptors - a combinatorial model.

PubMed

Antczak, Maciej; Kasprzak, Marta; Lukasiak, Piotr; Blazewicz, Jacek

2016-09-17

Structural alignment of proteins is one of the most challenging problems in molecular biology. The tertiary structure of a protein strictly correlates with its function and computationally predicted structures are nowadays a main premise for understanding the latter. However, computationally derived 3D models often exhibit deviations from the native structure. A way to confirm a model is a comparison with other structures. The structural alignment of a pair of proteins can be defined with the use of a concept of protein descriptors. The protein descriptors are local substructures of protein molecules, which allow us to divide the original problem into a set of subproblems and, consequently, to propose a more efficient algorithmic solution. In the literature, one can find many applications of the descriptors concept that prove its usefulness for insight into protein 3D structures, but the proposed approaches are presented rather from the biological perspective than from the computational or algorithmic point of view. Efficient algorithms for identification and structural comparison of descriptors can become crucial components of methods for structural quality assessment as well as tertiary structure prediction. In this paper, we propose a new combinatorial model and new polynomial-time algorithms for the structural alignment of descriptors. The model is based on the maximum-size assignment problem, which we define here and prove that it can be solved in polynomial time. We demonstrate suitability of this approach by comparison with an exact backtracking algorithm. Besides a simplification coming from the combinatorial modeling, both on the conceptual and complexity level, we gain with this approach high quality of obtained results, in terms of 3D alignment accuracy and processing efficiency. All the proposed algorithms were developed and integrated in a computationally efficient tool descs-standalone, which allows the user to identify and structurally compare descriptors of biological molecules, such as proteins and RNAs. Both PDB (Protein Data Bank) and mmCIF (macromolecular Crystallographic Information File) formats are supported. The proposed tool is available as an open source project stored on GitHub ( https://github.com/mantczak/descs-standalone ).

Secondary structure encodes a cooperative tertiary folding funnel in the Azoarcus ribozyme

PubMed Central

Mustoe, Anthony M.; Al-Hashimi, Hashim M.; Brooks, Charles L.

2016-01-01

A requirement for specific RNA folding is that the free-energy landscape discriminate against non-native folds. While tertiary interactions are critical for stabilizing the native fold, they are relatively non-specific, suggesting additional mechanisms contribute to tertiary folding specificity. In this study, we use coarse-grained molecular dynamics simulations to explore how secondary structure shapes the tertiary free-energy landscape of the Azoarcus ribozyme. We show that steric and connectivity constraints posed by secondary structure strongly limit the accessible conformational space of the ribozyme, and that these so-called topological constraints in turn pose strong free-energy penalties on forming different tertiary contacts. Notably, native A-minor and base-triple interactions form with low conformational free energy, while non-native tetraloop/tetraloop–receptor interactions are penalized by high conformational free energies. Topological constraints also give rise to strong cooperativity between distal tertiary interactions, quantitatively matching prior experimental measurements. The specificity of the folding landscape is further enhanced as tertiary contacts place additional constraints on the conformational space, progressively funneling the molecule to the native state. These results indicate that secondary structure assists the ribozyme in navigating the otherwise rugged tertiary folding landscape, and further emphasize topological constraints as a key force in RNA folding. PMID:26481360

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

Trevena, A.S.; Varga, R.J.; Collins, I.D.

Salin basin of central Myanmar is a tertiary fore-arc basin that extends over 10,000 mi{sup 2} and contains 30,000+ ft of siliciclastic rocks. In the western Salin basin, Tertiary deltaic and fluvial formations contain thousands of feet of lithic sandstones that alternate with transgressive shallow marine shales. Facies and paleocurrent studies indicate deposition by north-to-south prograding tidal deltas and associated fluvial systems in a semi-restricted basin. Presence of serpentinite and volcanic clasts in Tertiary sandstones may imply that the basin was bounded to the east by the volcanic arc and to the west by a fore-arc accretionary ridge throughout muchmore » of the Cenozoic. Salin basin is currently defined by a regional north/south-trending syncline with uplifts along the eastern and western margins. Elongate folds along the eastern basin margin verge to the east and lie above the reverse faults that dip west; much of Myanmar's present hydrocarbon production is from these structures. Analogous structures occur along the western margin, but verge to the west and are associated with numerous hydrocarbon seeps and hand-dug wells. These basin-bounding structures are the result of fault-propagation folding. In the western Salin basin, major detachments occur within the shaly Tabyin and Laungshe formations. Fault ramps propagated through steep forelimbs on the western sides of the folds, resulting in highly asymmetric footwall synclines. Stratigraphic and apatite fission track data are consistent with dominantly Plio-Pleistocene uplift, with limited uplift beginning approximately 10 Ma. Paleostress analysis of fault/slickenside data indicates that fold and thrust structures formed during regional east/west compression and are not related in any simple way to regional transpression as suggested by plate kinematics.« less

Tectonic framework of Turkish sedimentary basins

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

Yilmaz, P.O.

1988-08-01

Turkey's exploration potential primarily exists in seven onshore (Southeast Turkey platform, Tauride platform, Pontide platform, East Anatolian platform, Interior, Trace, and Adana) basins and four offshore (Black Sea, Marmara Sea, Aegean Sea, and Mediterranean Sea) regional basins formed during the Mesozoic and Tertiary. The Mesozoic basins are the onshore basins: Southeast Turkey, Tauride, Pontide, East Anatolian, and Interior basins. Due to their common tectonic heritage, the southeast Turkey and Tauride basins have similar source rocks, structural growth, trap size, and structural styles. In the north, another Mesozoic basin, the Pontide platform, has a much more complex history and very littlemore » in common with the southerly basins. The Pontide has two distinct parts; the west has Paleozoic continental basement and the east is underlain by island-arc basement of Jurassic age. The plays are in the upper Mesozoic rocks in the west Pontide. The remaining Mesozoic basins of the onshore Interior and East Anatolian basins are poorly known and very complex. Their source, reservoir, and seal are not clearly defined. The basins formed during several orogenic phases in mesozoic and Tertiary. The Cenozoic basins are the onshore Thrace and Adana basins, and all offshore regional basins formed during Miocene extension. Further complicating the onshore basins evolution is the superposition of Cenozoic basins and Mesozoic basins. The Thrace basin in the northwest and Adana basin in the south both originate from Tertiary extension over Tethyan basement and result in a similar source, reservoir, and seal. Local strike-slip movement along the North Anatolian fault modifies the Thrace basin structures, influencing its hydrocarbon potential.« less

[Decomposition model of energy-related carbon emissions in tertiary industry for China].

PubMed

Lu, Yuan-Qing; Shi, Jun

2012-07-01

Tertiary industry has been developed in recent years. And it is very important to find the factors influenced the energy-related carbon emissions in tertiary industry. A decomposition model of energy-related carbon emissions for China is set up by adopting logarithmic mean weight Divisia method based on the identity of carbon emissions. The model is adopted to analyze the influence of energy structure, energy efficiency, tertiary industry structure and economic output to energy-related carbon emissions in China from 2000 to 2009. Results show that the contribution rate of economic output and energy structure to energy-related carbon emissions increases year by year. Either is the contribution rate of energy efficiency or the tertiary industry restraining to energy-related carbon emissions. However, the restrain effect is weakening.

Halitosis amongst students in tertiary institutions in Lagos state.

PubMed

Arinola, J E; Olukoju, O O

2012-12-01

Halitosis is defined as a noticeable unpleasant odor from the mouth. It is a medico-social problem that affects a significant number of people around the world. Research reveals that nearly 50% of the adult population has halitosis. To determine level of awareness of halitosis and prevalence of the condition amongst students in tertiary institutions as a baseline survey. For this project, 100 students from three tertiary institutions in Lagos state were chosen: University of Lagos, Lagos State University, Ojo campus and Yaba College of Technology. A semi-structured questionnaire and practical testing/diagnostic tool were utilized. Data collected was collated and analyzed using Microsoft Excel 2007 and SPSS statistical software. Most of the respondents were single and Christian. Level of awareness of halitosis was high. Results showed that 15%, 2% and 22% from UNILAG, LASU and YCT respectively said they had halitosis. Using the diagnostic tool, 6%, 8% and 2% respectively were positive for halitosis. There is high level of awareness of halitosis among the respondents. The prevalence of the disorder is low, however, it is recommended that enlightenment campaigns be mounted in schools to improve level of awareness and treatment seeking.

Application of Tryptophan Fluorescence Bandwidth-Maximum Plot in Analysis of Monoclonal Antibody Structure.

PubMed

Huang, Cheng-Yen; Hsieh, Ming-Ching; Zhou, Qinwei

2017-04-01

Monoclonal antibodies have become the fastest growing protein therapeutics in recent years. The stability and heterogeneity pertaining to its physical and chemical structures remain a big challenge. Tryptophan fluorescence has been proven to be a versatile tool to monitor protein tertiary structure. By modeling the tryptophan fluorescence emission envelope with log-normal distribution curves, the quantitative measure can be exercised for the routine characterization of monoclonal antibody overall tertiary structure. Furthermore, the log-normal deconvolution results can be presented as a two-dimensional plot with tryptophan emission bandwidth vs. emission maximum to enhance the resolution when comparing samples or as a function of applied perturbations. We demonstrate this by studying four different monoclonal antibodies, which show the distinction on emission bandwidth-maximum plot despite their similarity in overall amino acid sequences and tertiary structures. This strategy is also used to demonstrate the tertiary structure comparability between different lots manufactured for one of the monoclonal antibodies (mAb2). In addition, in the unfolding transition studies of mAb2 as a function of guanidine hydrochloride concentration, the evolution of the tertiary structure can be clearly traced in the emission bandwidth-maximum plot.

PAT: predictor for structured units and its application for the optimization of target molecules for the generation of synthetic antibodies.

PubMed

Jeon, Jouhyun; Arnold, Roland; Singh, Fateh; Teyra, Joan; Braun, Tatjana; Kim, Philip M

2016-04-01

The identification of structured units in a protein sequence is an important first step for most biochemical studies. Importantly for this study, the identification of stable structured region is a crucial first step to generate novel synthetic antibodies. While many approaches to find domains or predict structured regions exist, important limitations remain, such as the optimization of domain boundaries and the lack of identification of non-domain structured units. Moreover, no integrated tool exists to find and optimize structural domains within protein sequences. Here, we describe a new tool, PAT ( http://www.kimlab.org/software/pat ) that can efficiently identify both domains (with optimized boundaries) and non-domain putative structured units. PAT automatically analyzes various structural properties, evaluates the folding stability, and reports possible structural domains in a given protein sequence. For reliability evaluation of PAT, we applied PAT to identify antibody target molecules based on the notion that soluble and well-defined protein secondary and tertiary structures are appropriate target molecules for synthetic antibodies. PAT is an efficient and sensitive tool to identify structured units. A performance analysis shows that PAT can characterize structurally well-defined regions in a given sequence and outperforms other efforts to define reliable boundaries of domains. Specially, PAT successfully identifies experimentally confirmed target molecules for antibody generation. PAT also offers the pre-calculated results of 20,210 human proteins to accelerate common queries. PAT can therefore help to investigate large-scale structured domains and improve the success rate for synthetic antibody generation.

[Changes in the secondary and tertiary structure of serum albumin in interactions with ligands of various structures].

PubMed

Trinus, F P; Braver-Chernobul'skaia, B S; Luĭk, A I; Boldeskul, A E; Velichko, A N

1984-01-01

High affinity interactions between blood serum albumin and five substances of various chemical structure, exhibiting distinct physiological activity, were accompanied by alterations in the protein tertiary structure, while the albumin secondary structure was involved in conformational transformation after less effective affinity binding.

Geologic Map of Prescott National Forest and the Headwaters of the Verde River, Yavapai and Coconino Counties, Arizona

USGS Publications Warehouse

DeWitt, Ed; Langenheim, V.E.; Force, Eric; Vance, R.K.; Lindberg, P.A.; Driscoll, R.L.

2008-01-01

This 1:100,000-scale digital geologic map details the complex Early Proterozoic metavolcanic and plutonic basement of north-central Arizona; shows the mildly deformed cover of Paleozoic rocks; reveals where Laramide to mid-Tertiary plutonic rocks associated with base- and precious-metals deposits are exposed; subdivides the Tertiary volcanic rocks according to chemically named units; and maps the Pliocene to Miocene fill of major basins. Associated digital files include more than 1,300 geochemical analyses of all rock units; 1,750 logs of water wells deeper than 300 feet; and interpreted logs of 300 wells that define the depth to basement in major basins. Geophysically interpreted buried features include normal faults defining previous unknown basins, mid-Tertiary intrusive rocks, and half-grabens within shallow bains.

Exploring the relevance of gas-phase structures to biology: cold ion spectroscopy of the decapeptide neurokinin A.

PubMed

Pereverzev, A Y; Boyarkin, O V

2017-02-01

Linking the intrinsic tertiary structures of biomolecules to their native geometries is a central prerequisite for making gas-phase studies directly relevant to biology. The isolation of molecules in the gas phase eliminates hydrophilic interactions with solvents, to some extent mimicking a hydrophobic environment. Intrinsic structures therefore may resemble native ones for peptides that in vivo reside in a hydrophobic environment (e.g., binding pockets of receptors). In this study, we investigate doubly protonated neurokinin A (NKA) using IR-UV double resonance cold ion spectroscopy and find only five conformers of this decapeptide in the gas phase. In contrast, NMR data show that in aqueous solutions, NKA exhibits high conformational heterogeneity, which reduces to a few well-defined structures in hydrophobic micelles. Do the gas-phase structures of NKA resemble these native structures? The IR spectra reported here allow the validation of future structural calculations that may answer this question.

Patterns of Debate in Tertiary Level Asynchronous Text-Based Conferencing

ERIC Educational Resources Information Center

Coffin, Caroline; Painter, Clare; Hewings, Ann

2005-01-01

Argumentation can be defined at different levels and serve different purposes, but its role in knowledge understanding and construction has given it a central place in education, particularly at tertiary level. The advent of computer-supported text-based conferences has created new sites where such educational dialogues can take place, but the…

Categorising E-Learning

ERIC Educational Resources Information Center

Wilson, Amy D.

2012-01-01

Categorising e-learning is almost as problematic as defining the term. In an attempt to quantify/qualify the level of e-learning use in the tertiary sector in New Zealand, the Ministry of Education (MoE) established a classification system for courses in the tertiary sector. The value of this tool was disputed, and a new system was proposed but…

Reverse Polarity Magnetized Melt Rocks from the Cretaceous/Tertiary Chicxulub Structure, Yucatan Peninsula, Mexico

NASA Technical Reports Server (NTRS)

Urrutia-Fucugauchi, J.; Marin, Luis; Sharpton, Virgil L.

1994-01-01

We report paleomagnetic results for core samples of the breccia and andesitic rocks recovered from the Yucatan-6 Petrolcos Mexicanos exploratory well within the Chicxulub structure (about 60 km SSW from its center), northern Yucatan, Mexico. A previous study has shown that the rocks studied contain high iridium levels and shocked breccia clasts and an Ar/Ar date of 65.2 +/- 0.4 Ma. Andesitic rocks are characterized by stable single-component magnetizations with a mean inclination of -42.6 deg +/- 2.4 deg. Breccias present a complex paleomagnetic record characterized by multivectorial magnetizations with widely different initial NRM inclinations. However, after alternating field demagnetization, well defined characteristic components with upward inclinations are defined. IRM acquisition experiments, comparison of IRM and NRM coercivity spectra and the single component magnetization of the andesitic rocks indicate the occurrence of iron-rich titanomagnetites of single or pseudo-single domain states as the dominant magnetic carriers. Mean inclinations from the andesitic rocks and most of the breccia samples give a mean inclination of about -40 deg to -45 deg, indicating a reverse polarity for the characteristic magnetization that is consistent with geomagnetic chron 29R, which spans the Cretaceous/Tertiary (K/T) boundary. The inclination is also consistent with the expected value (and corresponding paleolatitude) for the site estimated from the reference polar wander curve for North America. We suggest that the characteristic magnetizations for the andesitic and breccia rocks are the result of shock heating at the time of formation of the impact structure and that the age, polarity and pateolatitude are consistent with a time at the K/T boundary.

Generic Features of Tertiary Chromatin Structure as Detected in Natural Chromosomes

PubMed Central

Müller, Waltraud G.; Rieder, Dietmar; Kreth, Gregor; Cremer, Christoph; Trajanoski, Zlatko; McNally, James G.

2004-01-01

Knowledge of tertiary chromatin structure in mammalian interphase chromosomes is largely derived from artificial tandem arrays. In these model systems, light microscope images reveal fibers or beaded fibers after high-density targeting of transactivators to insertional domains spanning several megabases. These images of fibers have lent support to chromonema fiber models of tertiary structure. To assess the relevance of these studies to natural mammalian chromatin, we identified two different ∼400-kb regions on human chromosomes 6 and 22 and then examined light microscope images of interphase tertiary chromatin structure when the regions were transcriptionally active and inactive. When transcriptionally active, these natural chromosomal regions elongated, yielding images characterized by a series of adjacent puncta or “beads”, referred to hereafter as beaded images. These elongated structures required transcription for their maintenance. Thus, despite marked differences in the density and the mode of transactivation, the natural and artificial systems showed similarities, suggesting that beaded images are generic features of transcriptionally active tertiary chromatin. We show here, however, that these images do not necessarily favor chromonema fiber models but can also be explained by a radial-loop model or even a simple nucleosome affinity, random-chain model. Thus, light microscope images of tertiary structure cannot distinguish among competing models, although they do impose key constraints: chromatin must be clustered to yield beaded images and then packaged within each cluster to enable decondensation into adjacent clusters. PMID:15485905

Sub-crop geologic map of pre-Tertiary rocks in the Yucca Flat and northern Frenchman Flat areas, Nevada Test Site, southern Nevada

USGS Publications Warehouse

Cole, James C.; Harris, Anita G.; Wahl, Ronald R.

1997-01-01

This map displays interpreted structural and stratigraphic relations among the Paleozoic and older rocks of the Nevada Test Site region beneath the Miocene volcanic rocks and younger alluvium in the Yucca Flat and northern Frenchman Flat basins. These interpretations are based on a comprehensive examination and review of data for more than 77 drillholes that penetrated part of the pre-Tertiary basement beneath these post-middle Miocene structural basins. Biostratigraphic data from conodont fossils were newly obtained for 31 of these holes, and a thorough review of all prior microfossil paleontologic data is incorporated in the analysis. Subsurface relationships are interpreted in light of a revised regional geologic framework synthesized from detailed geologic mapping in the ranges surrounding Yucca Flat, from comprehensive stratigraphic studies in the region, and from additional detailed field studies on and around the Nevada Test Site.All available data indicate the subsurface geology of Yucca Flat is considerably more complicated than previous interpretations have suggested. The western part of the basin, in particular, is underlain by relics of the eastward-vergent Belted Range thrust system that are folded back toward the west and thrust by local, west-vergent contractional structures of the CP thrust system. Field evidence from the ranges surrounding the north end of Yucca Flat indicate that two significant strike-slip faults track southward beneath the post-middle Miocene basin fill, but their subsurface traces cannot be closely defined from the available evidence. In contrast, the eastern part of the Yucca Flat basin is interpreted to be underlain by a fairly simple north-trending, broad syncline in the pre-Tertiary units. Far fewer data are available for the northern Frenchman Flat basin, but regional analysis indicates the pre- Tertiary structure there should also be relatively simple and not affected by thrusting.This new interpretation has implications for ground water flow through pre-Tertiary rocks beneath the Yucca Flat and northern Frenchman Flat areas, and has consequences for ground water modeling and model validation. Our data indicate that the Mississippian Chainman Shale is not a laterally extensive confining unit in the western part of the basin because it is folded back onto itself by the convergent structures of the Belted Range and CP thrust systems. Early and Middle Paleozoic limestone and dolomite are present beneath most of both basins and, regardless of structural complications, are interpreted to form a laterally continuous and extensive carbonate aquifer. Structural culmination that marks the French Peak accommodation zone along the topographic divide between the two basins provides a lateral pathway through highly fractured rock between the volcanic aquifers of Yucca Flat and the regional carbonate aquifer. This pathway may accelerate the migration of ground-water contaminants introduced by underground nuclear testing toward discharge areas beyond the Nevada Test Site boundaries. Predictive three-dimensional models of hydrostratigraphic units and ground-water flow in the pre-Tertiary rocks of subsurface Yucca Flat are likely to be unrealistic due to the extreme structural complexities. The interpretation of hydrologic and geochemical data obtained from monitoring wells will be difficult to extrapolate through the flow system until more is known about the continuity of hydrostratigraphic units.

Tertiary structure-related activity of tick defensin (persulcatusin) in the taiga tick, Ixodes persulcatus.

PubMed

Isogai, Emiko; Isogai, Hiroshi; Okumura, Kazuhiko; Hori, Hatsuhiro; Tsuruta, Hiroki; Kurebayashi, Yoichi

2011-01-01

Defensins are small cysteine-rich cationic proteins found in both vertebrates and invertebrates constituting the front line of host innate immunity. To examine the importance of the tertiary structure of tick defensin in its antimicrobial activity, we synthesized two types of the peptides with tertiary structure or primary one on basis of the information of the sequence in the defensin originated from the taiga tick, Ixodes persulcatus. Chemically synthesized peptides were used to investigate the activity spectrum against Staphylococcus aureus, Borrelia garinii and flora-associated bacteria. Both synthetic peptides showed antimicrobial activity against S. aureus in short-time killing within 1 h, but they do not show the activity against B. garinii, Stenotrophomonas maltophila and Bacillus spp., which were frequently isolated from the midgut of I. persulcatus. The teriary structure brought more potent activity to S. aureus than primary one in short-time killing. We also examined its antimicrobial activity by evaluation of growth inhibition in the presence of the synthetic peptides. Minimum inhibitory concentration (MIC) was ranged from 1.2 to 5.0 μg/ml in tertiary peptide and from 10 to 40 μg/ml in primary peptide, when 10 strains of S. aureus were used. From the curve of cumulative inhibition rates, MIC50 (MIC which half of the strains showed) to S. aureus is about 1.2 μg/ml in the peptide with tertiary structure and about 10 μg/ml in the linear one. Corynebacterium renale is 10 times or more sensitive to tertiary peptide than primary one. In conclusion, the presence of 3 disulfide bridges, which stabilize the molecule and maintain the tertiary structure, is considered to have an effect on their antimicrobial activities against Gram-positive bacteria such as S. aureus.

Quantitative tests of a reconstitution model for RNA folding thermodynamics and kinetics.

PubMed

Bisaria, Namita; Greenfeld, Max; Limouse, Charles; Mabuchi, Hideo; Herschlag, Daniel

2017-09-12

Decades of study of the architecture and function of structured RNAs have led to the perspective that RNA tertiary structure is modular, made of locally stable domains that retain their structure across RNAs. We formalize a hypothesis inspired by this modularity-that RNA folding thermodynamics and kinetics can be quantitatively predicted from separable energetic contributions of the individual components of a complex RNA. This reconstitution hypothesis considers RNA tertiary folding in terms of ΔG align , the probability of aligning tertiary contact partners, and ΔG tert , the favorable energetic contribution from the formation of tertiary contacts in an aligned state. This hypothesis predicts that changes in the alignment of tertiary contacts from different connecting helices and junctions (ΔG HJH ) or from changes in the electrostatic environment (ΔG +/- ) will not affect the energetic perturbation from a mutation in a tertiary contact (ΔΔG tert ). Consistent with these predictions, single-molecule FRET measurements of folding of model RNAs revealed constant ΔΔG tert values for mutations in a tertiary contact embedded in different structural contexts and under different electrostatic conditions. The kinetic effects of these mutations provide further support for modular behavior of RNA elements and suggest that tertiary mutations may be used to identify rate-limiting steps and dissect folding and assembly pathways for complex RNAs. Overall, our model and results are foundational for a predictive understanding of RNA folding that will allow manipulation of RNA folding thermodynamics and kinetics. Conversely, the approaches herein can identify cases where an independent, additive model cannot be applied and so require additional investigation.

Thermodynamics and kinetics of RNA tertiary structure formation in the junctionless hairpin ribozyme.

PubMed

White, Neil A; Hoogstraten, Charles G

2017-09-01

The hairpin ribozyme consists of two RNA internal loops that interact to form the catalytically active structure. This docking transition is a rare example of intermolecular formation of RNA tertiary structure without coupling to helix annealing. We have used temperature-dependent surface plasmon resonance (SPR) to characterize the thermodynamics and kinetics of RNA tertiary structure formation for the junctionless form of the ribozyme, in which loops A and B reside on separate molecules. We find docking to be strongly enthalpy-driven and to be accompanied by substantial activation barriers for association and dissociation, consistent with the structural reorganization of both internal loops upon complex formation. Comparisons with the parallel analysis of a ribozyme variant carrying a 2'-O-methyl modification at the self-cleavage site and with published data in other systems reveal a surprising diversity of thermodynamic signatures, emphasizing the delicate balance of contributions to the free energy of formation of RNA tertiary structure. Copyright © 2017 Elsevier B.V. All rights reserved.

Lead-isotopic data from sulfide minerals from the Cascade Range, Oregon and Washington

USGS Publications Warehouse

Church, S.E.; LeHuray, A.P.; Grant, A.R.; Delevaux, M.H.; Gray, J.E.

1986-01-01

Lead-isotopic studies of mineral deposits associated with Tertiary plutons found in the Cascade Range of Oregon and Washington demonstrate a rather uniform isotopic composition in various sulfide minerals ( 206Pb 204Pb = 18.84 to 19.05; 207Pb 204Pb = 15.57 to 15.62; 208Pb 204Pb = 38.49 to 38.74), show less variation than data from the volcanic rocks of the Cascade Range and fall within the mixing array defined by the MORB regression line and continental sediments. An evaluation of the role of crustal assimilation by hydrothermal convection during emplacement was made on five sulfide deposits associated with a single composite batholith, the Cloudy Pass pluton. The Pb-isotopic data and mass balance calculations suggest that only minor amounts of the lead were derived from the overlying Precambrian (?) Swakane Biotite Gneiss during emplacement. The bulk of the metal that occurs in sulfide deposits in the Cascade mineral belt appears to have been derived from subducted continental detritus. The variation of the Pb-isotopic signature of Sulfides from specific districts or deposits suggests that there is a correlation with age and structure of the crust. 206Pb 204Pb is greater than 18.92 in northern Washington and southern Oregon where deposits have intruded Mesozoic or older crust. However, the ore deposits between the northern Oregon border and central Oregon, south of Eugene, have intruded younger crust composed largely of mafic and andesitic volcanic rocks and 206Pb 204Pb lies between 18.84 and 18.92. This region, previously called the Columbia embayment, appears to be underlain by Tertiary volcanic rocks. Lead-isotopic data may be used to define the boundaries between discontinuous blocks of Mesozoic crust and Tertiary volcanic cover. ?? 1986.

Kinetic and thermodynamic framework for P4-P6 RNA reveals tertiary motif modularity and modulation of the folding preferred pathway

PubMed Central

Bisaria, Namita; Greenfeld, Max; Limouse, Charles; Pavlichin, Dmitri S.; Mabuchi, Hideo; Herschlag, Daniel

2016-01-01

The past decade has seen a wealth of 3D structural information about complex structured RNAs and identification of functional intermediates. Nevertheless, developing a complete and predictive understanding of the folding and function of these RNAs in biology will require connection of individual rate and equilibrium constants to structural changes that occur in individual folding steps and further relating these steps to the properties and behavior of isolated, simplified systems. To accomplish these goals we used the considerable structural knowledge of the folded, unfolded, and intermediate states of P4-P6 RNA. We enumerated structural states and possible folding transitions and determined rate and equilibrium constants for the transitions between these states using single-molecule FRET with a series of mutant P4-P6 variants. Comparisons with simplified constructs containing an isolated tertiary contact suggest that a given tertiary interaction has a stereotyped rate for breaking that may help identify structural transitions within complex RNAs and simplify the prediction of folding kinetics and thermodynamics for structured RNAs from their parts. The preferred folding pathway involves initial formation of the proximal tertiary contact. However, this preference was only ∼10 fold and could be reversed by a single point mutation, indicating that a model akin to a protein-folding contact order model will not suffice to describe RNA folding. Instead, our results suggest a strong analogy with a modified RNA diffusion-collision model in which tertiary elements within preformed secondary structures collide, with the success of these collisions dependent on whether the tertiary elements are in their rare binding-competent conformations. PMID:27493222

Structure of the Espanola Basin, Rio Grande Rift, New Mexico, from SAGE seismic and gravity data

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

Ferguson, J.F.; Baldridge, W.S.; Braile, L.W.

1995-04-01

Seismic and gravity data, acquired by the SAGE program over the past twelve years, are used to define the geometry of the Espanola basin and the extent of pre-Tertiary sedimentary rocks. The Paleozoic and Mesozoic units have been thinned and removed during Laramide uplift in an area now obscured by the younger rift basin. The Espanola basin is generally a shallow, asymmetric transitional structure between deeper, better developed basins to the northeast and southwest. The gravity data indicate the presence of three narrow, but deep, structural lows arrayed along the Embudo/Pajarito fault system. These sub-basins seem to be younger thanmore » the faults on the basin margins. This apparent focussing of deformation in the later history of the basin may be a response to changes in regional stress or more local accommodation of the rift extension. Future work is planned to develop seismic data over one of these sub-basins, the Velarde graben, and to better define the gravity map in order to facilitate three-dimensional modeling.« less

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

Freezing-Induced Perturbation of Tertiary Structure of a Monoclonal Antibody

PubMed Central

LIU, LU; BRAUN, LATOYA JONES; WANG, WEI; RANDOLPH, THEODORE W.; CARPENTER, JOHN F.

2014-01-01

We studied the effects of pH and solution additives on freezing-induced perturbations in the tertiary structure of a monoclonal antibody (mAb) by intrinsic tryptophan fluorescence spectroscopy. In general, freezing caused perturbations in the tertiary structure of the mAb, which were reversible or irreversible depending on the pH or excipients present in the formulation. Protein aggregation occurred in freeze–thawed samples in which perturbations of the tertiary structure were observed, but the levels of protein aggregates formed were not proportional to the degree of structural perturbation. Protein aggregation also occurred in freeze–thawed samples without obvious structural perturbations, most likely because of freeze concentration of protein and salts, and thus reduced protein colloidal stability. Therefore, freezing-induced protein aggregation may or may not first involve the perturbation of its native structure, followed by the assembly processes to form aggregates. Depending on the solution conditions, either step can be rate limiting. Finally, this study demonstrates the potential of fluorescence spectroscopy as a valuable tool for screening therapeutic protein formulations subjected to freeze–thaw stress. PMID:24832730

The roles of tertiary amine structure, background organic matter and chloramine species on NDMA formation.

PubMed

Selbes, Meric; Kim, Daekyun; Ates, Nuray; Karanfil, Tanju

2013-02-01

N-nitrosodimethylamine (NDMA), a probable human carcinogen, is a disinfection by-product that has been detected in chloraminated and chlorinated drinking waters and wastewaters. Formation mechanisms and precursors of NDMA are still not well understood. The main objectives of this study were to systematically investigate (i) the effect of tertiary amine structure, (ii) the effect of background natural organic matter (NOM), and (iii) the roles of mono vs. dichloramine species on the NDMA formation. Dimethylamine (DMA) and 20 different tertiary aliphatic and aromatic amines were carefully examined based on their functional groups attached to the basic DMA structure. The wide range (0.02-83.9%) of observed NDMA yields indicated the importance of the structure of tertiary amines, and both stability and electron distribution of the leaving group of tertiary amines on NDMA formation. DMA associated with branched alkyl groups or benzyl like structures having only one carbon between the ring and DMA structure consistently gave higher NDMA yields. Compounds with electron withdrawing groups (EWG) reacted preferentially with monochloramine, whereas compounds with electron donating group (EDG) showed tendency to react with dichloramine to form NDMA. When the selected amines were present in NOM solutions, NDMA formation increased for compounds with EWG while decreased for compounds with EDG. This impact was attributed to the competitions between NOM and amines for chloramine species. The results provided additional information to the commonly accepted mechanism for NDMA formation including chloramine species reacting with tertiary amines and the role of the leaving group on overall NDMA conversion. Copyright © 2012 Elsevier Ltd. All rights reserved.

Entropy-Driven Folding of an RNA Helical Junction: An Isothermal Titration Calorimetric Analysis of the Hammerhead Ribozyme†

PubMed Central

Mikulecky, Peter J.; Takach, Jennifer C.; Feig, Andrew L.

2008-01-01

Helical junctions are extremely common motifs in naturally occurring RNAs, but little is known about the thermodynamics that drive their folding. Studies of junction folding face several challenges: non-two-state folding behavior, superposition of secondary and tertiary structural energetics, and drastically opposing enthalpic and entropic contributions to folding. Here we describe a thermodynamic dissection of the folding of the hammerhead ribozyme, a three-way RNA helical junction, by using isothermal titration calorimetry of bimolecular RNA constructs. By using this method, we show that tertiary folding of the hammerhead core occurs with a highly unfavorable enthalpy change, and is therefore entropically driven. Furthermore, the enthalpies and heat capacities of core folding are the same whether supported by monovalent or divalent ions. These properties appear to be general to the core sequence of bimolecular hammerhead constructs. We present a model for the ion-induced folding of the hammerhead core that is similar to those advanced for the folding of much larger RNAs, involving ion-induced collapse to a structured, non-native state accompanied by rearrangement of core residues to produce the native fold. In agreement with previous enzymological and structural studies, our thermodynamic data suggest that the hammerhead structure is stabilized in vitro predominantly by diffusely bound ions. Our approach addresses several significant challenges that accompany the study of junction folding, and should prove useful in defining the thermodynamic determinants of stability in these important RNA motifs. PMID:15134461

Dithiol amino acids can structurally shape and enhance the ligand-binding properties of polypeptides

NASA Astrophysics Data System (ADS)

Chen, Shiyu; Gopalakrishnan, Ranganath; Schaer, Tifany; Marger, Fabrice; Hovius, Ruud; Bertrand, Daniel; Pojer, Florence; Heinis, Christian

2014-11-01

The disulfide bonds that form between two cysteine residues are important in defining and rigidifying the structures of proteins and peptides. In polypeptides containing multiple cysteine residues, disulfide isomerization can lead to multiple products with different biological activities. Here, we describe the development of a dithiol amino acid (Dtaa) that can form two disulfide bridges at a single amino acid site. Application of Dtaas to a serine protease inhibitor and a nicotinic acetylcholine receptor inhibitor that contain disulfide constraints enhanced their inhibitory activities 40- and 7.6-fold, respectively. X-ray crystallographic and NMR structure analysis show that the peptide ligands containing Dtaas have retained their native tertiary structures. We furthermore show that replacement of two cysteines by Dtaas can avoid the formation of disulfide bond isomers. With these properties, Dtaas are likely to have broad application in the rational design or directed evolution of peptides and proteins with high activity and stability.

Quantification of the Thermodynamically Linked Quaternary and Tertiary Structural Stabilities of Transthyretin and its Disease-Associated Variants–the Relationship between Stability and Amyloidosis†

PubMed Central

Hurshman Babbes, Amy R.; Powers, Evan T.; Kelly, Jeffery W.

2009-01-01

Urea denaturation studies were carried out as a function of transthyretin (TTR) concentration to quantify the thermodynamically linked quaternary and tertiary structural stability and to better understand the relationship between mutant folding energetics and amyloid disease phenotype. Urea denaturation of TTR involves at least two equilibria—dissociation of tetramers into folded monomers, and monomer unfolding. To deal with the thermodynamic linkage of these equilibria, we analyzed concentration-dependent denaturation data by global fitting to an equation that simultaneously accounts for the two-step denaturation process. Using this method, the quaternary and tertiary structural stabilities of well-behaved TTR sequences, wild type (WT) TTR and the disease-associated variant V122I, were scrutinized. The V122I variant is linked to late onset familial amyloid cardiomyopathy, the most common familial TTR amyloid disease. V122I TTR exhibits a destabilized quaternary structure and a stable tertiary structure relative to WT TTR. Three other variants of TTR were also examined, L55P, V30M, and A25T TTR. The L55P mutation is associated with the most aggressive familial TTR amyloid disease. L55P TTR has a complicated denaturation pathway that includes dimers and trimers, and so globally fitting its concentration-dependent urea denaturation data yielded error-laden estimates of stability parameters. Nevertheless, it is clear that L55P TTR is substantially less stable than WT TTR, primarily because its tertiary structure is unstable, although its quaternary structure is destabilized as well. V30M is the most common mutation associated with neuropathic forms of TTR amyloid disease. V30M TTR is certainly destabilized relative to WT TTR, but like L55P TTR it has a complex denaturation pathway that cannot be fit to the aforementioned two-step denaturation model. Literature data suggest that V30M TTR has stable quaternary structure but unstable tertiary structure. The A25T mutant, associated with central nervous system amyloidosis, is highly aggregation-prone and exhibits drastically reduced quaternary and tertiary structural stability. The observed differences in stability amongst the disease-associated TTR variants highlight the complexity and the heterogeneity of TTR amyloid disease, an observation having important implications for the treatment of these diseases. PMID:18537267

Diversification of Tertiary Education in Switzerland.

ERIC Educational Resources Information Center

Crausaz, Roselyne

The structure of Switzerland's educational system is described including the types of secondary schools and/or courses and the system of tertiary education. Fields of study, types of institutions, and characteristics of tertiary education in Switzerland are discussed. The chapter on students covers admission procedures, trends in enrollment,…

Maps showing the distribution of uranium-deposit clusters in the Colorado Plateau uranium province

USGS Publications Warehouse

Finch, Warren I.

1991-01-01

The Colorado Palteau Uranium Province (CPUP) is defined by the distribution of uranium deposits, chiefly the sandstone-type, in upper Paleozoic and Mesozoic sedimentary rocks within the Colorado Plateau physiographic province (Granger and others, 1986).  The uranium province is bordered by widely distributed and mostly minor uranium deposits in Precambrian and Tertiary rocks and by outcrops of Tertiary extrusive and intrusive igneous rocks.  

Tertiary Gleason patterns and biochemical recurrence after prostatectomy: proposal for a modified Gleason scoring system.

PubMed

Trock, Bruce J; Guo, Charles C; Gonzalgo, Mark L; Magheli, Ahmed; Loeb, Stacy; Epstein, Jonathan I

2009-10-01

We investigated the relationship between the tertiary Gleason component in radical prostatectomy specimens and biochemical recurrence in what is to our knowledge the largest single institution cohort to date. We evaluated data on 3,230 men who underwent radical prostatectomy at our institution from 2000 to 2005. Tertiary Gleason component was defined as Gleason grade pattern 4 or greater for Gleason score 6 and Gleason grade pattern 5 for Gleason score 7 or 8. Biochemical recurrence curves for cancer with tertiary Gleason component were intermediate between those of cancer without a tertiary Gleason component in the same Gleason score category and cancer in the next higher Gleason score category. The only exception was that Gleason score 4 + 3 = 7 with a tertiary Gleason component behaved like Gleason score 8. The tertiary Gleason component independently predicted recurrence when factoring in radical prostatectomy Gleason score, radical prostatectomy stage and prostate specific antigen (HR 1.45, p = 0.029). Furthermore, the magnitude of the tertiary Gleason component effect on recurrence did not differ by Gleason score category (p = 0.593). Although the tertiary Gleason component is frequently included in pathology reports, it is routinely omitted in other situations, such as predictive nomograms, research studies and patient counseling. The current study adds to a growing body of evidence highlighting the importance of the tertiary Gleason component in radical prostatectomy specimens. Accordingly consideration should be given to a modified radical prostatectomy Gleason scoring system that incorporates tertiary Gleason component in intuitive fashion, including Gleason score 6, 6.5 (Gleason score 6 with tertiary Gleason component), 7 (Gleason score 3 + 4 = 7), 7.25 (Gleason score 3 + 4 = 7 with tertiary Gleason component), 7.5 (Gleason score 4 + 3), 8 (Gleason score 4 + 3 with tertiary Gleason component or Gleason score 8), 8.5 (Gleason score 8 with tertiary Gleason component), 9 (Gleason score 4 + 5 or 5 + 4) and 10.

Prelude and Fugue, predicting local protein structure, early folding regions and structural weaknesses.

PubMed

Kwasigroch, Jean Marc; Rooman, Marianne

2006-07-15

Prelude&Fugue are bioinformatics tools aiming at predicting the local 3D structure of a protein from its amino acid sequence in terms of seven backbone torsion angle domains, using database-derived potentials. Prelude(&Fugue) computes all lowest free energy conformations of a protein or protein region, ranked by increasing energy, and possibly satisfying some interresidue distance constraints specified by the user. (Prelude&)Fugue detects sequence regions whose predicted structure is significantly preferred relative to other conformations in the absence of tertiary interactions. These programs can be used for predicting secondary structure, tertiary structure of short peptides, flickering early folding sequences and peptides that adopt a preferred conformation in solution. They can also be used for detecting structural weaknesses, i.e. sequence regions that are not optimal with respect to the tertiary fold. http://babylone.ulb.ac.be/Prelude_and_Fugue.

Cooperative Tertiary Interaction Network Guides RNA Folding

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

Behrouzi, Reza; Roh, Joon Ho; Kilburn, Duncan

2013-04-08

Noncoding RNAs form unique 3D structures, which perform many regulatory functions. To understand how RNAs fold uniquely despite a small number of tertiary interaction motifs, we mutated the major tertiary interactions in a group I ribozyme by single-base substitutions. The resulting perturbations to the folding energy landscape were measured using SAXS, ribozyme activity, hydroxyl radical footprinting, and native PAGE. Double- and triple-mutant cycles show that most tertiary interactions have a small effect on the stability of the native state. Instead, the formation of core and peripheral structural motifs is cooperatively linked in near-native folding intermediates, and this cooperativity depends onmore » the native helix orientation. The emergence of a cooperative interaction network at an early stage of folding suppresses nonnative structures and guides the search for the native state. We suggest that cooperativity in noncoding RNAs arose from natural selection of architectures conducive to forming a unique, stable fold.« less

Tertiary Education in Britian. National Report.

ERIC Educational Resources Information Center

Eggleston, J.

Some of the major trends in British Tertiary education are reviewed. Types of schools and/or courses in British secondary education are examined in relation to student preparation for tertiary education. The present system of higher Education in Britian is described including types of institutions and academic structures, admission requirements,…

Färoe-Iceland Ridge Experiment: 1. Crustal structure of northeastern Iceland

USGS Publications Warehouse

Staples, Robert K.; White, Robert S.; Brandsdottir, Bryndis; Menke, William; Maguire, Peter K.H.; McBride, John H.

1997-01-01

Results from the Färoe-Iceland Ridge Experiment (FIRE) constrain the crustal thickness as 19 km under the Northern Volcanic Zone of Iceland and 35 km under older Tertiary areas of northeastern Iceland. The Moho is defined by strong P wave and S wave reflections. Synthetic seismogram modeling of the Moho reflection indicates mantle velocities of at least 8.0 km/s beneath the Tertiary areas of northeastern Iceland and at least 7.9 km/s beneath the neovolcanic zone. Crustal diving rays resolve the structure of the upper and lower crust. Surface P wave velocities are 1.1–4.0 km/s in Quaternary rocks and are rather higher, 4.4–4.7 km/s, in the Tertiary basalts that outcrop elsewhere. The highest crustal P wave velocities observed directly from diving rays are 7.1 km/s, from rays that turn at 24 km depth. Velocities of 7.35 km/s at the base of the crust are inferred from extrapolation of the lower crustal velocity gradient (0.024 s−1). A Poisson's ratio of approximately 0.27, equivalent to an S wave to P wave travel time ratio of 1.78, is measured throughout the crust east of the neovolcanic zone. The Poisson's ratio and the steep Moho topography (in places up to 30° from the horizontal) indicate that the entire crust outside the neovolcanic zone is cool (<800°C). Gravity data are well matched by a velocity/density conversion of our seismic crustal model and indicate a region of low mantle density beneath the neovolcanic zone, believed to be due to elevated mantle temperatures. The crustal thickness in the neovolcanic zone is consistent with geochemical estimates of the melt generation, placing constraints on the flow within the Iceland mantle plume.

The effect of increasing the coinsurance rate on outpatient utilization of healthcare services in South Korea.

PubMed

Lee, Hyo Jung; Jang, Sung-In; Park, Eun-Cheol

2017-02-20

The Korean healthcare system is composed of costly and inefficient structures that fail to adequately divide the functions and roles of medical care organizations. To resolve this matter, the government reformed the cost-sharing policy in November of 2011 for the management of outpatients visiting general or tertiary hospitals with comparatively mild diseases. The purpose of the present study was to examine the impact of increasing the coinsurance rate of prescription drug costs for 52 mild diseases at general or tertiary hospitals on outpatient healthcare service utilization. The present study used health insurance claim data collected from 2010 to 2013. The study population consisted of 505,691 outpatients and was defined as those aged 20-64 years who had visited medical care organizations for the treatment of 52 diseases both before and after the program began. To examine the effect of the cost-sharing policy on outpatient healthcare service utilization (percentage of general or tertiary hospital utilization, number of outpatient visits, and outpatient medical costs), a segmented regression analysis was performed. After the policy to increase the coinsurance rate on prescription drug costs was implemented, the number of outpatient visits at general or tertiary hospitals decreased (β = -0.0114, p < 0.0001); however, the number increased at hospitals and clinics (β = 0.0580, p < 0.0001). Eventually, the number of outpatient visits to hospitals and clinics began to decrease after policy initiation (β = -0.0018, p < 0.0001). Outpatient medical costs decreased for both medical care organizations (general or tertiary hospitals: β = -2913.4, P < 0.0001; hospitals or clinics: β = -591.35, p < 0.0001), and this decreasing trend continued with time. It is not clear that decreased utilization of general or tertiary hospitals has transferred to that of clinics or hospitals due to the increased cost-sharing policy of prescription drug costs. This result indicates the cost-sharing policy, intended to change patient behaviors for healthcare service utilization, has had limited effects on rebuilding the healthcare system and the function of medical care organizations.

Application of Landsat imagery to problems of petroleum exploration in Qaidam Basin, China

USGS Publications Warehouse

Bailey, G.B.; Anderson, P.D.

1982-01-01

Tertiary and Quaternary nonmarine, petroleum-bearing sedimentary rocks have been extensively deformed by compressive forces. These forces created many folds which are current targets of Chinese exploration programs. Image-derived interpretations of folds, strike-slip faults, thrust faults, normal or reverse faults, and fractures compared very favorably, in terms of locations and numbers mapped, with Chinese data compiled from years of extensive field mapping. Many potential hydrocarbon trapping structures were precisely located. Orientations of major structural trends defined from Landsat imagery correlate well with those predicted for the area based on global tectonic theory. These correlations suggest that similar orientations exist in the eastern half of the basin where folded rocks are mostly obscured by unconsolidated surface sediments and where limited exploration has occurred.--Modified journal abstract.

Unconstrained Structure Formation in Coarse-Grained Protein Simulations

NASA Astrophysics Data System (ADS)

Bereau, Tristan

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

Predicting RNA 3D structure using a coarse-grain helix-centered model

PubMed Central

Kerpedjiev, Peter; Höner zu Siederdissen, Christian; Hofacker, Ivo L.

2015-01-01

A 3D model of RNA structure can provide information about its function and regulation that is not possible with just the sequence or secondary structure. Current models suffer from low accuracy and long running times and either neglect or presume knowledge of the long-range interactions which stabilize the tertiary structure. Our coarse-grained, helix-based, tertiary structure model operates with only a few degrees of freedom compared with all-atom models while preserving the ability to sample tertiary structures given a secondary structure. It strikes a balance between the precision of an all-atom tertiary structure model and the simplicity and effectiveness of a secondary structure representation. It provides a simplified tool for exploring global arrangements of helices and loops within RNA structures. We provide an example of a novel energy function relying only on the positions of stems and loops. We show that coupling our model to this energy function produces predictions as good as or better than the current state of the art tools. We propose that given the wide range of conformational space that needs to be explored, a coarse-grain approach can explore more conformations in less iterations than an all-atom model coupled to a fine-grain energy function. Finally, we emphasize the overarching theme of providing an ensemble of predicted structures, something which our tool excels at, rather than providing a handful of the lowest energy structures. PMID:25904133

Toward the fourth dimension of membrane protein structure: insight into dynamics from spin-labeling EPR spectroscopy.

PubMed

McHaourab, Hassane S; Steed, P Ryan; Kazmier, Kelli

2011-11-09

Trapping membrane proteins in the confines of a crystal lattice obscures dynamic modes essential for interconversion between multiple conformations in the functional cycle. Moreover, lattice forces could conspire with detergent solubilization to stabilize a minor conformer in an ensemble thus confounding mechanistic interpretation. Spin labeling in conjunction with electron paramagnetic resonance (EPR) spectroscopy offers an exquisite window into membrane protein dynamics in the native-like environment of a lipid bilayer. Systematic application of spin labeling and EPR identifies sequence-specific secondary structures, defines their topology and their packing in the tertiary fold. Long range distance measurements (60 Å-80 Å) between pairs of spin labels enable quantitative analysis of equilibrium dynamics and triggered conformational changes. This review highlights the contribution of spin labeling to bridging structure and mechanism. Efforts to develop methods for determining structures from EPR restraints and to increase sensitivity and throughput promise to expand spin labeling applications in membrane protein structural biology. Copyright © 2011 Elsevier Ltd. All rights reserved.

Mapping the Typology of Transition Systems in a Liberal Market Economy: The Case of Canada

ERIC Educational Resources Information Center

Arnold, Christine Helen; Wheelahan, Leesa; Moodie, Gavin; Beaulieu, Jacqueline; Taylor-Cline, Jean-Claude

2018-01-01

This research explores links between tertiary education institutions and between tertiary education and the labour market as determinants of provincial and national transition patterns in Canada. The study consists of a provincial analysis that maps the typology of transition systems across Canada's devolved federated tertiary education structure.…

The Missing Link in Australian Tertiary Education: Short-Cycle Higher Education

ERIC Educational Resources Information Center

Moodie, Gavin

2003-01-01

The blurring of the boundary between Australian vocational education and training and higher education is leading to a reconsideration of the current structure of Australian tertiary education. This paper starts with the main overlap of the Australian tertiary education sectors, diplomas and advanced diplomas. The ambiguous treatment of these…

Induced helical backbone conformations of self-organizable dendronized polymers.

PubMed

Rudick, Jonathan G; Percec, Virgil

2008-12-01

Control of function through the primary structure of a molecule presents a significant challenge with valuable rewards for nanoscience. Dendritic building blocks encoded with information that defines their three-dimensional shape (e.g., flat-tapered or conical) and how they associate with each other are referred to as self-assembling dendrons. Self-organizable dendronized polymers possess a flat-tapered or conical self-assembling dendritic side chain on each repeat unit of a linear polymer backbone. When appended to a covalent polymer, the self-assembling dendrons direct a folding process (i.e., intramolecular self-assembly). Alternatively, intermolecular self-assembly of dendrons mediated by noncovalent interactions between apex groups can generate a supramolecular polymer backbone. Self-organization, as we refer to it, is the spontaneous formation of periodic and quasiperiodic arrays from supramolecular elements. Covalent and supramolecular polymers jacketed with self-assembling dendrons self-organize. The arrays are most often comprised of cylindrical or spherical objects. The shape of the object is determined by the primary structure of the dendronized polymer: the structure of the self-assembling dendron and the length of the polymer backbone. It is therefore possible to predictably generate building blocks for single-molecule nanotechnologies or arrays of supramolecules for bottom-up self-assembly. We exploit the self-organization of polymers jacketed with self-assembling dendrons to elucidate how primary structure determines the adopted conformation and fold (i.e., secondary and tertiary structure), how the supramolecules associate (i.e., quaternary structure), and their resulting functions. A combination of experimental techniques is employed to interrogate the primary, secondary, tertiary, and quaternary structure of the self-organizable dendronized polymers. We refer to the process by which we interpolate between the various levels of structural information to rationalize function as retrostructural analysis. Retrostructural analysis validates our hypothesis that the self-assembling dendrons induce a helical backbone conformation in cylindrical self-organizable dendronized polymers. This helical conformation mediates unprecedented functions. Self-organizable dendronized polymers have emerged as powerful building blocks for nanoscience by virtue of their dimensions and ability to self-organize. Discrete cylindrical and spherical structures with well-defined dimensions can be visualized and manipulated individually. More importantly, they provide a robust framework for elucidating functions available only at the nanoscale. This Account will highlight structures and functions generated from self-organizable dendronized polymers that enable integration of the nanoworld with its macroscopic universe. Emphasis is placed on those structures and functions derived from the induced helical backbone conformation of cylindrical self-organizable dendronized polymers.

Style of Cenozoic extensional deformation in the central Beaverhead Mountains, Idaho-Montana

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

Kellogg, K.S.

1993-04-01

Cenozoic extension in the upper Medicine Lodge Creek area in the Beaverhead Mountains was accommodated along numerous low- to high-angle, west-facing normal faults. These faults have repeated moderately east-dipping (by 20--40[degree]) Tertiary rocks that are as old as the Eocene Medicine Lodge Volcanics and that include conformably overlying Miocene and Oligocene conglomerate, tuffaceous sandstone, siltstone, and limestone; a reasonable restoration of Tertiary faulting suggests that the region has extended about 20 percent. At least one normal fault soles into the Late Cretaceous Cabin thrust, one of at least four major Cordilleran thrusts in the Beaverhead Mountains and the Tendoy Mountainsmore » immediately to the east. The Cabin thrust places enigmatic quartzite (age is between Middle Proterozoic and Lower Cambrian) and Archean gneiss above Mississippian to Ordovician rocks. The formation of the north-northwest-trending upper Medicine Lodge Valley was controlled mostly by low-angle normal faults along its east side, where Eocene volcanics and overlying sedimentary rocks dip about 25[degree] eastward against Archean rocks. Faceted spurs are prominent but no scarps are visible, suggesting that last movement is pre-Holocene. Other large-displacement normal faults at higher elevations show relatively little topographic expression. The Late Proterozoic or Cambrian Beaverhead impact structure, defined by wide-spread shatter-coning, pseudotachylite formation, and localized brecciation, make interpretation of some extensive breccia zones in Archean rocks along the east side of Medicine Lodge Valley problematic. The proximity of the breccias to Tertiary normal faults makes a Tertiary age attractive, yet the breccias are older than pseudotachylite interpreted to have been produced by the impact.« less

Analysis of RNA structure using small-angle X-ray scattering

PubMed Central

Cantara, William A.; Olson, Erik D.; Musier-Forsyth, Karin

2016-01-01

In addition to their role in correctly attaching specific amino acids to cognate tRNAs, aminoacyl-tRNA synthetases (aaRS) have been found to possess many alternative functions and often bind to and act on other nucleic acids. In contrast to the well-defined 3D structure of tRNA, the structures of many of the other RNAs recognized by aaRSs have not been solved. Despite advances in the use of X-ray crystallography (XRC), nuclear magnetic resonance (NMR) spectroscopy and cryo-electron microscopy (cryo-EM) for structural characterization of biomolecules, significant challenges to solving RNA structures still exist. Recently, small-angle X-ray scattering (SAXS) has been increasingly employed to characterize the 3D structures of RNAs and RNA-protein complexes. SAXS is capable of providing low-resolution tertiary structure information under physiological conditions and with less intensive sample preparation and data analysis requirements than XRC, NMR and cryo-EM. In this article, we describe best practices involved in the process of RNA and RNA-protein sample preparation, SAXS data collection, data analysis, and structural model building. PMID:27777026

Geologic and biostratigraphic framework of the non-marine Cretaceous-Tertiary boundary interval in western North America

USGS Publications Warehouse

Nichols, D.J.

1990-01-01

Palynologically defined Cretaceous-Tertiary boundary sites in nonmarine rocks in western North America exhibit similar characteristics. All are marked by abrupt disappearance of the regional uppermost Cretaceous palynoflora at the level of an iridium anomaly; most also yeild shock-metamorphosed minerals. All are in coal-bearing, fluvial or paludal depositional settings, although the boundary horizon may be below, within, above, or at some stratigraphic distance from coal seams. At many sites the lowermost Tertiary beds contain assemblages overwhelmed by fern spores that, together with extinctions of some groups of angiosperms, are taken as evidence of regional devastation of terrestrial plant communities and subsequent recolonization by pioneer species. ?? 1990.

Picosecond Phase Grating Spectroscopy of Hemoglobin and Myoglobin: Vibrational Relaxation and Global Protein Motions.

NASA Astrophysics Data System (ADS)

Genberg, Laura Lynn

The vibrational energy relaxation pathways from optically excited met heme proteins have been studied using the technique of picosecond phase grating spectroscopy. Vibrational energy transfer from the porphyrin ring to the protein backbone leads to extensive delocalization of the energy in the protein matrix which is efficiently transferred to the water interface in less than 20 ps. A slower relaxation process on the nanosecond time scale is also observed. The slow relaxation component is attributed to slow conformational relaxation processes of high potential energy states of the heme proteins. These states are accessed during the high internal energy conditions of the optically excited molecules. In addition, a detailed theoretical analysis of this form of spectroscopy is presented that explains the effects of delayed thermal energy deposition on grating dynamics. The effects of optical pulse shape and duration are also treated. The observable in this technique is not an electronic polarization, but is derived from a response of the material fields to changes in the lattice temperature. Phase grating spectroscopy is also used to observe picosecond tertiary structural changes in both myoglobin and hemoglobin following CO photodissociation. The original interest in this experiment was to ascertain whether local minima are accessed during the highly exothermic conditions following photodissociation, as was observed in the met heme studies. Photodissociation of CO induces a well defined ligated to deoxy structure transition that is important to the functionality of these proteins. Using grating spectroscopy, protein driven density waves are observed on a picosecond time scale. These waves are launched by the tertiary structural changes that occur in both hemoglobin and myoglobin. The exact shape and amplitude of these waves reveal the time scale for the motion as well as the energetics for these protein motions. This result demonstrates that tertiary structure changes are global in nature and occur on an extremely fast time scale. This provides new insight into the biomechanics of conformational changes in proteins and lends support to theoretical models invoking stored strain energy as the driving force for large amplitude correlated motions.

Interpretation of Gravimetric and Aeromagnetic Data of the Tecoripa Chart in Southeast Sonora, Mexico.

NASA Astrophysics Data System (ADS)

Martínez-Retama, S.; Montaño-Del Cid, M. A.

2015-12-01

The Tecoripa chart H12-D64 is located southeast of the state of Sonora, México, south of Arizona. The geology is represented by sedimentary rocks of the Ordovician and Triassic, volcanic rocks of the Upper Cretaceous and Tertiary, intrusive rocks from the Upper Cretaceous- Tertiary and sedimentary rocks of the Cenozoic. In this paper a gravimetric study was conducted to determine the configuration and depth of the basement and to develop a structural model of the subsurface. For this purpose a consistent gravimetric survey in 3 profiles was conducted. To complement this study, gravimetric data obtained by INEGI (96 gravimetric stations spaced every 4000 m) that correspond to a regional survey was also used. The two sets of data were corrected and processed with the WinGLink software. The profiles were then modeled using the Talwani method. 4 Profiles corresponding to the gravimetric survey and 5 data profiles from INEGI were modeled. Aeromagnetic data from the total field of Tecoripa chart were also processed. The digital information was integrated and processed by generating a data grid. Processes applied to data consisted of reduction to the pole, regional-residual separation and upward continuations. In general, the obtained structural models show intrusive bodies associated with well-defined high gravimetric and magnetic and low gravimetric and magnetic are associated with basins and sedimentary rocks. The obtained geological models show the basement represented by volcanic rocks of the Tarahumara Formation from the Upper Cretaceous which are in contact with sedimentary rocks from the Barranca Group from Upper Cretaceous and limestones from the Middle Ordovician. Both volcanic and sedimentary rocks are intruded by granodiorite- granite with ages of the Tertiary-Oligocene. Based on the superficial geology as well as in the configuration of the basement and the obtained structural model the existence of faults with NW-SE orientation that originate Horst and Graben type structures can be inferred. The basins have depths of 2,000 to 4,000m with sedimentary fillings from the Báucarit Formation and Quaternary sediments.

Seismic-Reflection Technology Defines Potential Vertical Bypass in Hydrogeologic Confinement within Tertiary Carbonates of the Southeastern Florida Platform

NASA Astrophysics Data System (ADS)

Cunningham, K. J.; Walker, C.; Westcott, R. L.

2011-12-01

Continuous improvements in shallow-focused, high-resolution, marine seismic-reflection technology has provided the opportunity to evaluate geologic structures that breach confining units of the Floridan aquifer system within the southeastern Florida Platform. The Floridan aquifer system is comprised mostly of Tertiary platform carbonates. In southeastern Florida, hydrogeologic confinement is important to sustainable use of the Floridan aquifer system, where the saline lower part is used for injection of wastewater and the brackish upper part is an alternative source of drinking water. Between 2007 and 2011, approximately 275 km of 24- and 48-channel seismic-reflection profiles were acquired in canals of peninsular southeastern Florida, Biscayne Bay, present-day Florida shelf margin, and the deeply submerged Miami Terrace. Vertical to steeply dipping offsets in seismic reflections indicate faults, which range from Eocene to possible early Pliocene age. Most faults are associated with karst collapse structures; however, a few tectonic faults of early Miocene to early Pliocene age are present. The faults may serve as a pathway for vertical groundwater flow across relatively low-permeability carbonate strata that separate zones of regionally extensive high-permeability in the Floridan aquifer system. The faults may collectively produce a regional confinement bypass system. In early 2011, twenty seismic-reflection profiles were acquired near the Key Biscayne submarine sinkhole located on the seafloor of the Miami Terrace. Here the water depth is about 365 m. A steeply dipping (eastward) zone of mostly deteriorated quality of seismic-reflection data underlies the sinkhole. Correlation of coherent seismic reflections within and adjacent to the disturbed zone indicates a series of faults occur within the zone. It is hypothesized that upward movement of groundwater within the zone contributed to development of a hypogenic karst system and the resultant overlying sinkhole. Study of this modern seafloor sinkhole may provide clues to the genesis of the more deeply buried Tertiary karst collapse structures. Three-dimensional geomodeling of the seismic-reflection data from the Key Biscayne sinkhole further aids visualization of the seismic stratigraphy and structural system that underlies the sinkhole.

Deep resistivity structure of Yucca Flat, Nevada Test Site, Nevada

USGS Publications Warehouse

Asch, Theodore H.; Rodriguez, Brian D.; Sampson, Jay A.; Wallin, Erin L.; Williams, Jackie M.

2006-01-01

The Department of Energy (DOE) and the National Nuclear Security Administration (NNSA) at their Nevada Site Office are addressing groundwater contamination resulting from historical underground nuclear testing through the Environmental Management program and, in particular, the Underground Test Area project. One issue of concern is the nature of the somewhat poorly constrained pre Tertiary geology and its effects on ground-water flow in the area adjacent to a nuclear test. Ground water modelers would like to know more about the hydrostratigraphy and geologic structure to support a hydrostratigraphic framework model that is under development for the Yucca Flat Corrective Action Unit (CAU). During 2003, the U.S. Geological Survey, supported by the DOE and NNSA-NSO, collected and processed data from 51 magnetotelluric (MT) and audio-magnetotelluric (AMT) stations at the Nevada Test Site in and near Yucca Flat to assist in characterizing the pre-Tertiary geology in that area. The primary purpose was to refine the character, thickness, and lateral extent of pre Tertiary confining units. In particular, a major goal has been to define the upper clastic confining unit (late Devonian - Mississippian-age siliciclastic rocks assigned to the Eleana Formation and Chainman Shale) in the Yucca Flat area. The MT and AMT data have been released in separate USGS Open File Reports. The Nevada Test Site magnetotelluric data interpretation presented in this report includes the results of detailed two-dimensional (2 D) resistivity modeling for each profile (including alternative interpretations) and gross inferences on the three dimensional (3 D) character of the geology beneath each station. The character, thickness, and lateral extent of the Chainman Shale and Eleana Formation that comprise the Upper Clastic Confining Unit are generally well determined in the upper 5 km. Inferences can be made regarding the presence of the Lower Clastic Confining Unit at depths below 5 km. Large fault structures such as the CP Thrust fault, the Carpetbag fault, and the Yucca fault that cross Yucca Flat are also discernable as are other smaller faults. The subsurface electrical resistivity distribution and inferred geologic structures determined by this investigation should help constrain the hydrostratigraphic framework model that is under development.

Conformational analysis of processivity clamps in solution demonstrates that tertiary structure does not correlate with protein dynamics.

PubMed

Fang, Jing; Nevin, Philip; Kairys, Visvaldas; Venclovas, Česlovas; Engen, John R; Beuning, Penny J

2014-04-08

The relationship between protein sequence, structure, and dynamics has been elusive. Here, we report a comprehensive analysis using an in-solution experimental approach to study how the conservation of tertiary structure correlates with protein dynamics. Hydrogen exchange measurements of eight processivity clamp proteins from different species revealed that, despite highly similar three-dimensional structures, clamp proteins display a wide range of dynamic behavior. Differences were apparent both for structurally similar domains within proteins and for corresponding domains of different proteins. Several of the clamps contained regions that underwent local unfolding with different half-lives. We also observed a conserved pattern of alternating dynamics of the α helices lining the inner pore of the clamps as well as a correlation between dynamics and the number of salt bridges in these α helices. Our observations reveal that tertiary structure and dynamics are not directly correlated and that primary structure plays an important role in dynamics. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Unique Significance and Origin of the Cretaceous-Tertiary Boundary: Historical Context and Burdens of Proof

NASA Technical Reports Server (NTRS)

Ryder, Graham

1996-01-01

The abruptness and intensity of the Cretaceous-Tertiary boundary have been deemphasized by some authors over recent years, mainly by those skeptical of an impact origin for the boundary. However, it was recognized at the birth of stratigraphy as both abrupt and of major importance. It was used to define the change from the Mesozoic to the Cenozoic; the boundary has become continually more precisely defined and its global sequences more correlatable. It is now unique in being an event boundary marked by an iridium-bearing layer of global extent, rather than an arbitrary boundary in a sequence of little change. The Permian-Triassic boundary, in contrast, is arbitrary and the transition is not yet proven to be abrupt, the extinctions that define it perhaps having taken place in pulses over several millions of years. Some of those who have denied the importance (and in some cases even the existence) of an impact in the Cretaceous-Tertiary extinctions have placed burdens of proof on the impact hypothesis that they do not place on strictly terrestrial mechanisms. Terrestrial mechanisms have always been unsatisfactory (or at least unconvincing for global, massive, multienvironment faunal change) and are now even more so. Some authors have required of the impact hypothesis attributes that are not inherent in it, including particular patterns of extinction selectivity and timing.

Tertiary network in mammalian mitochondrial tRNAAsp revealed by solution probing and phylogeny

PubMed Central

Messmer, Marie; Pütz, Joern; Suzuki, Takeo; Suzuki, Tsutomu; Sauter, Claude; Sissler, Marie; Catherine, Florentz

2009-01-01

Primary and secondary structures of mammalian mitochondrial (mt) tRNAs are divergent from canonical tRNA structures due to highly skewed nucleotide content and large size variability of D- and T-loops. The nonconservation of nucleotides involved in the expected network of tertiary interactions calls into question the rules governing a functional L-shaped three-dimensional (3D) structure. Here, we report the solution structure of human mt-tRNAAsp in its native post-transcriptionally modified form and as an in vitro transcript. Probing performed with nuclease S1, ribonuclease V1, dimethylsulfate, diethylpyrocarbonate and lead, revealed several secondary structures for the in vitro transcribed mt-tRNAAsp including predominantly the cloverleaf. On the contrary, the native tRNAAsp folds into a single cloverleaf structure, highlighting the contribution of the four newly identified post-transcriptional modifications to correct folding. Reactivities of nucleotides and phosphodiester bonds in the native tRNA favor existence of a full set of six classical tertiary interactions between the D-domain and the variable region, forming the core of the 3D structure. Reactivities of D- and T-loop nucleotides support an absence of interactions between these domains. According to multiple sequence alignments and search for conservation of Leontis–Westhof interactions, the tertiary network core building rules apply to all tRNAAsp from mammalian mitochondria. PMID:19767615

Automated 3D structure composition for large RNAs

PubMed Central

Popenda, Mariusz; Szachniuk, Marta; Antczak, Maciej; Purzycka, Katarzyna J.; Lukasiak, Piotr; Bartol, Natalia; Blazewicz, Jacek; Adamiak, Ryszard W.

2012-01-01

Understanding the numerous functions that RNAs play in living cells depends critically on knowledge of their three-dimensional structure. Due to the difficulties in experimentally assessing structures of large RNAs, there is currently great demand for new high-resolution structure prediction methods. We present the novel method for the fully automated prediction of RNA 3D structures from a user-defined secondary structure. The concept is founded on the machine translation system. The translation engine operates on the RNA FRABASE database tailored to the dictionary relating the RNA secondary structure and tertiary structure elements. The translation algorithm is very fast. Initial 3D structure is composed in a range of seconds on a single processor. The method assures the prediction of large RNA 3D structures of high quality. Our approach needs neither structural templates nor RNA sequence alignment, required for comparative methods. This enables the building of unresolved yet native and artificial RNA structures. The method is implemented in a publicly available, user-friendly server RNAComposer. It works in an interactive mode and a batch mode. The batch mode is designed for large-scale modelling and accepts atomic distance restraints. Presently, the server is set to build RNA structures of up to 500 residues. PMID:22539264

Insights upon upper crustal arhitecture of a subduction zone and its surroundings - Vrancea Zone and Focsani Basin - substantiated by geophysical studies

NASA Astrophysics Data System (ADS)

Bocin, A.; Stephenson, R.; Mocanu, V.

2007-12-01

The DACIA PLAN (Danube and Carpathian Integrated Action on Processes in the Lithosphere and Neotectonics) deep seismic reflection survey was performed in August-September 2001, with the proposed objective of obtaining new information on the deep structure of the external Carpathians nappes and the architecture of Tertiary/Quaternary basin developed within and adjacent to the Vrancea zone, including the rapidly subsiding Focsani Basin. The DACIA-PLAN profile is about 140 km long, having a roughly NW-SE direction, from near the southeast Transylvanian Basin, across the mountainous southeastern Carpathians and their foreland to near the Danube River. A high resolution 2.5D velocity model of the upper crust along the seismic profile has been determined from a tomographic inversion and a 2D ray tracing forward modelling of the DACIA PLAN first arrival data. Peculiar shallow high velocities indicate that pre-Tertiary basement in the Vrancea Zone (characterised by velocities greater than 5.6 km/s) is involved in Carpathian thrusting while rapid alternance, vertically or horizontally, of velocity together with narrowingly contemporary crustal events suggests uplifting. Further to the east, at the foreland basin-thrust belt transition zone (well defined within velocity values), the velocity model suggests a nose of the Miocene Subcarpathians nappe being underlain by Focsani Basin units. A Miocene and younger Focsani Basin sedimentary succession of ~10 km thickness is ascertained by a gradual increase of velocities and strongly defined velocity boundaries.

Structural mechanism of laforin function in glycogen dephosphorylation and lafora disease.

PubMed

Raththagala, Madushi; Brewer, M Kathryn; Parker, Matthew W; Sherwood, Amanda R; Wong, Brian K; Hsu, Simon; Bridges, Travis M; Paasch, Bradley C; Hellman, Lance M; Husodo, Satrio; Meekins, David A; Taylor, Adam O; Turner, Benjamin D; Auger, Kyle D; Dukhande, Vikas V; Chakravarthy, Srinivas; Sanz, Pascual; Woods, Virgil L; Li, Sheng; Vander Kooi, Craig W; Gentry, Matthew S

2015-01-22

Glycogen is the major mammalian glucose storage cache and is critical for energy homeostasis. Glycogen synthesis in neurons must be tightly controlled due to neuronal sensitivity to perturbations in glycogen metabolism. Lafora disease (LD) is a fatal, congenital, neurodegenerative epilepsy. Mutations in the gene encoding the glycogen phosphatase laforin result in hyperphosphorylated glycogen that forms water-insoluble inclusions called Lafora bodies (LBs). LBs induce neuronal apoptosis and are the causative agent of LD. The mechanism of glycogen dephosphorylation by laforin and dysfunction in LD is unknown. We report the crystal structure of laforin bound to phosphoglucan product, revealing its unique integrated tertiary and quaternary structure. Structure-guided mutagenesis combined with biophysical and biochemical analyses reveal the basis for normal function of laforin in glycogen metabolism. Analyses of LD patient mutations define the mechanism by which subsets of mutations disrupt laforin function. These data provide fundamental insights connecting glycogen metabolism to neurodegenerative disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Structural Feasibility Analysis of a Robotically Assembled Very Large Aperture Optical Space Telescope

NASA Technical Reports Server (NTRS)

Wilkie, William Keats; Williams, R. Brett; Agnes, Gregory S.; Wilcox, Brian H.

2007-01-01

This paper presents a feasibility study of robotically constructing a very large aperture optical space telescope on-orbit. Since the largest engineering challenges are likely to reside in the design and assembly of the 150-m diameter primary reflector, this preliminary study focuses on this component. The same technology developed for construction of the primary would then be readily used for the smaller optical structures (secondary, tertiary, etc.). A reasonable set of ground and on-orbit loading scenarios are compiled from the literature and used to define the structural performance requirements and size the primary reflector. A surface precision analysis shows that active adjustment of the primary structure is required in order to meet stringent optical surface requirements. Two potential actuation strategies are discussed along with potential actuation devices at the current state of the art. The finding of this research effort indicate that successful technology development combined with further analysis will likely enable such a telescope to be built in the future.

Why Do Tertiary Education Graduates Regret Their Study Program? A Comparison between Spain and the Netherlands

ERIC Educational Resources Information Center

Kucel, Aleksander; Vilalta-Bufi, Montserrat

2013-01-01

In this paper we investigate the determinants of regret of study program for tertiary education graduates in Spain and the Netherlands. These two countries differ in their educational system in terms of the tracking structure in their secondary education and the strength of their education-labor market linkages in tertiary education. Therefore, by…

RNA Tertiary Interactions in a Riboswitch Stabilize the Structure of a Kink Turn

PubMed Central

Schroeder, Kersten T.; Daldrop, Peter; Lilley, David M.J.

2011-01-01

Summary The kink turn is a widespread RNA motif that introduces an acute kink into the axis of duplex RNA, typically comprising a bulge followed by a G⋅A and A⋅G pairs. The kinked conformation is stabilized by metal ions, or the binding of proteins including L7Ae. We now demonstrate a third mechanism for the stabilization of k-turn structure, involving tertiary interactions within a larger RNA structure. The SAM-I riboswitch contains an essential standard k-turn sequence that kinks a helix so that its terminal loop can make a long-range interaction. We find that some sequence variations in the k-turn within the riboswitch do not prevent SAM binding, despite preventing the folding of the k-turn in isolation. Furthermore, two crystal structures show that the sequence-variant k-turns are conventionally folded within the riboswitch. This study shows that the folded structure of the k-turn can be stabilized by tertiary interactions within a larger RNA structure. PMID:21893284

Perinatal market penetration rate. A tool to evaluate regional perinatal programs.

PubMed

Powers, W F; McGill, L

1987-01-01

Very small babies born in tertiary centers fare better than outborn babies referred for tertiary care after birth. Viewing the 1001-1500 gm regional cohort of fetuses as a potential "market" for center delivery, and measuring a center's penetration into this market, quantitates how well a center draws to itself these small, high-risk fetuses for delivery. An Illinois center's annual penetration rate into its regional market for the years 1973-1983 is presented and significant increases are found. The penetration rates of nine Illinois perinatal centers are calculated and wide discrepancies are found. Defining a high-risk regional cohort as a market stresses a perinatal center's obligation to its region. The penetration rate into a defined market measures how well a center fulfills this obligation.

Tandem Carbocupration/Oxygenation of Terminal Alkynes

PubMed Central

Zhang, Donghui; Ready, Joseph M.

2008-01-01

A direct and general synthesis of α-branched aldehydes and their enol derivatives is described. Carbocupration of terminal alkynes and subsequent oxygenation with lithium tert-butyl peroxide generates a metallo-enolate. Trapping with various electrophiles provides α-branched aldehydes or stereo-defined trisubstituted enol esters or silyl ethers. The tandem carbocupration/oxygenation tolerates alkyl and silyl ethers, esters and tertiary amines. The reaction is effective with organocopper complexes derived from primary, secondary and tertiary Grignard reagents and from n-butyllithium. PMID:16321021

New Mexico structural zone - An analogue of the Colorado mineral belt

USGS Publications Warehouse

Sims, P.K.; Stein, H.J.; Finn, C.A.

2002-01-01

Updated aeromagnetic maps of New Mexico together with current knowledge of the basement geology in the northern part of the state (Sangre de Cristo and Sandia-Manzano Mountains)-where basement rocks were exposed in Precambrian-cored uplifts-indicate that the northeast-trending Proterozoic shear zones that controlled localization of ore deposits in the Colorado mineral belt extend laterally into New Mexico. The shear zones in New Mexico coincide spatially with known epigenetic precious- and base-metal ore deposits; thus, the mineralized belts in the two states share a common inherited basement tectonic setting. Reactivation of the basement structures in Late Cretaceous-Eocene and Mid-Tertiary times provided zones of weakness for emplacement of magmas and conduits for ore-forming solutions. Ore deposits in the Colorado mineral belt are of both Late Cretaceous-Eocene and Mid-Tertiary age; those in New Mexico are predominantly Mid-Tertiary in age, but include Late Cretaceous porphyry-copper deposits in southwestern New Mexico. The mineralized belt in New Mexico, named the New Mexico structural zone, is 250-km wide. The northwest boundary is the Jemez subzone (or the approximately equivalent Globe belt), and the southeastern boundary was approximately marked by the Santa Rita belt. Three groups (subzones) of mineral deposits characterize the structural zone: (1) Mid-Tertiary porphyry molybdenite and alkaline-precious-metal deposits, in the northeast segment of the Jemez zone; (2) Mid-Tertiary epithermal precious-metal deposits in the Tijeras (intermediate) zone; and (3) Late Cretaceous porphyry-copper deposits in the Santa Rita zone. The structural zone was inferred to extend from New Mexico into adjacent Arizona. The structural zone provides favorable sites for exploration, particularly those parts of the Jemez subzone covered by Neogene volcanic and sedimentary rocks. ?? 2002 Published by Elsevier Science B.V.

Immunological Characterization of Intraocular Lymphoid Follicles in a Spontaneous Recurrent Uveitis Model.

PubMed

Kleinwort, Kristina J H; Amann, Barbara; Hauck, Stefanie M; Feederle, Regina; Sekundo, Walter; Deeg, Cornelia A

2016-08-01

Recently, formation of tertiary lymphoid structures was demonstrated and further characterized in the R161H mouse model of spontaneous autoimmune uveitis. In the horse model of spontaneous recurrent uveitis, intraocular lymphoid follicle formation is highly characteristic, and found in all stages and scores of disease, but in depth analyses of immunologic features of these structures are lacking to date. Paraffin-embedded eye sections of cases with equine spontaneous recurrent uveitis (ERU) were characterized with immunohistochemistry to gain insight into the distribution, localization, and signaling of immune cells in intraocular tertiary lymphoid tissues. Ectopic lymphoid tissues were located preferentially in the iris, ciliary body, and retina at the ora serrata of horses with naturally-occurring ERU. The majority of cells in the tertiary lymphoid follicles were T cells with a scattered distribution of B cells and PNA+ cells interspersed. A fraction of T cells was additionally positive for memory cell marker CD45RO. Almost all cells coexpressed CD166, a molecule associated with activation and transmigration of T cells into inflamed tissues. Several transcription factors that govern immune cell responses were detectable in the tertiary lymphoid follicles, among them Zap70, TFIIB, GATA3, and IRF4. A high expression of the phosphorylated signal transducers and activators of transcription (STAT) proteins 1 and 5 were found at the margin of the structures. Cellular composition and structural organization of these inflammation-associated tertiary lymphoid tissue structures and the expression of markers of matured T and B cells point to highly organized adaptive immune responses in these follicles in spontaneous recurrent uveitis.

Structure of the Tucson Basin, Arizona from gravity and aeromagnetic data

USGS Publications Warehouse

Rystrom, Victoria Louise

2003-01-01

Interpretation of gravity and high-resolution aeromagnetic data reveal the three-dimensional geometry of the Tuscson Basin, Arizona and the lithology of its basement. Limited drill hole and seismic data indicate that the maximum depth to the crystalline basement is approximately 3600 meters and that the sedimentary sequences in the upper ~2000 m of the basin were deposited during the most recent extensional episode that commenced about 13 Ma. The negative density contrasts between these upper Neogene and Quaternary sedimentary sequences and the adjacent country rock produce a Bouguer residual gravity low, whose steep gradients clearly define the lateral extent of the upper ~2000m of the basin. The aeromagnetic maps show large positive anomalies associated with deeply buried, late Cretaceous-early Tertiary and mid-Tertiary igneous rocks at and below the surface of the basin. These magnetic anomalies provide insight into the older (>13 Ma) and deeper structures of the basin. Simultaneous 2.5-dimensional modeling of both gravity and magnetic anomalies constrained by geologic and seismic data delineates the thickness of the basin and the dips of the buried faults that bound the basin. This geologic-based forward modeling approach to using geophysical data is shown to result in more information about the geologic and tectonic history of the basin as well as more accurate depth to basement determinations than using generalized geophysical inversion techniques.

RNA chaperone StpA loosens interactions of the tertiary structure in the td group I intron in vivo

PubMed Central

Waldsich, Christina; Grossberger, Rupert; Schroeder, Renée

2002-01-01

Efficient splicing of the td group I intron in vivo is dependent on the ribosome. In the absence of translation, the pre-mRNA is trapped in nonnative-splicing-incompetent conformations. Alternatively, folding of the pre-mRNA can be promoted by the RNA chaperone StpA or by the group I intron-specific splicing factor Cyt-18. To understand the mechanism of action of RNA chaperones, we probed the impact of StpA on the structure of the td intron in vivo. Our data suggest that StpA loosens tertiary interactions. The most prominent structural change was the opening of the base triples, which are involved in the correct orientation of the two major intron core domains. In line with the destabilizing activity of StpA, splicing of mutant introns with a reduced structural stability is sensitive to StpA. In contrast, Cyt-18 strengthens tertiary contacts, thereby rescuing splicing of structurally compromised td mutants in vivo. Our data provide direct evidence for protein-induced conformational changes within catalytic RNA in vivo. Whereas StpA resolves tertiary contacts enabling the RNA to refold, Cyt-18 contributes to the overall compactness of the td intron in vivo. PMID:12208852

Defining English Language Proficiency for Malaysian Tertiary Education: Past, Present and Future Efforts

ERIC Educational Resources Information Center

Heng, Chan Swee

2012-01-01

Any attempt to define English language proficiency can never be divorced from the theories that describe the nature of language, language acquisition and human cognition. By virtue of such theories being socially constructed, the descriptions are necessarily value-laden. Thus, a definition of language proficiency can only, at best, be described as…

Detection of groundwater conduits in limestones with gravity surveys: data from the area of the Chicxulub Impact crater, Yucatan Peninsula, Mexico.

PubMed

Kinsland, G L; Hurtado, M; Pope, K O

2000-04-15

Small negative gravity anomalies are found in gravity data from along the northwestern shoreline of the Yucatan Peninsula. These anomalies are shown to be due to elongate, shallow anomalous porosity zones in the Tertiary carbonates. These zones are caused primarily by groundwater solution and are presently active conduits for groundwater flow. The association of these small gravity anomalies with known topographic and structural features of the area, which partially overlies the Chicxulub Impact crater, indicates their development was influenced by structures, faults and/or fractures, within the Tertiary and pre-Tertiary carbonates.

Detection of groundwater conduits in limestones with gravity surveys: data from the area of the Chicxulub Impact crater, Yucatan Peninsula, Mexico

NASA Technical Reports Server (NTRS)

Kinsland, G. L.; Hurtado, M.; Pope, K. O.; Ocampo, A. C. (Principal Investigator)

2000-01-01

Small negative gravity anomalies are found in gravity data from along the northwestern shoreline of the Yucatan Peninsula. These anomalies are shown to be due to elongate, shallow anomalous porosity zones in the Tertiary carbonates. These zones are caused primarily by groundwater solution and are presently active conduits for groundwater flow. The association of these small gravity anomalies with known topographic and structural features of the area, which partially overlies the Chicxulub Impact crater, indicates their development was influenced by structures, faults and/or fractures, within the Tertiary and pre-Tertiary carbonates.

Effects of Polymer Hydrophobicity on Protein Structure and Aggregation Kinetics in Crowded Milieu.

PubMed

Breydo, Leonid; Sales, Amanda E; Frege, Telma; Howell, Mark C; Zaslavsky, Boris Y; Uversky, Vladimir N

2015-05-19

We examined the effects of water-soluble polymers of various degrees of hydrophobicity on the folding and aggregation of proteins. The polymers we chose were polyethylene glycol (PEG) and UCON (1:1 copolymer of ethylene glycol and propylene glycol). The presence of additional methyl groups in UCON makes it more hydrophobic than PEG. Our earlier analysis revealed that similarly sized PEG and UCON produced different changes in the solvent properties of water in their solutions and induced morphologically different α-synuclein aggregates [Ferreira, L. A., et al. (2015) Role of solvent properties of aqueous media in macromolecular crowding effects. J. Biomol. Struct. Dyn., in press]. To improve our understanding of molecular mechanisms defining behavior of proteins in a crowded environment, we tested the effects of these polymers on secondary and tertiary structure and aromatic residue solvent accessibility of 10 proteins [five folded proteins, two hybrid proteins; i.e., protein containing ordered and disordered domains, and three intrinsically disordered proteins (IDPs)] and on the aggregation kinetics of insulin and α-synuclein. We found that effects of both polymers on secondary and tertiary structures of folded and hybrid proteins were rather limited with slight unfolding observed in some cases. Solvent accessibility of aromatic residues was significantly increased for the majority of the studied proteins in the presence of UCON but not PEG. PEG also accelerated the aggregation of protein into amyloid fibrils, whereas UCON promoted aggregation to amyloid oligomers instead. These results indicate that even a relatively small change in polymer structure leads to a significant change in the effect of this polymer on protein folding and aggregation. This is an indication that protein folding and especially aggregation are highly sensitive to the presence of other macromolecules, and an excluded volume effect is insufficient to describe their effect.

A deep learning framework for modeling structural features of RNA-binding protein targets

PubMed Central

Zhang, Sai; Zhou, Jingtian; Hu, Hailin; Gong, Haipeng; Chen, Ligong; Cheng, Chao; Zeng, Jianyang

2016-01-01

RNA-binding proteins (RBPs) play important roles in the post-transcriptional control of RNAs. Identifying RBP binding sites and characterizing RBP binding preferences are key steps toward understanding the basic mechanisms of the post-transcriptional gene regulation. Though numerous computational methods have been developed for modeling RBP binding preferences, discovering a complete structural representation of the RBP targets by integrating their available structural features in all three dimensions is still a challenging task. In this paper, we develop a general and flexible deep learning framework for modeling structural binding preferences and predicting binding sites of RBPs, which takes (predicted) RNA tertiary structural information into account for the first time. Our framework constructs a unified representation that characterizes the structural specificities of RBP targets in all three dimensions, which can be further used to predict novel candidate binding sites and discover potential binding motifs. Through testing on the real CLIP-seq datasets, we have demonstrated that our deep learning framework can automatically extract effective hidden structural features from the encoded raw sequence and structural profiles, and predict accurate RBP binding sites. In addition, we have conducted the first study to show that integrating the additional RNA tertiary structural features can improve the model performance in predicting RBP binding sites, especially for the polypyrimidine tract-binding protein (PTB), which also provides a new evidence to support the view that RBPs may own specific tertiary structural binding preferences. In particular, the tests on the internal ribosome entry site (IRES) segments yield satisfiable results with experimental support from the literature and further demonstrate the necessity of incorporating RNA tertiary structural information into the prediction model. The source code of our approach can be found in https://github.com/thucombio/deepnet-rbp. PMID:26467480

Structure-Function Study of Tertiary Amines as Switchable Polarity Solvents

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

Aaron D. Wilson; Frederick F. Stewart

2014-02-01

A series of tertiary amines have been screened for their function as switchable polarity solvents (SPS). The relative ratios of tertiary amine and carbonate species as well as maximum possible concentration were determined through quantitative 1H and 13C NMR spectroscopy. The viscosities of the polar SPS solutions were measured and ranged from near water in dilute systems through to gel formation at high concentrations. The van't Hoff indices for SPS solutions were measured through freezing point depression studies as a proxy for osmotic pressures. A new form of SPS with an amine : carbonate ratio significantly greater than unity hasmore » been identified. Tertiary amines that function as SPS at ambient pressures appear to be limited to molecules with fewer than 12 carbons. The N,N-dimethyl-n-alkylamine structure has been identified as important to the function of an SPS.« less

Clusters of isoleucine, leucine, and valine side chains define cores of stability in high-energy states of globular proteins: Sequence determinants of structure and stability.

PubMed

Kathuria, Sagar V; Chan, Yvonne H; Nobrega, R Paul; Özen, Ayşegül; Matthews, C Robert

2016-03-01

Measurements of protection against exchange of main chain amide hydrogens (NH) with solvent hydrogens in globular proteins have provided remarkable insights into the structures of rare high-energy states that populate their folding free-energy surfaces. Lacking, however, has been a unifying theory that rationalizes these high-energy states in terms of the structures and sequences of their resident proteins. The Branched Aliphatic Side Chain (BASiC) hypothesis has been developed to explain the observed patterns of protection in a pair of TIM barrel proteins. This hypothesis supposes that the side chains of isoleucine, leucine, and valine (ILV) residues often form large hydrophobic clusters that very effectively impede the penetration of water to their underlying hydrogen bond networks and, thereby, enhance the protection against solvent exchange. The linkage between the secondary and tertiary structures enables these ILV clusters to serve as cores of stability in high-energy partially folded states. Statistically significant correlations between the locations of large ILV clusters in native conformations and strong protection against exchange for a variety of motifs reported in the literature support the generality of the BASiC hypothesis. The results also illustrate the necessity to elaborate this simple hypothesis to account for the roles of adjacent hydrocarbon moieties in defining stability cores of partially folded states along folding reaction coordinates. © 2015 The Protein Society.

Base pair probability estimates improve the prediction accuracy of RNA non-canonical base pairs

PubMed Central

2017-01-01

Prediction of RNA tertiary structure from sequence is an important problem, but generating accurate structure models for even short sequences remains difficult. Predictions of RNA tertiary structure tend to be least accurate in loop regions, where non-canonical pairs are important for determining the details of structure. Non-canonical pairs can be predicted using a knowledge-based model of structure that scores nucleotide cyclic motifs, or NCMs. In this work, a partition function algorithm is introduced that allows the estimation of base pairing probabilities for both canonical and non-canonical interactions. Pairs that are predicted to be probable are more likely to be found in the true structure than pairs of lower probability. Pair probability estimates can be further improved by predicting the structure conserved across multiple homologous sequences using the TurboFold algorithm. These pairing probabilities, used in concert with prior knowledge of the canonical secondary structure, allow accurate inference of non-canonical pairs, an important step towards accurate prediction of the full tertiary structure. Software to predict non-canonical base pairs and pairing probabilities is now provided as part of the RNAstructure software package. PMID:29107980

Elevated lateral stress in unlithified sediment, Midcontinent, United States - geotechnical and geophysical indicators for a tectonic origin

USGS Publications Warehouse

Woolery, E.W.; Schaefer, J.A.; Wang, Z.

2003-01-01

Indirect and direct geotechnical measurements revealed the presence of high lateral earth pressure (Ko) in shallow, unlithified sediment at a site in the northernmost Mississippi embayment region of the central United States. Results from pile-load and pressuremeter tests showed maximum Ko values greater than 10; however, the complex geologic environment of the Midcontinent made defining an origin for the anomalous Ko based solely on these measurements equivocal. Although in situ sediment characteristics indicated that indirect tectonic or nontectonic geologic mechanisms that include transient overburden loads (e.g., fluvial deposition/erosion, glacial advance/retreat) and dynamic shear loads (e.g., earthquakes) were not the dominant cause, they were unable to provide indicators for a direct tectonic generation. Localized stresses induced anthropogenically by the geotechnical field tests were also considered, but ruled out as the primary origin. A high-resolution shear-wave (SH) reflection image of geologic structure in the immediate vicinity of the test site revealed compression-style neotectonism, and suggested that the elevated stress was a tectonic manifestation. Post-Paleozoic reflectors exhibit a Tertiary (?) structural inversion, as evidenced by post-Cretaceous fault displacement and pronounced positive folds in the hanging wall of the interpreted faults. The latest stratigraphic extent of the stress effects (i.e., all measurements were in the Late Cretaceous to Tertiary McNairy Formation), as well as the relationship of stress orientation with the orientation of local structure and regional stress, remain unknown. These are the subjects of ongoing studies. ?? 2003 Elsevier Science B.V. All rights reserved.

An Amino Acid Code for Irregular and Mixed Protein Packing

PubMed Central

Joo, Hyun; Chavan, Archana; Fraga, Keith; Tsai, Jerry

2015-01-01

To advance our understanding of protein tertiary structure, the development of the knob-socket model is completed in an analysis of the packing in irregular coil and turn secondary structure packing as well as between mixed secondary structure. The knob-socket model simplifies packing based on repeated patterns of 2 motifs: a 3 residue socket for packing within 2° structure and a 4 residue knob-socket for 3° packing. For coil and turn secondary structure, knob-sockets allow identification of a correlation between amino acid composition and tertiary arrangements in space. Coil contributes almost as much as α-helices to tertiary packing. Irregular secondary structure involves 3 residue cliques of consecutive contacting residues or XYZ sockets. In irregular sockets, Gly, Pro, Asp and Ser are favored, while Cys, His, Met and Trp are not. For irregular knobs, the preference order is Arg, Asp, Pro, Asn, Thr, Leu, and Gly, while Cys, His, Met and Trp are not. In mixed packing, the knob amino acid preferences are a function of the socket that they are packing into, whereas the amino acid composition of the sockets does not depend on the secondary structure of the knob. A unique motif of a coil knob with an XYZ β-sheet socket may potentially function to inhibit β-sheet extension. In addition, analysis of the preferred crossing angles for strands within a β-sheet and mixed α-helices/β-sheets identifies canonical packing patterns useful in protein design. Lastly, the knob-socket model abstracts the complexity of protein tertiary structure into an intuitive packing surface topology map. PMID:26370334

Geologic framework of the Alaska Peninsula, southwest Alaska, and the Alaska Peninsula terrane

USGS Publications Warehouse

Wilson, Frederic H.; Detterman, Robert L.; DuBois, Gregory D.

2015-01-01

The boundaries separating the Alaska Peninsula terrane from other terranes are commonly indistinct or poorly defined. A few boundaries have been defined at major faults, although the extensions of these faults are speculative through some areas. The west side of the Alaska Peninsula terrane is overlapped by Tertiary sedimentary and volcanic rocks and Quaternary deposits.

Smart Utilization of Tertiary Instructional Modes

ERIC Educational Resources Information Center

Hamilton, John; Tee, Singwhat

2010-01-01

This empirical research surveys first year tertiary business students across different campuses regarding their perceived views concerning traditional, blended and flexible instructional approaches. A structural equation modeling approach shows traditional instructional modes deliver lower levels of student-perceived learning quality, learning…

Geologic assessment of undiscovered oil and gas resources: Oligocene Frio and Anahuac Formations, United States Gulf of Mexico coastal plain and State waters

USGS Publications Warehouse

Swanson, Sharon M.; Karlsen, Alexander W.; Valentine, Brett J.

2013-01-01

The Oligocene Frio and Anahuac Formations were assessed as part of the 2007 U.S. Geological Survey (USGS) assessment of Tertiary strata of the U.S. Gulf of Mexico Basin onshore and State waters. The Frio Formation, which consists of sand-rich fluvio-deltaic systems, has been one of the largest hydrocarbon producers from the Paleogene in the Gulf of Mexico. The Anahuac Formation, an extensive transgressive marine shale overlying the Frio Formation, contains deltaic and slope sandstones in Louisiana and Texas and carbonate rocks in the eastern Gulf of Mexico. In downdip areas of the Frio and Anahuac Formations, traps associated with faulted, rollover anticlines are common. Structural traps commonly occur in combination with stratigraphic traps. Faulted salt domes in the Frio and Anahuac Formations are present in the Houston embayment of Texas and in south Louisiana. In the Frio Formation, stratigraphic traps are found in fluvial, deltaic, barrier-bar, shelf, and strandplain systems. The USGS Tertiary Assessment Team defined a single, Upper Jurassic-Cretaceous-Tertiary Composite Total Petroleum System (TPS) for the Gulf Coast basin, based on previous studies and geochemical analysis of oils in the Gulf Coast basin. The primary source rocks for oil and gas within Cenozoic petroleum systems, including Frio Formation reservoirs, in the northern, onshore Gulf Coastal region consist of coal and shale rich in organic matter within the Wilcox Group (Paleocene–Eocene), with some contributions from the Sparta Sand of the Claiborne Group (Eocene). The Jurassic Smackover Formation and Cretaceous Eagle Ford Formation also may have contributed substantial petroleum to Cenozoic reservoirs. Modeling studies of thermal maturity by the USGS Tertiary Assessment Team indicate that downdip portions of the basal Wilcox Group reached sufficient thermal maturity to generate hydrocarbons by early Eocene; this early maturation is the result of rapid sediment accumulation in the early Tertiary, combined with the reaction kinetic parameters used in the models. A number of studies indicate that the migration of oil and gas in the Cenozoic Gulf of Mexico basin is primarily vertical, occurring along abundant growth faults associated with sediment deposition or along faults associated with salt domes. The USGS Tertiary assessment team developed a geologic model based on recurring regional-scale structural and depositional features in Paleogene strata to define assessment units (AUs). Three general areas, as described in the model, are found in each of the Paleogene stratigraphic intervals assessed: “Stable Shelf,” “Expanded Fault,” and “Slope and Basin Floor” zones. On the basis of this model, three AUs for the Frio Formation were defined: (1) the Frio Stable Shelf Oil and Gas AU, containing reservoirs with a mean depth of about 4,800 feet in normally pressured intervals; (2) the Frio Expanded Fault Zone Oil and Gas AU, containing reservoirs with a mean depth of about 9,000 feet in primarily overpressured intervals; and (3) the Frio Slope and Basin Floor Gas AU, which currently has no production but has potential for deep gas resources (>15,000 feet). AUs also were defined for the Hackberry trend, which consists of a slope facies stratigraphically in the middle part of the Frio Formation, and the Anahuac Formation. The Frio Basin Margin AU, an assessment unit extending to the outcrop of the Frio (or basal Miocene), was not quantitatively assessed because of its low potential for production. Two proprietary, commercially available databases containing field and well production information were used in the assessment. Estimates of undiscovered resources for the five AUs were based on a total of 1,734 reservoirs and 586,500 wells producing from the Frio and Anahuac Formations. Estimated total mean values of technically recoverable, undiscovered resources are 172 million barrels of oil (MMBO), 9.4 trillion cubic feet of natural gas (TCFG), and 542 million barrels of natural gas liquids for all of the Frio and Anahuac AUs. Of the five units assessed, the Frio Slope and Basin Floor Gas AU has the greatest potential for undiscovered gas resources, having an estimated mean of 5.6 TCFG. The Hackberry Oil and Gas AU shows the second highest potential for gas of the five units assessed, having an estimated mean of 1.8 TCFG. The largest undiscovered, conventional crude oil resource was estimated for the Frio Slope and Basin Floor Gas AU; the estimated mean for oil in this AU is 110 MMBO.

The algebra of healthcare reform: hospital-physician economic alignment.

PubMed

Goodroe, J H; Murphy, D A

1999-01-01

In summary the tertiary care programs in this nation are trapped in a difficult dilemma. On one side is the ongoing reduction in provider revenue driven by real and powerful market forces. On the other side is a traditional payment system governed by necessary laws that inhibit meaningful re-engineering of tertiary care delivery. If a remedy to this situation cannot be created then it is very likely that all aspects of quality as defined earlier will suffer. It is our hope that by very careful construction of a relationship, with attention to applicable statutes and careful measurement of utilization and quality, a limited business alignment of a hospital and a group of tertiary physicians can be approved in the care of Medicare, Medicaid and all federally funded patients.

Geophysical ore guides along the Colorado mineral belt

USGS Publications Warehouse

Case, James E.

1967-01-01

A 40-50-mgal gravity low trends northeast along the Colorado mineral belt between Monarch Pass and Breckenridge, Colorado. The low is probably caused by a silicic Tertiary batholith of lower density than adjacent Precambrian crystalline rocks. Many major mining districts associated with silicic Tertiary intrusives are near the axis of the low. Positive and negative aeromagnetic anomalies are present over the larger silicic Tertiary intrusive bodies. A good correlation exists between the magnetic lows and zones of altered, mineralized porphyry. Apparently, original magnetite in the silicic porphyries has been altered to relatively nonmagnetic pyrite or iron oxides. The regional gravity low aids in defining the limits of the mineral belt, and the magnetic lows over the porphyries indicate specific alteration zones and the possibility of associated mineral deposits.

Reconnaissance guidelines for gold exploration in Central Alaska

USGS Publications Warehouse

Light, T.D.; Moll, S.H.; Bie, S.W.; Lee, G.K.

1993-01-01

Distribution of more than 300 gold-bearing samples from the Livengood (Tolovana) and parts of the Fairbanks and Rampart mining districts in central Alaska, USA, indicate that the concentration of gold in placers is spatially related both to structural features and to Late Cretaceous and (or) Tertiary felsic plutons. The regional consistency of these spatial relationships is demonstrated by proximity analysis using a Geographic Information System (GIS), and suggests a genetic association between faults, felsic plutons, and gold occurrences. The local presence of gold within several of the plutons indicates that these are the source of some of the gold. In addition, some gold occurs proximal to faults where plutons are not present, suggesting that some of the gold was also derived from the country rock. We envision a model whereby weakly mineralized solutions, thermally driven by latent plutonic heat, were enriched by circulation through clastic units that may have had a naturally elevated gold background. The resultant enriched solutions were channeled and reconcentrated along or adjacent to large-scale fault systems. Future exploration to define individual target areas should be directed toward areas where Late Cretaceous and (or) Tertiary felsic plutons occur near major faults. ?? 1993.

Patients' assessment of quality of care in public tertiary hospitals with and without accreditation: comparative cross-sectional study.

PubMed

Aboshaiqah, Ahmad E; Alonazi, Wadi B; Patalagsa, Joel Gonzales

2016-11-01

To compare patients' assessment of quality of care provided by public tertiary hospitals grouped according to accreditation status. Healthcare institutions worldwide are increasingly adopting accreditation as continuing initiative aimed at improving structures, processes and outcomes associated with quality of care. Patients being recipients of health care need to participate in assessing the quality of care they experienced while confined for therapeutic management. Comparative, cross-sectional. Data were collected from patients confined in public tertiary hospitals (n = 517 in four with accreditation and n = 542 in four without accreditation) in Riyadh, Saudi Arabia between February 2011-June 2011. Patients rated key performance indicators grouped under the dimensions of structure, process and outcome. Mann-Whitney U-test, Spearman Correlation Coefficient and coefficient of determination were used in analysing data. Patients in accredited public tertiary hospitals perceived structure, outcome and overall quality of care statistically higher than patients in non-accredited hospitals. No statistical differences were found in process (access and communication) indicators. Accreditation status is marginally associated with structure; outcome; and overall quality of care. The proportion of variance in the ranks of accreditation status explained the proportion of variance in the ranks of structure; outcome; and overall quality of care. The results apparently showed better structure, outcome and overall quality of care in accredited hospitals. Accreditation's association in the overall quality of care apparently remained unclear. Further studies are needed to appreciate the contribution of accreditation. © 2016 John Wiley & Sons Ltd.

Halogen dependent symmetry change in two series of wheel cluster organic frameworks built from La18 tertiary building units.

PubMed

Fang, Wei-Hui; Zhang, Lei; Zhang, Jian; Yang, Guo-Yu

2016-01-25

Two series of wheel cluster organic frameworks (WCOFs) built from La18 tertiary building units are hydrothermally made, which show halogen-dependent structural symmetry, and demonstrate different chiral performances.

Structural relationships of pre-Tertiary rocks in the Nevada Test Site region, southern Nevada

USGS Publications Warehouse

Cole, James C.; Cashman, Patricia Hughes

1999-01-01

This report contains a synthesis and interpretation of structural and stratigraphic data for pre-Tertiary rocks in a large area of southern Nevada within and near the Nevada Test Site. Its presents descriptive and interpretive information from discontinuously exposed localities in the context of a regional model that integrates stratigraphy, sedimentology, crustal structure, and deformational style and timing. Evidence is given for substantial strike-slip faults, for modest excursion on low-angle faults, and for pre-Oligocene formation of the regional oroclinal flexure in neighboring mountain ranges.

Architecture of a Diels-Alderase ribozyme with a preformed catalytic pocket.

PubMed

Keiper, Sonja; Bebenroth, Dirk; Seelig, Burckhard; Westhof, Eric; Jäschke, Andres

2004-09-01

Artificial ribozymes catalyze a variety of chemical reactions. Their structures and reaction mechanisms are largely unknown. We have analyzed a ribozyme catalyzing Diels-Alder cycloaddition reactions by comprehensive mutation analysis and a variety of probing techniques. New tertiary interactions involving base pairs between nucleotides of the 5' terminus and a large internal loop forming a pseudoknot fold were identified. The probing data indicate a preformed tertiary structure that shows no major changes on substrate or product binding. Based on these observations, a molecular architecture featuring a Y-shaped arrangement is proposed. The tertiary structure is formed in a rather unusual way; that is, the opposite sides of the asymmetric internal loop are clamped by the four 5'-terminal nucleotides, forming two adjacent two base-pair helices. It is proposed that the catalytic pocket is formed by a wedge within one of these helices.

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

Xiong, J.-P.; Stehle, T.; Zhang, R.

The structural basis for the divalent cation-dependent binding of heterodimeric alpha beta integrins to their ligands, which contain the prototypical Arg-Gly-Asp sequence, is unknown. Interaction with ligands triggers tertiary and quaternary structural rearrangements in integrins that are needed for cell signaling. Here we report the crystal structure of the extracellular segment of integrin alpha Vbeta 3 in complex with a cyclic peptide presenting the Arg-Gly-Asp sequence. The ligand binds at the major interface between the alpha V and beta 3 subunits and makes extensive contacts with both. Both tertiary and quaternary changes are observed in the presence of ligand. Themore » tertiary rearrangements take place in beta A, the ligand-binding domain of beta 3; in the complex, beta A acquires two cations, one of which contacts the ligand Asp directly and the other stabilizes the ligand-binding surface. Ligand binding induces small changes in the orientation of alpha V relative to beta 3.« less

Tertiary structure-based analysis of microRNA–target interactions

PubMed Central

Gan, Hin Hark; Gunsalus, Kristin C.

2013-01-01

Current computational analysis of microRNA interactions is based largely on primary and secondary structure analysis. Computationally efficient tertiary structure-based methods are needed to enable more realistic modeling of the molecular interactions underlying miRNA-mediated translational repression. We incorporate algorithms for predicting duplex RNA structures, ionic strength effects, duplex entropy and free energy, and docking of duplex–Argonaute protein complexes into a pipeline to model and predict miRNA–target duplex binding energies. To ensure modeling accuracy and computational efficiency, we use an all-atom description of RNA and a continuum description of ionic interactions using the Poisson–Boltzmann equation. Our method predicts the conformations of two constructs of Caenorhabditis elegans let-7 miRNA–target duplexes to an accuracy of ∼3.8 Å root mean square distance of their NMR structures. We also show that the computed duplex formation enthalpies, entropies, and free energies for eight miRNA–target duplexes agree with titration calorimetry data. Analysis of duplex–Argonaute docking shows that structural distortions arising from single-base-pair mismatches in the seed region influence the activity of the complex by destabilizing both duplex hybridization and its association with Argonaute. Collectively, these results demonstrate that tertiary structure-based modeling of miRNA interactions can reveal structural mechanisms not accessible with current secondary structure-based methods. PMID:23417009

Rapid search for tertiary fragments reveals protein sequence–structure relationships

PubMed Central

Zhou, Jianfu; Grigoryan, Gevorg

2015-01-01

Finding backbone substructures from the Protein Data Bank that match an arbitrary query structural motif, composed of multiple disjoint segments, is a problem of growing relevance in structure prediction and protein design. Although numerous protein structure search approaches have been proposed, methods that address this specific task without additional restrictions and on practical time scales are generally lacking. Here, we propose a solution, dubbed MASTER, that is both rapid, enabling searches over the Protein Data Bank in a matter of seconds, and provably correct, finding all matches below a user-specified root-mean-square deviation cutoff. We show that despite the potentially exponential time complexity of the problem, running times in practice are modest even for queries with many segments. The ability to explore naturally plausible structural and sequence variations around a given motif has the potential to synthesize its design principles in an automated manner; so we go on to illustrate the utility of MASTER to protein structural biology. We demonstrate its capacity to rapidly establish structure–sequence relationships, uncover the native designability landscapes of tertiary structural motifs, identify structural signatures of binding, and automatically rewire protein topologies. Given the broad utility of protein tertiary fragment searches, we hope that providing MASTER in an open-source format will enable novel advances in understanding, predicting, and designing protein structure. PMID:25420575

26 CFR 1.193-1 - Deduction for tertiary injectant expenses.

Code of Federal Regulations, 2010 CFR

2010-04-01

... of section 193 and this section, the term hydrocarbon means all forms of natural gas and crude oil (which includes oil recovered from sources such as oil shale and condensate). (5) Injectant defined. For...

Magnetotelluric Data, Mid Valley, Nevada Test Site, Nevada

USGS Publications Warehouse

Williams, Jackie M.; Wallin, Erin L.; Rodriguez, Brian D.; Lindsey, Charles R.; Sampson, Jay A.

2007-01-01

Introduction The United States Department of Energy (DOE) and the National Nuclear Security Administration (NNSA) at their Nevada Site Office (NSO) are addressing ground-water contamination resulting from historical underground nuclear testing through the Environmental Management (EM) program and, in particular, the Underground Test Area (UGTA) project. One issue of concern is the nature of the somewhat poorly constrained pre-Tertiary geology and its effects on ground-water flow. Ground-water modelers would like to know more about the hydrostratigraphy and geologic structure to support a hydrostratigraphic framework model that is under development for the Rainier Mesa/Shoshone Mountain Corrective Action Unit (CAU). During 2003, the U.S. Geological Survey (USGS), in cooperation with the DOE and NNSA-NSO, collected and processed data at the Nevada Test Site in and near Yucca Flat (YF) to help define the character, thickness, and lateral extent of the pre-Tertiary confining units. We collected 51 magnetotelluric (MT) and audio-magnetotelluric (AMT), stations for that research. In early 2005 we extended that research with 26 additional MT data stations, located on and near Rainier Mesa and Shoshone Mountain (RM-SM). The new stations extended the area of the hydrogeologic study previously conducted in Yucca Flat. This work was done to help refine what is known about the character, thickness, and lateral extent of pre-Tertiary confining units. In particular, a major goal was to define the upper clastic confining unit (UCCU). The UCCU is comprised of late Devonian to Mississippian siliciclastic rocks assigned to the Eleana Formation and Chainman Shale. The UCCU underlies the Yucca Flat area and extends westward towards Shoshone Mountain, southward to Buckboard Mesa, and northward to Rainier Mesa. Late in 2005 we collected another 14 MT stations in Mid Valley and in northern Yucca Flat basin. That work was done to better determine the extent and thickness of the UCCU near the southeastern RM-SM CAU boundary with the southwestern YF CAU, and also in the northern YF CAU. The purpose of this report is to release the MT data at those 14 stations. No interpretation of the data is included here.

Stromal cells in chronic inflammation and tertiary lymphoid organ formation.

PubMed

Buckley, Christopher D; Barone, Francesca; Nayar, Saba; Bénézech, Cecile; Caamaño, Jorge

2015-01-01

Inflammation is an unstable state. It either resolves or persists. Why inflammation persists and the factors that define tissue tropism remain obscure. Increasing evidence suggests that tissue-resident stromal cells not only provide positional memory but also actively regulate the differential accumulation of inflammatory cells within inflamed tissues. Furthermore, at many sites of chronic inflammation, structures that mimic secondary lymphoid tissues are observed, suggesting that chronic inflammation and lymphoid tissue formation share common activation programs. Similarly, blood and lymphatic endothelial cells contribute to tissue homeostasis and disease persistence in chronic inflammation. This review highlights our increasing understanding of the role of stromal cells in inflammation and summarizes the novel immunological role that stromal cells exert in the persistence of inflammatory diseases.

Structures of Staphylococcus aureus D-tagatose-6-phosphate kinase implicate domain motions in specificity and mechanism.

PubMed

Miallau, Linda; Hunter, William N; McSweeney, Sean M; Leonard, Gordon A

2007-07-06

High resolution structures of Staphylococcus aureus d-tagatose-6-phosphate kinase (LacC) in two crystal forms are herein reported. The structures define LacC in apoform, in binary complexes with ADP or the co-factor analogue AMP-PNP, and in a ternary complex with AMP-PNP and D-tagatose-6-phosphate. The tertiary structure of the LacC monomer, which is closely related to other members of the pfkB subfamily of carbohydrate kinases, is composed of a large alpha/beta core domain and a smaller, largely beta "lid." Four extended polypeptide segments connect these two domains. Dimerization of LacC occurs via interactions between lid domains, which come together to form a beta-clasp structure. Residues from both subunits contribute to substrate binding. LacC adopts a closed structure required for phosphoryl transfer only when both substrate and co-factor are bound. A reaction mechanism similar to that used by other phosphoryl transferases is proposed, although unusually, when both substrate and co-factor are bound to the enzyme two Mg(2+) ions are observed in the active site. A new motif of amino acid sequence conservation common to the pfkB subfamily of carbohydrate kinases is identified.

Distinct Tertiary Lymphoid Structure Associations and Their Prognostic Relevance in HER2 Positive and Negative Breast Cancers.

PubMed

Liu, Xia; Tsang, Julia Y S; Hlaing, Thazin; Hu, Jintao; Ni, Yun-Bi; Chan, Siu Ki; Cheung, Sai Yin; Tse, Gary M

2017-11-01

The presence of tumor infiltrating lymphocytes (TIL) is associated with favorable prognosis. Recent evidence suggested that not only their density, but also the spatial organization as tertiary lymphoid structures (TLS), play a key role in determining patient survival. In a cohort of 248 breast cancers, the clinicopathologic association and prognostic role of TLS was examined. Tertiary lymphoid structures were associated with higher tumor grade, apocrine phenotype, necrosis, extensive in situ component, lymphovascular invasion (LVI), and high TIL. For biomarkers, TLS were associated with hormone receptors negativity, HER2 positivity, and c-kit expression. Tertiary lymphoid structures were significantly related to better disease-free survival (DFS) in HER2 positive (HER2+) breast cancers (log-rank = 4.054), which was not dependent on high TIL status. The combined TLS and TIL status was an independent favorable factor associated with DFS in those cases. Interestingly, tumor cell infiltration into the TLS was found in 41.9% of TLS positive cases. It was associated with LVI in HER2 negative (HER2-) TLS positive (particularly estrogen receptor positive [ER+] HER2-) cases. In the ER+ HER2- cases, tumor cell infiltration into TLS was also associated with increased pathologic nodal stage (pN) stage and nodal involvement. Tertiary lymphoid structures showed a similar relationship with clinicopathologic features and biomarkers as TIL. The presence of TLS, irrespective of TIL level, could be an important favorable prognostic indicator in HER2+ breast cancer patients. Given the significance of TLS in promoting effective antitumor immunity, further understanding of its organization and induction may provide new opportunities to improve the current immunotherapy strategies. Despite recent interest on the clinical value of tumor infiltrating lymphocyte (TIL), little was known on the clinical significance on their spatial organization as tertiary lymphoid structures (TLS). Although TLS showed similar relationships with clinicopathologic features and biomarkers as TIL, the prognostic value of TLS, particularly in HER2 positive cancers, was independent of TIL. Moreover, tumor infiltration could be present in TLS which appears to be related to tumor invasion in HER2 negative cancers. Overall, the results demonstrated the additional value for TLS in HER2 cancer subtypes. Further investigations and its standardized evaluation will enhance its use as standard practice. © AlphaMed Press 2017.

Interpretation of a 3D Seismic-Reflection Volume in the Basin and Range, Hawthorne, Nevada

NASA Astrophysics Data System (ADS)

Louie, J. N.; Kell, A. M.; Pullammanappallil, S.; Oldow, J. S.; Sabin, A.; Lazaro, M.

2009-12-01

A collaborative effort by the Great Basin Center for Geothermal Energy at the University of Nevada, Reno, and Optim Inc. of Reno has interpreted a 3d seismic data set recorded by the U.S. Navy Geothermal Programs Office (GPO) at the Hawthorne Army Depot, Nevada. The 3d survey incorporated about 20 NNW-striking lines covering an area of approximately 3 by 10 km. The survey covered an alluvial area below the eastern flank of the Wassuk Range. In the reflection volume the most prominent events are interpreted to be the base of Quaternary alluvium, the Quaternary Wassuk Range-front normal fault zone, and sequences of intercalated Tertiary volcanic flows and sediments. Such a data set is rare in the Basin and Range. Our interpretation reveals structural and stratigraphic details that form a basis for rapid development of the geothermal-energy resources underlying the Depot. We interpret a map of the time-elevation of the Wassuk Range fault and its associated splays and basin-ward step faults. The range-front fault is the deepest, and its isochron map provides essentially a map of "economic basement" under the prospect area. There are three faults that are the most readily picked through vertical sections. The fault reflections show an uncertainty in the time-depth that we can interpret for them of 50 to 200 ms, due to the over-migrated appearance of the processing contractor’s prestack time-migrated data set. Proper assessment of velocities for mitigating the migration artifacts through prestack depth migration is not possible from this data set alone, as the offsets are not long enough for sufficiently deep velocity tomography. The three faults we interpreted appear as gradients in potential-field maps. In addition, the southern boundary of a major Tertiary graben may be seen within the volume as the northward termination of the strong reflections from older Tertiary volcanics. Using a transparent volume view across the survey gives a view of the volcanics in full, providing a clear picture of prominent structures. Potential drill targets and areas of development are defined within the data volume by the intersections of the fault surfaces with the tracked, strong stratigraphic reflections. Target volumes for drilling and development are defined by the intersections of the faults and bright-spot stratigraphy, and their uncertainty bounds. There are a few such intersections present within the 3d volume. Analyzing seismic attributes gives the opportunity to identify characteristics common in geothermal environments.

Prediction of protein tertiary structure from sequences using a very large back-propagation neural network

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

Liu, X.; Wilcox, G.L.

1993-12-31

We have implemented large scale back-propagation neural networks on a 544 node Connection Machine, CM-5, using the C language in MIMD mode. The program running on 512 processors performs backpropagation learning at 0.53 Gflops, which provides 76 million connection updates per second. We have applied the network to the prediction of protein tertiary structure from sequence information alone. A neural network with one hidden layer and 40 million connections is trained to learn the relationship between sequence and tertiary structure. The trained network yields predicted structures of some proteins on which it has not been trained given only their sequences.more » Presentation of the Fourier transform of the sequences accentuates periodicity in the sequence and yields good generalization with greatly increased training efficiency. Training simulations with a large, heterologous set of protein structures (111 proteins from CM-5 time) to solutions with under 2% RMS residual error within the training set (random responses give an RMS error of about 20%). Presentation of 15 sequences of related proteins in a testing set of 24 proteins yields predicted structures with less than 8% RMS residual error, indicating good apparent generalization.« less

Secondary and tertiary isoquinoline alkaloids from Xylopia parviflora.

PubMed

Nishiyama, Yumi; Moriyasu, Masataka; Ichimaru, Momoyo; Iwasa, Kinuko; Kato, Atsushi; Mathenge, Simon G; Chalo Mutiso, Patrick B; Juma, Francis D

2006-12-01

From the secondary and tertiary alkaloidal fractions of the root and the bark of Xylopia parviflora (Annonaceae), the isoquinoline alkaloids, 10,11-dihydroxy-1,2-dimethoxynoraporphine and parvinine were isolated, along with 39 known alkaloids. Their structures were determined on the basis of analysis of spectroscopic data.

Mutational epitope analysis of Pru av 1 and Api g 1, the major allergens of cherry (Prunus avium) and celery (Apium graveolens): correlating IgE reactivity with three-dimensional structure.

PubMed Central

Neudecker, Philipp; Lehmann, Katrin; Nerkamp, Jörg; Haase, Tanja; Wangorsch, Andrea; Fötisch, Kay; Hoffmann, Silke; Rösch, Paul; Vieths, Stefan; Scheurer, Stephan

2003-01-01

Birch pollinosis is often accompanied by adverse reactions to food due to pollen-allergen specific IgE cross-reacting with homologous food allergens. The tertiary structure of Pru av 1, the major cherry (Prunus avium) allergen, for example, is nearly identical with Bet v 1, the major birch (Betula verrucosa) pollen allergen. In order to define cross-reactive IgE epitopes, we generated and analysed mutants of Pru av 1 and Api g 1.0101, the major celery (Apium graveolens) allergen, by immunoblotting, EAST (enzyme allergosorbent test), CD and NMR spectroscopy. The mutation of Glu45 to Trp45 in the P-loop region, a known IgE epitope of Bet v 1, significantly reduced IgE binding to Pru av 1 in a subgroup of cherry-allergic patients. The backbone conformation of Pru av 1 wild-type is conserved in the three-dimensional structure of Pru av 1 Trp45, demonstrating that the side chain of Glu45 is involved in a cross-reactive IgE epitope. Accordingly, for a subgroup of celery-allergic patients, IgE binding to the homologous celery allergen Api g 1.0101 was enhanced by the mutation of Lys44 to Glu. The almost complete loss of IgE reactivity to the Pru av 1 Pro112 mutant is due to disruption of its tertiary structure. Neither the mutation Ala112 nor deletion of the C-terminal residues 155-159 influenced IgE binding to Pru av 1. In conclusion, the structure of the P-loop partially explains the cross-reactivity pattern, and modulation of IgE-binding by site-directed mutagenesis is a promising approach to develop hypo-allergenic variants for patient-tailored specific immunotherapy. PMID:12943529

Conceptual model of the uppermost principal aquifer systems in the Williston and Powder River structural basins, United States and Canada

USGS Publications Warehouse

Long, Andrew J.; Aurand, Katherine R.; Bednar, Jennifer M.; Davis, Kyle W.; McKaskey, Jonathan D.R.G.; Thamke, Joanna N.

2014-01-01

The three uppermost principal aquifer systems of the Northern Great Plains—the glacial, lower Tertiary, and Upper Cretaceous aquifer systems—are described in this report and provide water for irrigation, mining, public and domestic supply, livestock, and industrial uses. These aquifer systems primarily are present in two nationally important fossil-fuelproducing areas: the Williston and Powder River structural basins in the United States and Canada. The glacial aquifer system is contained within glacial deposits that overlie the lower Tertiary and Upper Cretaceous aquifer systems in the northeastern part of the Williston structural basin. Productive sand and gravel aquifers exist within this aquifer system. The Upper Cretaceous aquifer system is contained within bedrock lithostratigraphic units as deep as 2,850 and 8,500 feet below land surface in the Williston and Powder River structural basins, respectively. Petroleum extraction from much deeper formations, such as the Bakken Formation, is rapidly increasing because of recently improved hydraulic fracturing methods that require large volumes of relatively freshwater from shallow aquifers or surface water. Extraction of coalbed natural gas from within the lower Tertiary aquifer system requires removal of large volumes of groundwater to allow degasification. Recognizing the importance of understanding water resources in these energy-rich basins, the U.S. Geological Survey (USGS) Groundwater Resources Program (http://water.usgs.gov/ogw/gwrp/) began a groundwater study of the Williston and Powder River structural basins in 2011 to quantify this groundwater resource, the results of which are described in this report. The overall objective of this study was to characterize, quantify, and provide an improved conceptual understanding of the three uppermost and principal aquifer systems in energy-resource areas of the Northern Great Plains to assist in groundwater-resource management for multiple uses. The study area includes parts of Montana, North Dakota, South Dakota, and Wyoming in the United States and Manitoba and Saskatchewan in Canada. The glacial aquifer system is contained within glacial drift consisting primarily of till, with smaller amounts of glacial outwash sand and gravel deposits. The lower Tertiary and Upper Cretaceous aquifer systems are contained within several formations of the Tertiary and Cretaceous geologic systems, which are hydraulically separated from underlying aquifers by a basal confining unit. The lower Tertiary and Upper Cretaceous aquifer systems each were divided into three hydrogeologic units that correspond to one or more lithostratigraphic units. The period prior to 1960 is defined as the predevelopment period when little groundwater was extracted. From 1960 through 1990, numerous flowing wells were installed near the Yellowstone, Little Missouri and Knife Rivers, resulting in local groundwater declines. Recently developed technologies for the extraction of petroleum resources, which largely have been applied in the study area since about 2005, require millions of gallons of water for construction of each well, with additional water needed for long-term operation; therefore, the potential for an increase in groundwater extraction is high. In this study, groundwater recharge and discharge components were estimated for the period 1981–2005. Groundwater recharge primarily occurs from infiltration of rainfall and snowmelt (precipitation recharge) and infiltration of streams into the ground (stream infiltration). Total estimated recharge to the Williston and Powder River control volumes is 4,560 and 1,500 cubic feet per second, respectively. Estimated precipitation recharge is 26 and 15 percent of total recharge for the Williston and Powder River control volumes, respectively. Estimated stream infiltration is 71 and 80 percent of total recharge for the Williston and Powder River control volumes, respectively. Groundwater discharge primarily is to streams and springs and is estimated to be about 97 and 92 percent of total discharge for the Williston and Powder River control volumes, respectively. Most of the remaining discharge results from pumped and flowing wells. Groundwater flow in the Williston structural basin generally is from the west and southwest toward the east, where discharge to streams occurs. Locally, in the uppermost hydrogeologic units, groundwater generally is unconfined and flows from topographically high to low areas, where discharge to streams occurs. Groundwater flow in the Powder River structural basin generally is toward the north, with local variations, particularly in the upper Fort Union aquifer, where flow is toward streams.

Inpatient antibiotic consumption in a regional secondary hospital in New Zealand.

PubMed

Hopkins, C J

2014-02-01

Reporting of antibiotic consumption in hospitals is a crucial component of antibiotic stewardship, but data from Australasian secondary hospitals are scarce. The hypothesis of this audit is that antibiotic consumption in secondary hospitals would be lower than in tertiary centres. The study aims to present the first published audit of antibiotic consumption from a secondary hospital in New Zealand compared with two tertiary centres. Hospital population-level data were retrospectively accessed to identify all systemic antibiotics dispensed to adult inpatients at Taranaki District Health Board during 2011. Consumption was calculated in defined daily doses per 100 inpatient-days and per 100 admissions, stratified by drug class. Comparison was against published data from two tertiary centres. Total consumption was lower, but that of high-risk antibiotic classes was higher than both tertiary centres. The relative consumption of lincosamides was 4.0 and 2.6 times higher than the two tertiary centres, with an associated 14% incidence of Clostridium difficile associated diarrhoea within 3 months. Our secondary hospital appears to consume the wrong types of antibiotic rather than too much. Data from all Australasian hospitals, stratified by clinical service area and hospital level, are required for clinically relevant benchmarking. © 2014 The Author; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.

Understanding the General Packing Rearrangements Required for Successful Template Based Modeling of Protein Structure from a CASP Experiment

PubMed Central

Day, Ryan; Joo, Hyun; Chavan, Archana; Lennox, Kristin P.; Chen, Ann; Dahl, David B.; Vannucci, Marina; Tsai, Jerry W.

2012-01-01

As an alternative to the common template based protein structure prediction methods based on main-chain position, a novel side-chain centric approach has been developed. Together with a Bayesian loop modeling procedure and a combination scoring function, the Stone Soup algorithm was applied to the CASP9 set of template based modeling targets. Although the method did not generate as large of perturbations to the template structures as necessary, the analysis of the results gives unique insights into the differences in packing between the target structures and their templates. Considerable variation in packing is found between target and template structures even when the structures are close, and this variation is found due to 2 and 3 body packing interactions. Outside the inherent restrictions in packing representation of the PDB, the first steps in correctly defining those regions of variable packing have been mapped primarily to local interactions, as the packing at the secondary and tertiary structure are largely conserved. Of the scoring functions used, a loop scoring function based on water structure exhibited some promise for discrimination. These results present a clear structural path for further development of a side-chain centered approach to template based modeling. PMID:23266765

Understanding the general packing rearrangements required for successful template based modeling of protein structure from a CASP experiment.

PubMed

Day, Ryan; Joo, Hyun; Chavan, Archana C; Lennox, Kristin P; Chen, Y Ann; Dahl, David B; Vannucci, Marina; Tsai, Jerry W

2013-02-01

As an alternative to the common template based protein structure prediction methods based on main-chain position, a novel side-chain centric approach has been developed. Together with a Bayesian loop modeling procedure and a combination scoring function, the Stone Soup algorithm was applied to the CASP9 set of template based modeling targets. Although the method did not generate as large of perturbations to the template structures as necessary, the analysis of the results gives unique insights into the differences in packing between the target structures and their templates. Considerable variation in packing is found between target and template structures even when the structures are close, and this variation is found due to 2 and 3 body packing interactions. Outside the inherent restrictions in packing representation of the PDB, the first steps in correctly defining those regions of variable packing have been mapped primarily to local interactions, as the packing at the secondary and tertiary structure are largely conserved. Of the scoring functions used, a loop scoring function based on water structure exhibited some promise for discrimination. These results present a clear structural path for further development of a side-chain centered approach to template based modeling. Copyright © 2012 Elsevier Ltd. All rights reserved.

Chilean Universities in the Transition to a Market-Driven Policy Regime

ERIC Educational Resources Information Center

Katz, Jorge; Spence, Randy

2009-01-01

This paper briefly reviews the historical development of the university system in Chile, and describes the current structure of funding, supply and demand for tertiary education, research and university services. Both public and private universities in Chile have expanded and restructured, access to tertiary education has improved, and…

Structural basis of DNA folding and recognition in an AMP-DNA aptamer complex: distinct architectures but common recognition motifs for DNA and RNA aptamers complexed to AMP.

PubMed

Lin, C H; Patel, D J

1997-11-01

Structural studies by nuclear magnetic resonance (NMR) of RNA and DNA aptamer complexes identified through in vitro selection and amplification have provided a wealth of information on RNA and DNA tertiary structure and molecular recognition in solution. The RNA and DNA aptamers that target ATP (and AMP) with micromolar affinity exhibit distinct binding site sequences and secondary structures. We report below on the tertiary structure of the AMP-DNA aptamer complex in solution and compare it with the previously reported tertiary structure of the AMP-RNA aptamer complex in solution. The solution structure of the AMP-DNA aptamer complex shows, surprisingly, that two AMP molecules are intercalated at adjacent sites within a rectangular widened minor groove. Complex formation involves adaptive binding where the asymmetric internal bubble of the free DNA aptamer zippers up through formation of a continuous six-base mismatch segment which includes a pair of adjacent three-base platforms. The AMP molecules pair through their Watson-Crick edges with the minor groove edges of guanine residues. These recognition G.A mismatches are flanked by sheared G.A and reversed Hoogsteen G.G mismatch pairs. The AMP-DNA aptamer and AMP-RNA aptamer complexes have distinct tertiary structures and binding stoichiometries. Nevertheless, both complexes have similar structural features and recognition alignments in their binding pockets. Specifically, AMP targets both DNA and RNA aptamers by intercalating between purine bases and through identical G.A mismatch formation. The recognition G.A mismatch stacks with a reversed Hoogsteen G.G mismatch in one direction and with an adenine base in the other direction in both complexes. It is striking that DNA and RNA aptamers selected independently from libraries of 10(14) molecules in each case utilize identical mismatch alignments for molecular recognition with micromolar affinity within binding-site pockets containing common structural elements.

Conformational changes of a chemically modified HRP: formation of a molten globule like structure at pH 5

PubMed Central

Bamdad, Kourosh; Ranjbar, Bijan; Naderi-Manesh, Hossein; Sadeghi, Mehdi

2014-01-01

Horseradish peroxidase is an all alpha-helical enzyme, which widely used in biochemistry applications mainly because of its ability to enhance the weak signals of target molecules. This monomeric heme-containing plant peroxidase is also used as a reagent for the organic synthesis, biotransformation, chemiluminescent assays, immunoassays, bioremediation, and treatment of wastewaters as well. Accordingly, enhancing stability and catalytic activity of this protein for biotechnological uses has been one of the important issues in the field of biological investigations in recent years. In this study, pH-induced structural alterations of native (HRP), and modified (MHRP) forms of Horseradish peroxidase have been investigated. Based on the results, dramatic loss of the tertiary structure and also the enzymatic activity for both forms of enzymes recorded at pH values lower than 6 and higher than 8. Ellipticiy measurements, however, indicated very slight variations in the secondary structure for MHRP at pH 5. Spectroscopic analysis also indicated that melting of the tertiary structure of MHRP at pH 5 starts at around 45 °C, which is associated to the pKa of His 42 that has a serious role in keeping of the heme prostethic group in its native position through natural hydrogen bond network in the enzyme structure. According to our data, a molten globule like structure of a chemically modified form of Horseradish peroxidase at pH 5 with initial steps of conformational transition in tertiary structure with almost no changes in the secondary structure has been detected. Despite of some conformational changes in the tertiary structure of MHRP at pH 5, this modified form still keeps its catalytic activity to some extent besides enhanced thermal stability. These findings also indicated that a molten globular state does not necessarily preclude efficient catalytic activity. PMID:26417287

Modeling Current-Voltage Charateristics of Proteorhodopsin and Bacteriorhodopsin: Towards an Optoelectronics Based on Proteins.

PubMed

Alfinito, Eleonora; Reggiani, Lino

2016-10-01

Current-voltage characteristics of metal-protein-metal structures made of proteorhodopsin and bacteriorhodopsin are modeled by using a percolation-like approach. Starting from the tertiary structure pertaining to the single protein, an analogous resistance network is created. Charge transfer inside the network is described as a sequential tunneling mechanism and the current is calculated for each value of the given voltage. The theory is validated with available experiments, in dark and light. The role of the tertiary structure of the single protein and of the mechanisms responsible for the photo-activity is discussed.

RNA FRABASE 2.0: an advanced web-accessible database with the capacity to search the three-dimensional fragments within RNA structures

PubMed Central

2010-01-01

Background Recent discoveries concerning novel functions of RNA, such as RNA interference, have contributed towards the growing importance of the field. In this respect, a deeper knowledge of complex three-dimensional RNA structures is essential to understand their new biological functions. A number of bioinformatic tools have been proposed to explore two major structural databases (PDB, NDB) in order to analyze various aspects of RNA tertiary structures. One of these tools is RNA FRABASE 1.0, the first web-accessible database with an engine for automatic search of 3D fragments within PDB-derived RNA structures. This search is based upon the user-defined RNA secondary structure pattern. In this paper, we present and discuss RNA FRABASE 2.0. This second version of the system represents a major extension of this tool in terms of providing new data and a wide spectrum of novel functionalities. An intuitionally operated web server platform enables very fast user-tailored search of three-dimensional RNA fragments, their multi-parameter conformational analysis and visualization. Description RNA FRABASE 2.0 has stored information on 1565 PDB-deposited RNA structures, including all NMR models. The RNA FRABASE 2.0 search engine algorithms operate on the database of the RNA sequences and the new library of RNA secondary structures, coded in the dot-bracket format extended to hold multi-stranded structures and to cover residues whose coordinates are missing in the PDB files. The library of RNA secondary structures (and their graphics) is made available. A high level of efficiency of the 3D search has been achieved by introducing novel tools to formulate advanced searching patterns and to screen highly populated tertiary structure elements. RNA FRABASE 2.0 also stores data and conformational parameters in order to provide "on the spot" structural filters to explore the three-dimensional RNA structures. An instant visualization of the 3D RNA structures is provided. RNA FRABASE 2.0 is freely available at http://rnafrabase.cs.put.poznan.pl. Conclusions RNA FRABASE 2.0 provides a novel database and powerful search engine which is equipped with new data and functionalities that are unavailable elsewhere. Our intention is that this advanced version of the RNA FRABASE will be of interest to all researchers working in the RNA field. PMID:20459631

RNA FRABASE 2.0: an advanced web-accessible database with the capacity to search the three-dimensional fragments within RNA structures.

PubMed

Popenda, Mariusz; Szachniuk, Marta; Blazewicz, Marek; Wasik, Szymon; Burke, Edmund K; Blazewicz, Jacek; Adamiak, Ryszard W

2010-05-06

Recent discoveries concerning novel functions of RNA, such as RNA interference, have contributed towards the growing importance of the field. In this respect, a deeper knowledge of complex three-dimensional RNA structures is essential to understand their new biological functions. A number of bioinformatic tools have been proposed to explore two major structural databases (PDB, NDB) in order to analyze various aspects of RNA tertiary structures. One of these tools is RNA FRABASE 1.0, the first web-accessible database with an engine for automatic search of 3D fragments within PDB-derived RNA structures. This search is based upon the user-defined RNA secondary structure pattern. In this paper, we present and discuss RNA FRABASE 2.0. This second version of the system represents a major extension of this tool in terms of providing new data and a wide spectrum of novel functionalities. An intuitionally operated web server platform enables very fast user-tailored search of three-dimensional RNA fragments, their multi-parameter conformational analysis and visualization. RNA FRABASE 2.0 has stored information on 1565 PDB-deposited RNA structures, including all NMR models. The RNA FRABASE 2.0 search engine algorithms operate on the database of the RNA sequences and the new library of RNA secondary structures, coded in the dot-bracket format extended to hold multi-stranded structures and to cover residues whose coordinates are missing in the PDB files. The library of RNA secondary structures (and their graphics) is made available. A high level of efficiency of the 3D search has been achieved by introducing novel tools to formulate advanced searching patterns and to screen highly populated tertiary structure elements. RNA FRABASE 2.0 also stores data and conformational parameters in order to provide "on the spot" structural filters to explore the three-dimensional RNA structures. An instant visualization of the 3D RNA structures is provided. RNA FRABASE 2.0 is freely available at http://rnafrabase.cs.put.poznan.pl. RNA FRABASE 2.0 provides a novel database and powerful search engine which is equipped with new data and functionalities that are unavailable elsewhere. Our intention is that this advanced version of the RNA FRABASE will be of interest to all researchers working in the RNA field.

A DEAD-box RNA helicase promotes thermodynamic equilibration of kinetically trapped RNA structures in vivo.

PubMed

Ruminski, Dana J; Watson, Peter Y; Mahen, Elisabeth M; Fedor, Martha J

2016-03-01

RNAs must assemble into specific structures in order to carry out their biological functions, but in vitro RNA folding reactions produce multiple misfolded structures that fail to exchange with functional structures on biological time scales. We used carefully designed self-cleaving mRNAs that assemble through well-defined folding pathways to identify factors that differentiate intracellular and in vitro folding reactions. Our previous work showed that simple base-paired RNA helices form and dissociate with the same rate and equilibrium constants in vivo and in vitro. However, exchange between adjacent secondary structures occurs much faster in vivo, enabling RNAs to quickly adopt structures with the lowest free energy. We have now used this approach to probe the effects of an extensively characterized DEAD-box RNA helicase, Mss116p, on a series of well-defined RNA folding steps in yeast. Mss116p overexpression had no detectable effect on helix formation or dissociation kinetics or on the stability of interdomain tertiary interactions, consistent with previous evidence that intracellular factors do not affect these folding parameters. However, Mss116p overexpression did accelerate exchange between adjacent helices. The nonprocessive nature of RNA duplex unwinding by DEAD-box RNA helicases is consistent with a branch migration mechanism in which Mss116p lowers barriers to exchange between otherwise stable helices by the melting and annealing of one or two base pairs at interhelical junctions. These results suggest that the helicase activity of DEAD-box proteins like Mss116p distinguish intracellular RNA folding pathways from nonproductive RNA folding reactions in vitro and allow RNA structures to overcome kinetic barriers to thermodynamic equilibration in vivo. © 2016 Ruminski et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Effects of a high-pressure treatment on the wheat alpha-amylase inhibitor and its relationship to elimination of allergenicity

NASA Astrophysics Data System (ADS)

Yamamoto, S.; Takanohashi, K.; Hara, T.; Odani, S.; Suzuki, A.; Nishiumi, T.

2010-03-01

In this study, the effects of high-pressure treatment on structure and allergeincity of alpha amylase inhibitor (a-AI) were investigated. The pressure-induced structural changes of α-AI were estimated by fluorescence spectra and by fourth derivative UV-spectroscopy for probed tyrosine residues and by circular dichroism (CD) spectroscopy. The changes in the tertiary structure detected by fluorescence spectra and by fourth derivative UV-spectroscopy under high pressure were indicated at over 300 MPa. Measurements of CD spectroscopy suggested that the effects of a high-pressure treatment on changes in the secondary structure of α-AI were little. From our results, pressure-induced changes of the α-AI structure were not apparent. On the other hands, the IgE-specific binding activities of pressurized α-AI to sera from allergic patients against wheat, which is estimated by observations of dot-blotting, were decreased by high-pressure treatment. It is known that the pressure-induced elimination of allergenicity is related to the tertiary structural changes of allergen molecules. This study are suspected that the epitopes of α-AI do not contain tyrosine residues, and thus the decrease of IgE-specific binding activities is probably caused by the tertiary structural changes of these parts of α-AI.

From Ramachandran Maps to Tertiary Structures of Proteins.

PubMed

DasGupta, Debarati; Kaushik, Rahul; Jayaram, B

2015-08-27

Sequence to structure of proteins is an unsolved problem. A possible coarse grained resolution to this entails specification of all the torsional (Φ, Ψ) angles along the backbone of the polypeptide chain. The Ramachandran map quite elegantly depicts the allowed conformational (Φ, Ψ) space of proteins which is still very large for the purposes of accurate structure generation. We have divided the allowed (Φ, Ψ) space in Ramachandran maps into 27 distinct conformations sufficient to regenerate a structure to within 5 Å from the native, at least for small proteins, thus reducing the structure prediction problem to a specification of an alphanumeric string, i.e., the amino acid sequence together with one of the 27 conformations preferred by each amino acid residue. This still theoretically results in 27(n) conformations for a protein comprising "n" amino acids. We then investigated the spatial correlations at the two-residue (dipeptide) and three-residue (tripeptide) levels in what may be described as higher order Ramachandran maps, with the premise that the allowed conformational space starts to shrink as we introduce neighborhood effects. We found, for instance, for a tripeptide which potentially can exist in any of the 27(3) "allowed" conformations, three-fourths of these conformations are redundant to the 95% confidence level, suggesting sequence context dependent preferred conformations. We then created a look-up table of preferred conformations at the tripeptide level and correlated them with energetically favorable conformations. We found in particular that Boltzmann probabilities calculated from van der Waals energies for each conformation of tripeptides correlate well with the observed populations in the structural database (the average correlation coefficient is ∼0.8). An alpha-numeric string and hence the tertiary structure can be generated for any sequence from the look-up table within minutes on a single processor and to a higher level of accuracy if secondary structure can be specified. We tested the methodology on 100 small proteins, and in 90% of the cases, a structure within 5 Å is recovered. We thus believe that the method presented here provides the missing link between Ramachandran maps and tertiary structures of proteins. A Web server to convert a tertiary structure to an alphanumeric string and to predict the tertiary structure from the sequence of a protein using the above methodology is created and made freely accessible at http://www.scfbio-iitd.res.in/software/proteomics/rm2ts.jsp.

A new way to see RNA

PubMed Central

Keating, Kevin S.; Humphris, Elisabeth L.; Pyle, Anna Marie

2015-01-01

Unlike proteins, the RNA backbone has numerous degrees of freedom (eight, if one counts the sugar pucker), making RNA modeling, structure building and prediction a multidimensional problem of exceptionally high complexity. And yet RNA tertiary structures are not infinite in their structural morphology; rather, they are built from a limited set of discrete units. In order to reduce the dimensionality of the RNA backbone in a physically reasonable way, a shorthand notation was created that reduced the RNA backbone torsion angles to two (η and θ, analogous to ϕ and ψ in proteins). When these torsion angles are calculated for nucleotides in a crystallographic database and plotted against one another, one obtains a plot analogous to a Ramachandran plot (the η/θ plot), with highly populated and unpopulated regions. Nucleotides that occupy proximal positions on the plot have identical structures and are found in the same units of tertiary structure. In this review, we describe the statistical validation of the η/θ formalism and the exploration of features within the η/θ plot. We also describe the application of the η/θ formalism in RNA motif discovery, structural comparison, RNA structure building and tertiary structure prediction. More than a tool, however, the η/θ formalism has provided new insights into RNA structure itself, revealing its fundamental components and the factors underlying RNA architectural form. PMID:21729350

Use of terbium as a probe of tRNA tertiary structure and folding.

PubMed Central

Hargittai, M R; Musier-Forsyth, K

2000-01-01

Lanthanide metals such as terbium have previously been shown to be useful for mapping metal-binding sites in RNA. Terbium binds to the same sites on RNA as magnesium, however, with a much higher affinity. Thus, low concentrations of terbium ions can easily displace magnesium and promote phosphodiester backbone scission. At higher concentrations, terbium cleaves RNA in a sequence-independent manner, with a preference for single-stranded, non-Watson-Crick base-paired regions. Here, we show that terbium is a sensitive probe of human tRNALys,3 tertiary structure and folding. When 1 microM tRNA is used, the optimal terbium ion concentration for detecting Mg2+-induced tertiary structural changes is 50-60 microM. Using these concentrations of RNA and terbium, a magnesium-dependent folding transition with a midpoint (KMg) of 2.6 mM is observed for unmodified human tRNALys,3. At lower Tb3+ concentrations, cleavage is restricted to nucleotides that constitute specific metal-binding pockets. This small chemical probe should also be useful for detecting protein induced structural changes in RNA. PMID:11105765

MultiSETTER: web server for multiple RNA structure comparison.

PubMed

Čech, Petr; Hoksza, David; Svozil, Daniel

2015-08-12

Understanding the architecture and function of RNA molecules requires methods for comparing and analyzing their tertiary and quaternary structures. While structural superposition of short RNAs is achievable in a reasonable time, large structures represent much bigger challenge. Therefore, we have developed a fast and accurate algorithm for RNA pairwise structure superposition called SETTER and implemented it in the SETTER web server. However, though biological relationships can be inferred by a pairwise structure alignment, key features preserved by evolution can be identified only from a multiple structure alignment. Thus, we extended the SETTER algorithm to the alignment of multiple RNA structures and developed the MultiSETTER algorithm. In this paper, we present the updated version of the SETTER web server that implements a user friendly interface to the MultiSETTER algorithm. The server accepts RNA structures either as the list of PDB IDs or as user-defined PDB files. After the superposition is computed, structures are visualized in 3D and several reports and statistics are generated. To the best of our knowledge, the MultiSETTER web server is the first publicly available tool for a multiple RNA structure alignment. The MultiSETTER server offers the visual inspection of an alignment in 3D space which may reveal structural and functional relationships not captured by other multiple alignment methods based either on a sequence or on secondary structure motifs.

High-Throughput, Data-Rich Cellular RNA Device Engineering

PubMed Central

Townshend, Brent; Kennedy, Andrew B.; Xiang, Joy S.; Smolke, Christina D.

2015-01-01

Methods for rapidly assessing sequence-structure-function landscapes and developing conditional gene-regulatory devices are critical to our ability to manipulate and interface with biology. We describe a framework for engineering RNA devices from preexisting aptamers that exhibit ligand-responsive ribozyme tertiary interactions. Our methodology utilizes cell sorting, high-throughput sequencing, and statistical data analyses to enable parallel measurements of the activities of hundreds of thousands of sequences from RNA device libraries in the absence and presence of ligands. Our tertiary interaction RNA devices exhibit improved performance in terms of gene silencing, activation ratio, and ligand sensitivity as compared to optimized RNA devices that rely on secondary structure changes. We apply our method to building biosensors for diverse ligands and determine consensus sequences that enable ligand-responsive tertiary interactions. These methods advance our ability to develop broadly applicable genetic tools and to elucidate understanding of the underlying sequence-structure-function relationships that empower rational design of complex biomolecules. PMID:26258292

The Development of Adult and Community Education Policy in New Zealand: Insights from Popper

ERIC Educational Resources Information Center

Slater, Gloria

2009-01-01

This paper examines the process by which all post-compulsory education in New Zealand has become integrated under one administrative structure, the Tertiary Education Commission (TEC), with the intention of developing a single coordinated system of tertiary education. In particular, adult and community education (ACE), the least formal and…

PASS Student Leader and Mentor Roles: A Tertiary Leadership Pathway

ERIC Educational Resources Information Center

Skalicky, Jane; Caney, Annaliese

2010-01-01

In relation to developing leadership skills during tertiary studies, this paper considers the leadership pathway afforded by a Peer Assisted Study Sessions (PASS) program which includes the traditional PASS Leader role and a more senior PASS Mentor role. Data was collected using a structured survey with open-ended questions designed to capture the…

Bhageerath-H: A homology/ab initio hybrid server for predicting tertiary structures of monomeric soluble proteins

PubMed Central

2014-01-01

Background The advent of human genome sequencing project has led to a spurt in the number of protein sequences in the databanks. Success of structure based drug discovery severely hinges on the availability of structures. Despite significant progresses in the area of experimental protein structure determination, the sequence-structure gap is continually widening. Data driven homology based computational methods have proved successful in predicting tertiary structures for sequences sharing medium to high sequence similarities. With dwindling similarities of query sequences, advanced homology/ ab initio hybrid approaches are being explored to solve structure prediction problem. Here we describe Bhageerath-H, a homology/ ab initio hybrid software/server for predicting protein tertiary structures with advancing drug design attempts as one of the goals. Results Bhageerath-H web-server was validated on 75 CASP10 targets which showed TM-scores ≥0.5 in 91% of the cases and Cα RMSDs ≤5Å from the native in 58% of the targets, which is well above the CASP10 water mark. Comparison with some leading servers demonstrated the uniqueness of the hybrid methodology in effectively sampling conformational space, scoring best decoys and refining low resolution models to high and medium resolution. Conclusion Bhageerath-H methodology is web enabled for the scientific community as a freely accessible web server. The methodology is fielded in the on-going CASP11 experiment. PMID:25521245

Metamorphic Proteins: Emergence of Dual Protein Folds from One Primary Sequence.

PubMed

Lella, Muralikrishna; Mahalakshmi, Radhakrishnan

2017-06-20

Every amino acid exhibits a different propensity for distinct structural conformations. Hence, decoding how the primary amino acid sequence undergoes the transition to a defined secondary structure and its final three-dimensional fold is presently considered predictable with reasonable certainty. However, protein sequences that defy the first principles of secondary structure prediction (they attain two different folds) have recently been discovered. Such proteins, aptly named metamorphic proteins, decrease the conformational constraint by increasing flexibility in the secondary structure and thereby result in efficient functionality. In this review, we discuss the major factors driving the conformational switch related both to protein sequence and to structure using illustrative examples. We discuss the concept of an evolutionary transition in sequence and structure, the functional impact of the tertiary fold, and the pressure of intrinsic and external factors that give rise to metamorphic proteins. We mainly focus on the major components of protein architecture, namely, the α-helix and β-sheet segments, which are involved in conformational switching within the same or highly similar sequences. These chameleonic sequences are widespread in both cytosolic and membrane proteins, and these folds are equally important for protein structure and function. We discuss the implications of metamorphic proteins and chameleonic peptide sequences in de novo peptide design.

Patent protection for structural genomics-related inventions.

PubMed

Vinarov, Sara D

2003-01-01

Recently there have been some important developments with respect to the patentability of inventions in the field of structural genomics. The leaders of the European Patent Office (EPO), Japan Patent Office (JPO) and the United States Patent Office (USPTO) came together for a trilateral meeting to conduct a comparative study on protein 3-dimensional (3-D) structure related claims in an effort to come to a mutual understanding about the examination of such inventions. The three patent offices were presented with eight different cases: 1) 3-D structural data of a protein per se; 2) computer-readable storage medium encoded with structural data of a protein; 3) protein defined by its tertiary structure; 4) crystals of known proteins; 5) binding pockets and protein domains; 6) and 7) are both directed to in silico screening methods directed to a specific protein; and 8) pharmacophores. The preliminary conclusions reached at the trilateral meeting provide clarity regarding the types of inventions that may be patentable given a specific set of scientific facts in a patent application. Therefore, the guidance provided by this study will help inventors, attorneys and other patent practitioners who file for patent protection on structural genomics-based inventions both here and abroad comply with the patentability requirements of each office.

Aerial gamma ray and magnetic survey: Powder River II Project, Gillette Quadrangle, Wyoming. Final report

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

Not Available

1979-04-01

The Gillette quadrangle in northeastern Wyoming and western South Dakota contains approximately equal portions of the Powder River Basin and the Black Hills Uplift. In these two structures, a relatively thick sequence of Paleozoic and Mesozoic strata represent nearly continuous deposition over the Precambrian basement complex. The Powder River Basin also contains a thick sequence of early Tertiary rocks which cover about 50% of the surface. A stratigraphic sequence from Upper Cretaceous to Precambrian is exposed in the Black Hills Uplift to the east. Magnetic data apparently illustrate the relative depth to the Precambrian crystalline rocks, but only weakly definemore » the boundary between the Powder River Basin and the Black Hills Uplift. The positions of some small isolated Tertiary intrusive bodies in the Black Hills Uplift are relatively well expressed. The Gillette quadrangle has been productive in terms of uranium mining, but its current status is uncertain. The producing uranium deposits occur within the Lower Cretaceous Inyan Kara Group and the Jurassic Morrison Formation in the Black Hills Uplift. Other prospects occur within the Tertiary Wasatch and Fort Union Formations in the Pumpkin Buttes - Turnercrest district, where it extends into the quadrangle from the Newcastle quadrangle to the south. These four formations, all predominantly nonmarine, contain all known uranium deposits in the Gillette quadrangle. A total of 108 groups of sample responses in the uranium window constitute anomalies as defined in Volume I. The anomalies are most frequently found in the Inyan Kara-Morrison, Wasatch and Fort Union Formations. Many anomalies occur over known mines or prospects. Others may result from unmapped uranium mines or areas where material other than uranium is mined. The remainder may relate to natural geologic features.« less

Minor Structural Change to Tertiary Sulfonamide RORc Ligands Led to Opposite Mechanisms of Action

PubMed Central

2014-01-01

A minor structural change to tertiary sulfonamide RORc ligands led to distinct mechanisms of action. Co-crystal structures of two compounds revealed mechanistically consistent protein conformational changes. Optimized phenylsulfonamides were identified as RORc agonists while benzylsulfonamides exhibited potent inverse agonist activity. Compounds behaving as agonists in our biochemical assay also gave rise to an increased production of IL-17 in human PBMCs whereas inverse agonists led to significant suppression of IL-17 under the same assay conditions. The most potent inverse agonist compound showed >180-fold selectivity over the ROR isoforms as well as all other nuclear receptors that were profiled. PMID:25815138

Computational Analysis of the Ligand Binding Site of the Extracellular ATP Receptor, DORN1

DOE PAGES

Nguyen, Cuong The; Tanaka, Kiwamu; Cao, Yangrong; ...

2016-09-01

DORN1 (also known as P2K1) is a plant receptor for extracellular ATP, which belongs to a large gene family of legume-type (L-type) lectin receptor kinases. Extracellular ATP binds to DORN1 with strong affinity through its lectin domain, and the binding triggers a variety of intracellular activities in response to biotic and abiotic stresses. However, information on the tertiary structure of the ligand binding site of DORN1is lacking, which hampers efforts to fully elucidate the mechanism of receptor action. Available data of the crystal structures from more than 50 L-type lectins enable us to perform an in silico study of molecularmore » interaction between DORN1 and ATP. In this study, we employed a computational approach to develop a tertiary structure model of the DORN1 lectin domain. A blind docking analysis demonstrated that ATP binds to a cavity made by four loops (defined as loops A B, C and D) of the DORN1 lectin domain with high affinity. In silico target docking of ATP to the DORN1 binding site predicted interaction with 12 residues, located on the four loops, via hydrogen bonds and hydrophobic interactions. The ATP binding pocket is structurally similar in location to the carbohydrate binding pocket of the canonical L-type lectins. However, four of the residues predicted to interact with ATP are not conserved between DORN1 and the other carbohydrate-binding lectins, suggesting that diversifying selection acting on these key residues may have led to the ATP binding activity of DORN1. Finally, the in silico model was validated by in vitro ATP binding assays using the purified extracellular lectin domain of wild-type DORN1, as well as mutated DORN1 lacking key ATP binding residues.« less

Computational Analysis of the Ligand Binding Site of the Extracellular ATP Receptor, DORN1

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

Nguyen, Cuong The; Tanaka, Kiwamu; Cao, Yangrong

DORN1 (also known as P2K1) is a plant receptor for extracellular ATP, which belongs to a large gene family of legume-type (L-type) lectin receptor kinases. Extracellular ATP binds to DORN1 with strong affinity through its lectin domain, and the binding triggers a variety of intracellular activities in response to biotic and abiotic stresses. However, information on the tertiary structure of the ligand binding site of DORN1is lacking, which hampers efforts to fully elucidate the mechanism of receptor action. Available data of the crystal structures from more than 50 L-type lectins enable us to perform an in silico study of molecularmore » interaction between DORN1 and ATP. In this study, we employed a computational approach to develop a tertiary structure model of the DORN1 lectin domain. A blind docking analysis demonstrated that ATP binds to a cavity made by four loops (defined as loops A B, C and D) of the DORN1 lectin domain with high affinity. In silico target docking of ATP to the DORN1 binding site predicted interaction with 12 residues, located on the four loops, via hydrogen bonds and hydrophobic interactions. The ATP binding pocket is structurally similar in location to the carbohydrate binding pocket of the canonical L-type lectins. However, four of the residues predicted to interact with ATP are not conserved between DORN1 and the other carbohydrate-binding lectins, suggesting that diversifying selection acting on these key residues may have led to the ATP binding activity of DORN1. Finally, the in silico model was validated by in vitro ATP binding assays using the purified extracellular lectin domain of wild-type DORN1, as well as mutated DORN1 lacking key ATP binding residues.« less

Epilepsy in Ireland: towards the primary-tertiary care continuum.

PubMed

Varley, Jarlath; Delanty, Norman; Normand, Charles; Coyne, Imelda; McQuaid, Louise; Collins, Claire; Boland, Michael; Grimson, Jane; Fitzsimons, Mary

2010-01-01

Epilepsy is a chronic neurological disease affecting people of every age, gender, race and socio-economic background. The diagnosis and optimal management relies on contribution from a number of healthcare disciplines in a variety of healthcare settings. To explore the interface between primary care and specialist epilepsy services in Ireland. Using appreciative inquiry, focus groups were held with healthcare professionals (n=33) from both primary and tertiary epilepsy specialist services in Ireland. There are significant challenges to delivering a consistent high standard of epilepsy care in Ireland. The barriers that were identified are: the stigma of epilepsy, unequal access to care services, insufficient human resources, unclear communication between primary-tertiary services and lack of knowledge. Improving the management of people with epilepsy requires reconfiguration of the primary-tertiary interface and establishing clearly defined roles and formalised clinical pathways. Such initiatives require resources in the form of further education and training and increased usage of information communication technology (ICT). Epilepsy services across the primary-tertiary interface can be significantly enhanced through the implementation of a shared model of care underpinned by an electronic patient record (EPR) system and information communication technology (ICT). Better chronic disease management has the potential to halt the progression of epilepsy with ensuing benefits for patients and the healthcare system. Copyright 2009 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Probing RNA Native Conformational Ensembles with Structural Constraints.

PubMed

Fonseca, Rasmus; van den Bedem, Henry; Bernauer, Julie

2016-05-01

Noncoding ribonucleic acids (RNA) play a critical role in a wide variety of cellular processes, ranging from regulating gene expression to post-translational modification and protein synthesis. Their activity is modulated by highly dynamic exchanges between three-dimensional conformational substates, which are difficult to characterize experimentally and computationally. Here, we present an innovative, entirely kinematic computational procedure to efficiently explore the native ensemble of RNA molecules. Our procedure projects degrees of freedom onto a subspace of conformation space defined by distance constraints in the tertiary structure. The dimensionality reduction enables efficient exploration of conformational space. We show that the conformational distributions obtained with our method broadly sample the conformational landscape observed in NMR experiments. Compared to normal mode analysis-based exploration, our procedure diffuses faster through the experimental ensemble while also accessing conformational substates to greater precision. Our results suggest that conformational sampling with a highly reduced but fully atomistic representation of noncoding RNA expresses key features of their dynamic nature.

Curriculum Development in Outdoor Education: Tasmanian Teachers' Perspectives on the New Pre-Tertiary Outdoor Leadership Course

ERIC Educational Resources Information Center

Dyment, Janet; Morse, Marcus; Shaw, Simon; Smith, Heidi

2014-01-01

The paper examines how outdoor education teachers in Tasmania, Australia have implemented and perceive a new pre-tertiary Outdoor Leadership curriculum document. It draws on an analysis of in-depth semi-structured interviews with 11 outdoor education teachers. The results revealed that teachers were generally welcoming of the new higher-order…

Asian Students' Perceptions of Group Work and Group Assignments in a New Zealand Tertiary Institution

ERIC Educational Resources Information Center

Li, Mingsheng; Campbell, Jacqui

2008-01-01

This study, conducted in 2005 in a New Zealand tertiary institution, examines Asian students' perceptions of the much-promulgated cooperative learning concepts in the form of group work and group assignments. Twenty-two Asian students participated in one-hour individual face-to-face semi-structured interviews. The study found that Asian students…

Role of extensional structures on the location of folds and thrusts during tectonic inversion (northern Iberian Chain, Spain)

NASA Astrophysics Data System (ADS)

Cortés, Angel L.; Liesa, Carlos L.; Soria, Ana R.; Meléndez, Alfonso

1999-03-01

The Aguilón Subbasin (NE Spain) was originated daring the Late Jurassic-Early Cretaceous rifting due to the action of large normal faults, probably inherited from Late Variscan fracturing. WNW-ESE normal faults limit two major troughs filled by continental deposits (Valanginian to Early Barremian). NE-SW faults control the location of subsidiary depocenters within these troughs. These basins were weakly inverted during the Tertiary with folds and thrusts striking E-W to WNW-ESE involving the Mesozoic-Tertiary cover with a maximum estimated shortening of about 12 %. Tertiary compression did not produce the total inversion of the Mesozoic basin but extensional structures are responsible for the location of major Tertiary folds. Shortening of the cover during the Tertiary involved both reactivation of some normal faults and development of folds and thrusts nucleated on basement extensional steps. The inversion style depends mainly on the occurrence and geometry of normal faults limiting the basin. Steep normal faults were not reactivated but acted as buttresses to the cover translation. Around these faults, affecting both basement and cover, folds and thrusts were nucleated due to the stress rise in front of major faults. Within the cover, the buttressing against normal faults consists of folding and faulting implying little shortening without development of ceavage or other evidence of internal deformation.

Formation mechanism of NDMA from ranitidine, trimethylamine, and other tertiary amines during chloramination: a computational study.

PubMed

Liu, Yong Dong; Selbes, Meric; Zeng, Chengchu; Zhong, Rugang; Karanfil, Tanju

2014-01-01

Chloramination of drinking waters has been associated with N-nitrosodimethylamine (NDMA) formation as a disinfection byproduct. NDMA is classified as a probable carcinogen and thus its formation during chloramination has recently become the focus of considerable research interest. In this study, the formation mechanisms of NDMA from ranitidine and trimethylamine (TMA), as models of tertiary amines, during chloramination were investigated by using density functional theory (DFT). A new four-step formation pathway of NDMA was proposed involving nucleophilic substitution by chloramine, oxidation, and dehydration followed by nitrosation. The results suggested that nitrosation reaction is the rate-limiting step and determines the NDMA yield for tertiary amines. When 45 other tertiary amines were examined, the proposed mechanism was found to be more applicable to aromatic tertiary amines, and there may be still some additional factors or pathways that need to be considered for aliphatic tertiary amines. The heterolytic ONN(Me)2-R(+) bond dissociation energy to release NDMA and carbocation R(+) was found to be a criterion for evaluating the reactivity of aromatic tertiary amines. A structure-activity study indicates that tertiary amines with benzyl, aromatic heterocyclic ring, and diene-substituted methenyl adjacent to the DMA moiety are potentially significant NDMA precursors. The findings of this study are helpful for understanding NDMA formation mechanism and predicting NDMA yield of a precursor.

Treatment of lymphangiomas with OK-432 (Picibanil) sclerotherapy: a prospective multi-institutional trial.

PubMed

Giguère, Chantal M; Bauman, Nancy M; Sato, Yutaka; Burke, Diane K; Greinwald, John H; Pransky, Seth; Kelley, Peggy; Georgeson, Keith; Smith, Richard J H

2002-10-01

To describe and to determine the robustness of our study evaluating the efficacy of OK-432 (Picibanil) as a therapeutic modality for lymphangiomas. Prospective, randomized trial and parallel-case series at 13 US tertiary care referral centers. Thirty patients diagnosed as having lymphangioma. Ages in 25 ranged from 6 months to 18 years. Twenty-nine had lesions located in the head-and-neck area. Every patient received a 4-dose injection series of OK-432 scheduled 6 to 8 weeks apart unless a contraindication existed or a complete response was observed before completion of all injections. A control group was observed for 6 months. Successful outcome of therapy was defined as a complete or a substantial (>60%) reduction in lymphangioma size as determined by calculated lesion volumes on computed tomographic or magnetic resonance imaging scans. Overall, 19 (86%) of the 22 patients with predominantly macrocystic lymphangiomas had a successful outcome. OK-432 should be efficacious in the treatment of lymphangiomas. Our study design is well structured to clearly define the role of this treatment agent.

GeneSilico protein structure prediction meta-server.

PubMed

Kurowski, Michal A; Bujnicki, Janusz M

2003-07-01

Rigorous assessments of protein structure prediction have demonstrated that fold recognition methods can identify remote similarities between proteins when standard sequence search methods fail. It has been shown that the accuracy of predictions is improved when refined multiple sequence alignments are used instead of single sequences and if different methods are combined to generate a consensus model. There are several meta-servers available that integrate protein structure predictions performed by various methods, but they do not allow for submission of user-defined multiple sequence alignments and they seldom offer confidentiality of the results. We developed a novel WWW gateway for protein structure prediction, which combines the useful features of other meta-servers available, but with much greater flexibility of the input. The user may submit an amino acid sequence or a multiple sequence alignment to a set of methods for primary, secondary and tertiary structure prediction. Fold-recognition results (target-template alignments) are converted into full-atom 3D models and the quality of these models is uniformly assessed. A consensus between different FR methods is also inferred. The results are conveniently presented on-line on a single web page over a secure, password-protected connection. The GeneSilico protein structure prediction meta-server is freely available for academic users at http://genesilico.pl/meta.

GeneSilico protein structure prediction meta-server

PubMed Central

Kurowski, Michal A.; Bujnicki, Janusz M.

2003-01-01

Rigorous assessments of protein structure prediction have demonstrated that fold recognition methods can identify remote similarities between proteins when standard sequence search methods fail. It has been shown that the accuracy of predictions is improved when refined multiple sequence alignments are used instead of single sequences and if different methods are combined to generate a consensus model. There are several meta-servers available that integrate protein structure predictions performed by various methods, but they do not allow for submission of user-defined multiple sequence alignments and they seldom offer confidentiality of the results. We developed a novel WWW gateway for protein structure prediction, which combines the useful features of other meta-servers available, but with much greater flexibility of the input. The user may submit an amino acid sequence or a multiple sequence alignment to a set of methods for primary, secondary and tertiary structure prediction. Fold-recognition results (target-template alignments) are converted into full-atom 3D models and the quality of these models is uniformly assessed. A consensus between different FR methods is also inferred. The results are conveniently presented on-line on a single web page over a secure, password-protected connection. The GeneSilico protein structure prediction meta-server is freely available for academic users at http://genesilico.pl/meta. PMID:12824313

Structural controls on Carlin-type gold mineralization in the gold bar district, Eureka County, Nevada

USGS Publications Warehouse

Yigit, O.; Nelson, E.P.; Hitzman, M.W.; Hofstra, A.H.

2003-01-01

The Gold Bar district in the southern Roberts Mountains, 48 km northwest of Eureka, Nevada, contains one main deposit (Gold Bar), five satellite deposits, and other resources. Approximately 0.5 Moz of gold have been recovered from a resource of 1,639,000 oz of gold in Carlin-type gold deposits in lower plate, miogeoclinal carbonate rocks below the Roberts Mountains thrust. Host rocks are unit 2 of the Upper Member of the Devonian Denay Formation and the Bartine Member of the McColley Canyon Formation. Spatial and temporal relations between structures and gold mineralization indicate that both pre-Tertiary and Tertiary structures were important controls on gold mineralization. Gold mineralization occurs primarily along high-angle Tertiary normal faults, some of which are reactivated reverse faults of Paleozoic or Mesozoic age. Most deposits are localized at the intersection of northwest- and northeast-striking faults. Alteration includes decalcification, and to a lesser extent, silicification along high-angle faults. Jasperoid (pervasive silicification), which formed along most faults and in some strata-bound zones, accounts for a small portion of the ore in every deposit. In the Gold Canyon deposit, a high-grade jasperoid pipe formed along a Tertiary normal fault which was localized along a zone of overturned fault-propagation folds and thrust faults of Paleozoic or Mesozoic age.

The higher structure of chromatin in the LCR of the beta-globin locus changes during development.

PubMed

Fang, Xiangdong; Yin, Wenxuan; Xiang, Ping; Han, Hemei; Stamatoyannopoulos, George; Li, Qiliang

2009-11-27

The beta-globin locus control region (LCR) is able to enhance the expression of all globin genes throughout the course of development. However, the chromatin structure of the LCR at the different developmental stages is not well defined. We report DNase I and micrococcal nuclease hypersensitivity, chromatin immunoprecipitation analyses for histones H2A, H2B, H3, and H4, and 3C (chromatin conformation capture) assays of the normal and mutant beta-globin loci, which demonstrate that nucleosomes at the DNase I hypersensitive sites of the LCR could be either depleted or retained depending on the stages of development. Furthermore, MNase sensitivity and 3C assays suggest that the LCR chromatin is more open in embryonic erythroblasts than in definitive erythroblasts at the primary- and secondary-structure levels; however, the LCR chromatin is packaged more tightly in embryonic erythroblasts than in definitive erythroblasts at the tertiary chromatin level. Our study provides the first evidence that the occupancy of nucleosomes at a DNase I hypersensitive site is a developmental stage-related event and that embryonic and adult cells possess distinct chromatin structures of the LCR.

Developing an International Corpus of Creative English

ERIC Educational Resources Information Center

Hassall, Peter John

2006-01-01

This paper proposes an International Corpus of Creative English (ICCE) as a worldwide corpus particularly suitable for implementation in countries which have tertiary institutions with well-defined populations of students possessing similar cultural and/or linguistic backgrounds. The ICCE is contextualized as a world Englishes corpus with…

Evaporite geometries and diagenetic traps, lower San Andres, Northwest shelf, New Mexico

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

Keller, D.R.

An east-west-trending belt of lower San Andres oil fields extends 80 mi across southeastern New Mexico from the Pecos River near Roswell to the Texas-New Mexico border. These fields are along a porosity pinch-out zone where porous carbonates grade laterally into bedded anhydrite and halite. The lower San Andres traps are associated with pre-Tertiary structural or stratigraphic traps. Oil and water production relationships from these fields are not consistent with present-day structure. These fields have been commonly interpreted to be hydrodynamic traps created by the eastern flow of fresh surface water that enters the lower San Andres outcrops west ofmore » Pecos River. There is no evidence, however, that surface water has moved through the lower San Andres in this area. This conclusion is supported by the fact that formation-water resistivities are uniform throughout the producing trend, no significant dissolution of carbonates or evaporites has occurred, and there has been no increase in biogradation of oils adjacent to the lower San Andres outcrops. These fields actually are diagenetic traps created by porosity occlusion in the water column beneath the oil accumulations. Hydrocarbons originally were trapped in pre-Tertiary structural and structural-stratigraphic traps. Bedded evaporites were effective barriers to vertical and lateral hydrocarbon migration. Eastward tilting of the Northwest shelf during the Tertiary opened these traps, but the oil remained in these structurally unfavorable positions because of the diagenetic sealing. The gas-solution drive in these reservoirs is a result of this sealing. The sequence of events leading to diagenetic entrapment include (1) Triassic and Jurassic migration of hydrocarbons into broad, low-relief post-San Andres structural and structural-stratigraphic traps; (2) rapid occlusion of porosity in the water column beneath oil reservoirs, and (3) Tertiary tilt-out traps.« less

Discovery of Tertiary Sulfonamides as Potent Liver X Receptor Antagonists

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

Zuercher, William J.; Buckholz†, Richard G.; Campobasso, Nino

2010-08-12

Tertiary sulfonamides were identified in a HTS as dual liver X receptor (LXR, NR1H2, and NR1H3) ligands, and the binding affinity of the series was increased through iterative analogue synthesis. A ligand-bound cocrystal structure was determined which elucidated key interactions for high binding affinity. Further characterization of the tertiary sulfonamide series led to the identification of high affinity LXR antagonists. GSK2033 (17) is the first potent cell-active LXR antagonist described to date. 17 may be a useful chemical probe to explore the cell biology of this orphan nuclear receptor.

Discovery of tertiary sulfonamides as potent liver X receptor antagonists.

PubMed

Zuercher, William J; Buckholz, Richard G; Campobasso, Nino; Collins, Jon L; Galardi, Cristin M; Gampe, Robert T; Hyatt, Stephen M; Merrihew, Susan L; Moore, John T; Oplinger, Jeffrey A; Reid, Paul R; Spearing, Paul K; Stanley, Thomas B; Stewart, Eugene L; Willson, Timothy M

2010-04-22

Tertiary sulfonamides were identified in a HTS as dual liver X receptor (LXR, NR1H2, and NR1H3) ligands, and the binding affinity of the series was increased through iterative analogue synthesis. A ligand-bound cocrystal structure was determined which elucidated key interactions for high binding affinity. Further characterization of the tertiary sulfonamide series led to the identification of high affinity LXR antagonists. GSK2033 (17) is the first potent cell-active LXR antagonist described to date. 17 may be a useful chemical probe to explore the cell biology of this orphan nuclear receptor.

Tertiary alphabet for the observable protein structural universe.

PubMed

Mackenzie, Craig O; Zhou, Jianfu; Grigoryan, Gevorg

2016-11-22

Here, we systematically decompose the known protein structural universe into its basic elements, which we dub tertiary structural motifs (TERMs). A TERM is a compact backbone fragment that captures the secondary, tertiary, and quaternary environments around a given residue, comprising one or more disjoint segments (three on average). We seek the set of universal TERMs that capture all structure in the Protein Data Bank (PDB), finding remarkable degeneracy. Only ∼600 TERMs are sufficient to describe 50% of the PDB at sub-Angstrom resolution. However, more rare geometries also exist, and the overall structural coverage grows logarithmically with the number of TERMs. We go on to show that universal TERMs provide an effective mapping between sequence and structure. We demonstrate that TERM-based statistics alone are sufficient to recapitulate close-to-native sequences given either NMR or X-ray backbones. Furthermore, sequence variability predicted from TERM data agrees closely with evolutionary variation. Finally, locations of TERMs in protein chains can be predicted from sequence alone based on sequence signatures emergent from TERM instances in the PDB. For multisegment motifs, this method identifies spatially adjacent fragments that are not contiguous in sequence-a major bottleneck in structure prediction. Although all TERMs recur in diverse proteins, some appear specialized for certain functions, such as interface formation, metal coordination, or even water binding. Structural biology has benefited greatly from previously observed degeneracies in structure. The decomposition of the known structural universe into a finite set of compact TERMs offers exciting opportunities toward better understanding, design, and prediction of protein structure.

Tertiary alphabet for the observable protein structural universe

PubMed Central

Mackenzie, Craig O.; Zhou, Jianfu; Grigoryan, Gevorg

2016-01-01

Here, we systematically decompose the known protein structural universe into its basic elements, which we dub tertiary structural motifs (TERMs). A TERM is a compact backbone fragment that captures the secondary, tertiary, and quaternary environments around a given residue, comprising one or more disjoint segments (three on average). We seek the set of universal TERMs that capture all structure in the Protein Data Bank (PDB), finding remarkable degeneracy. Only ∼600 TERMs are sufficient to describe 50% of the PDB at sub-Angstrom resolution. However, more rare geometries also exist, and the overall structural coverage grows logarithmically with the number of TERMs. We go on to show that universal TERMs provide an effective mapping between sequence and structure. We demonstrate that TERM-based statistics alone are sufficient to recapitulate close-to-native sequences given either NMR or X-ray backbones. Furthermore, sequence variability predicted from TERM data agrees closely with evolutionary variation. Finally, locations of TERMs in protein chains can be predicted from sequence alone based on sequence signatures emergent from TERM instances in the PDB. For multisegment motifs, this method identifies spatially adjacent fragments that are not contiguous in sequence—a major bottleneck in structure prediction. Although all TERMs recur in diverse proteins, some appear specialized for certain functions, such as interface formation, metal coordination, or even water binding. Structural biology has benefited greatly from previously observed degeneracies in structure. The decomposition of the known structural universe into a finite set of compact TERMs offers exciting opportunities toward better understanding, design, and prediction of protein structure. PMID:27810958

Methods for selecting fixed-effect models for heterogeneous codon evolution, with comments on their application to gene and genome data.

PubMed

Bao, Le; Gu, Hong; Dunn, Katherine A; Bielawski, Joseph P

2007-02-08

Models of codon evolution have proven useful for investigating the strength and direction of natural selection. In some cases, a priori biological knowledge has been used successfully to model heterogeneous evolutionary dynamics among codon sites. These are called fixed-effect models, and they require that all codon sites are assigned to one of several partitions which are permitted to have independent parameters for selection pressure, evolutionary rate, transition to transversion ratio or codon frequencies. For single gene analysis, partitions might be defined according to protein tertiary structure, and for multiple gene analysis partitions might be defined according to a gene's functional category. Given a set of related fixed-effect models, the task of selecting the model that best fits the data is not trivial. In this study, we implement a set of fixed-effect codon models which allow for different levels of heterogeneity among partitions in the substitution process. We describe strategies for selecting among these models by a backward elimination procedure, Akaike information criterion (AIC) or a corrected Akaike information criterion (AICc). We evaluate the performance of these model selection methods via a simulation study, and make several recommendations for real data analysis. Our simulation study indicates that the backward elimination procedure can provide a reliable method for model selection in this setting. We also demonstrate the utility of these models by application to a single-gene dataset partitioned according to tertiary structure (abalone sperm lysin), and a multi-gene dataset partitioned according to the functional category of the gene (flagellar-related proteins of Listeria). Fixed-effect models have advantages and disadvantages. Fixed-effect models are desirable when data partitions are known to exhibit significant heterogeneity or when a statistical test of such heterogeneity is desired. They have the disadvantage of requiring a priori knowledge for partitioning sites. We recommend: (i) selection of models by using backward elimination rather than AIC or AICc, (ii) use a stringent cut-off, e.g., p = 0.0001, and (iii) conduct sensitivity analysis of results. With thoughtful application, fixed-effect codon models should provide a useful tool for large scale multi-gene analyses.

Topological Constraints and Their Conformational Entropic Penalties on RNA Folds.

PubMed

Mak, Chi H; Phan, Ethan N H

2018-05-08

Functional RNAs can fold into intricate structures using a number of different secondary and tertiary structural motifs. Many factors contribute to the overall free energy of the target fold. This study aims at quantifying the entropic costs coming from the loss of conformational freedom when the sugar-phosphate backbone is subjected to constraints imposed by secondary and tertiary contacts. Motivated by insights from topology theory, we design a diagrammatic scheme to represent different types of RNA structures so that constraints associated with a folded structure may be segregated into mutually independent subsets, enabling the total conformational entropy loss to be easily calculated as a sum of independent terms. We used high-throughput Monte Carlo simulations to simulate large ensembles of single-stranded RNA sequences in solution to validate the assumptions behind our diagrammatic scheme, examining the entropic costs for hairpin initiation and formation of many multiway junctions. Our diagrammatic scheme aids in the factorization of secondary/tertiary constraints into distinct topological classes and facilitates the discovery of interrelationships among multiple constraints on RNA folds. This perspective, which to our knowledge is novel, leads to useful insights into the inner workings of some functional RNA sequences, demonstrating how they might operate by transforming their structures among different topological classes. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Alteration of human serum albumin tertiary structure induced by glycation. Spectroscopic study

NASA Astrophysics Data System (ADS)

Szkudlarek, A.; Maciążek-Jurczyk, M.; Chudzik, M.; Równicka-Zubik, J.; Sułkowska, A.

2016-01-01

The modification of human serum albumin (HSA) structure by non-enzymatic glycation is one of the underlying factors that contribute to the development of complications of diabetes and neurodegenerative diseases. The aim of the present work was to estimate how glycation of HSA altered its tertiary structure. Changes of albumin conformation were investigated by comparison of glycated (gHSA) and non-glycated human serum albumin (HSA) absorption spectra, red edge excitation shift (REES) and synchronous spectra. Effect of glycation on human serum albumin tertiary structure was also investigated by 1H NMR spectroscopy. Formation of gHSA Advanced Glycation End-products (AGEs) caused absorption of UV-VIS light between 310 nm and 400 nm while for non-glycated HSA in this region no absorbance has been registered. Analysis of red edge excitation shift effect allowed for observation of structural changes of gHSA in the hydrophobic pocket containing the tryptophanyl residue. Moreover changes in the microenvironment of tryptophanyl and tyrosyl residues brought about AGEs on the basis of synchronous fluorescence spectroscopy have been confirmed. The influence of glycation process on serum albumin binding to 5-dimethylaminonaphthalene-1-sulfonamide (DNSA), 2-(p-toluidino) naphthalene-6-sulfonic acid (TNS), has been studied. Fluorescence analysis showed that environment of both binding site I and II is modified by galactose glycation.

Protein domain definition should allow for conditional disorder

PubMed Central

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

2013-01-01

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

SITEX 2.0: Projections of protein functional sites on eukaryotic genes. Extension with orthologous genes.

PubMed

Medvedeva, Irina V; Demenkov, Pavel S; Ivanisenko, Vladimir A

2017-04-01

Functional sites define the diversity of protein functions and are the central object of research of the structural and functional organization of proteins. The mechanisms underlying protein functional sites emergence and their variability during evolution are distinguished by duplication, shuffling, insertion and deletion of the exons in genes. The study of the correlation between a site structure and exon structure serves as the basis for the in-depth understanding of sites organization. In this regard, the development of programming resources that allow the realization of the mutual projection of exon structure of genes and primary and tertiary structures of encoded proteins is still the actual problem. Previously, we developed the SitEx system that provides information about protein and gene sequences with mapped exon borders and protein functional sites amino acid positions. The database included information on proteins with known 3D structure. However, data with respect to orthologs was not available. Therefore, we added the projection of sites positions to the exon structures of orthologs in SitEx 2.0. We implemented a search through database using site conservation variability and site discontinuity through exon structure. Inclusion of the information on orthologs allowed to expand the possibilities of SitEx usage for solving problems regarding the analysis of the structural and functional organization of proteins. Database URL: http://www-bionet.sscc.ru/sitex/ .

Tertiary structural propensities reveal fundamental sequence/structure relationships.

PubMed

Zheng, Fan; Zhang, Jian; Grigoryan, Gevorg

2015-05-05

Extracting useful generalizations from the continually growing Protein Data Bank (PDB) is of central importance. We hypothesize that the PDB contains valuable quantitative information on the level of local tertiary structural motifs (TERMs). We show that by breaking a protein structure into its constituent TERMs, and querying the PDB to characterize the natural ensemble matching each, we can estimate the compatibility of the structure with a given amino acid sequence through a metric we term "structure score." Considering submissions from recent Critical Assessment of Structure Prediction (CASP) experiments, we found a strong correlation (R = 0.69) between structure score and model accuracy, with poorly predicted regions readily identifiable. This performance exceeds that of leading atomistic statistical energy functions. Furthermore, TERM-based analysis of two prototypical multi-state proteins rapidly produced structural insights fully consistent with prior extensive experimental studies. We thus find that TERM-based analysis should have considerable utility for protein structural biology. Copyright © 2015 Elsevier Ltd. All rights reserved.

Defining an essence of structure determining residue contacts in proteins.

PubMed

Sathyapriya, R; Duarte, Jose M; Stehr, Henning; Filippis, Ioannis; Lappe, Michael

2009-12-01

The network of native non-covalent residue contacts determines the three-dimensional structure of a protein. However, not all contacts are of equal structural significance, and little knowledge exists about a minimal, yet sufficient, subset required to define the global features of a protein. Characterisation of this "structural essence" has remained elusive so far: no algorithmic strategy has been devised to-date that could outperform a random selection in terms of 3D reconstruction accuracy (measured as the Ca RMSD). It is not only of theoretical interest (i.e., for design of advanced statistical potentials) to identify the number and nature of essential native contacts-such a subset of spatial constraints is very useful in a number of novel experimental methods (like EPR) which rely heavily on constraint-based protein modelling. To derive accurate three-dimensional models from distance constraints, we implemented a reconstruction pipeline using distance geometry. We selected a test-set of 12 protein structures from the four major SCOP fold classes and performed our reconstruction analysis. As a reference set, series of random subsets (ranging from 10% to 90% of native contacts) are generated for each protein, and the reconstruction accuracy is computed for each subset. We have developed a rational strategy, termed "cone-peeling" that combines sequence features and network descriptors to select minimal subsets that outperform the reference sets. We present, for the first time, a rational strategy to derive a structural essence of residue contacts and provide an estimate of the size of this minimal subset. Our algorithm computes sparse subsets capable of determining the tertiary structure at approximately 4.8 A Ca RMSD with as little as 8% of the native contacts (Ca-Ca and Cb-Cb). At the same time, a randomly chosen subset of native contacts needs about twice as many contacts to reach the same level of accuracy. This "structural essence" opens new avenues in the fields of structure prediction, empirical potentials and docking.

Defining an Essence of Structure Determining Residue Contacts in Proteins

PubMed Central

Sathyapriya, R.; Duarte, Jose M.; Stehr, Henning; Filippis, Ioannis; Lappe, Michael

2009-01-01

The network of native non-covalent residue contacts determines the three-dimensional structure of a protein. However, not all contacts are of equal structural significance, and little knowledge exists about a minimal, yet sufficient, subset required to define the global features of a protein. Characterisation of this “structural essence” has remained elusive so far: no algorithmic strategy has been devised to-date that could outperform a random selection in terms of 3D reconstruction accuracy (measured as the Ca RMSD). It is not only of theoretical interest (i.e., for design of advanced statistical potentials) to identify the number and nature of essential native contacts—such a subset of spatial constraints is very useful in a number of novel experimental methods (like EPR) which rely heavily on constraint-based protein modelling. To derive accurate three-dimensional models from distance constraints, we implemented a reconstruction pipeline using distance geometry. We selected a test-set of 12 protein structures from the four major SCOP fold classes and performed our reconstruction analysis. As a reference set, series of random subsets (ranging from 10% to 90% of native contacts) are generated for each protein, and the reconstruction accuracy is computed for each subset. We have developed a rational strategy, termed “cone-peeling” that combines sequence features and network descriptors to select minimal subsets that outperform the reference sets. We present, for the first time, a rational strategy to derive a structural essence of residue contacts and provide an estimate of the size of this minimal subset. Our algorithm computes sparse subsets capable of determining the tertiary structure at approximately 4.8 Å Ca RMSD with as little as 8% of the native contacts (Ca-Ca and Cb-Cb). At the same time, a randomly chosen subset of native contacts needs about twice as many contacts to reach the same level of accuracy. This “structural essence” opens new avenues in the fields of structure prediction, empirical potentials and docking. PMID:19997489

The Relevance of English Language Instruction in a Changing Linguistic Environment in Iceland: The L2 Self of Young Icelanders

ERIC Educational Resources Information Center

Jeeves, Anna

2014-01-01

In this study perceptions of post-compulsory school studies in Iceland were investigated through semi-structured interviews. While colloquial English suffices for entertainment, hobbies and Internet use in Iceland, a high level of proficiency is required for employment and tertiary study. School learners and young people in tertiary study and…

EFFECT OF STRUCTURED PHYSICAL ACTIVITY ON SLEEP-WAKE BEHAVIORS IN SEDENTARY ELDERS WITH MOBILITY LIMITATIONS

PubMed Central

Vaz Fragoso, Carlos A.; Miller, Michael E.; King, Abby C.; Kritchevsky, Stephen B.; Liu, Christine K.; Myers, Valerie H.; Nadkarni, Neelesh K.; Pahor, Marco; Spring, Bonnie J.; Gill, Thomas M.

2016-01-01

OBJECTIVE To evaluate the effect of structured physical activity on sleep-wake behaviors in sedentary community-dwelling elders with mobility limitations. DESIGN Multicenter, randomized trial of moderate-intensity physical activity versus health education, with sleep-wake behaviors pre-specified as a tertiary outcome over a planned intervention period ranging between 24 and 30 months. SETTING Lifestyle Interventions and Independence in Elder (LIFE) Study. PARTICIPANTS 1635 community-dwelling persons, aged 70–89 years, who were initially sedentary with a Short Physical Performance Battery score <10. MEASUREMENTS Sleep-wake behaviors were evaluated by the Insomnia Severity Index (ISI) (≥8 defined insomnia), Epworth Sleepiness Scale (ESS) (≥10 defined daytime drowsiness), and Pittsburgh Sleep Quality Index (PSQI) (> 5 defined poor sleep quality) — administered at baseline and subsequently at 6, 18, and 30 months. RESULTS The randomized groups were similar on baseline demographic variables, including mean age (79 years) and sex (67% female). Relative to health education, structured physical activity significantly reduced the likelihood of having poor sleep quality (adjusted odds ratios [adjOR] for PSQI >5 of 0.80 [0.68, 0.94]), including a reduction in new cases (adjOR for PSQI >5 of 0.70 [0.54, 0.89]) but not in resolution of prevalent cases (adjOR for PSQI ≤5 of 1.13 [0.90, 1.43]). No significant intervention effects were observed for ISI or ESS. CONCLUSION Structured physical activity reduced the likelihood of developing poor sleep quality (PSQI >5) over the intervention period, when compared with health education, but had no effect on prevalent cases of poor sleep quality, or on sleep-wake behaviors evaluated by the ISI or ESS. These results suggest that the benefit of physical activity in this sample was preventive and limited to sleep-wake behaviors evaluated by the PSQI. PMID:26115386

Effect of Structured Physical Activity on Sleep-Wake Behaviors in Sedentary Elderly Adults with Mobility Limitations.

PubMed

Vaz Fragoso, Carlos A; Miller, Michael E; King, Abby C; Kritchevsky, Stephen B; Liu, Christine K; Myers, Valerie H; Nadkarni, Neelesh K; Pahor, Marco; Spring, Bonnie J; Gill, Thomas M

2015-07-01

To evaluate the effect of structured physical activity on sleep-wake behaviors in sedentary community-dwelling elderly adults with mobility limitations. Multicenter, randomized trial of moderate-intensity physical activity versus health education, with sleep-wake behaviors prespecified as a tertiary outcome over a planned intervention period ranging from 24 to 30 months. Lifestyle Interventions and Independence for Elders Study. Community-dwelling persons aged 70 to 89 who were initially sedentary and had a Short Physical Performance Battery score less than 10 (N = 1,635). Sleep-wake behaviors were evaluated using the Insomnia Severity Index (ISI) (≥8 defined insomnia), Epworth Sleepiness Scale (ESS) (≥10 defined daytime drowsiness), and Pittsburgh Sleep Quality Index (PSQI) (>5 defined poor sleep quality) administered at baseline and 6, 18, and 30 months. The randomized groups were similar in terms of baseline demographic variables, including mean age (79) and sex (67% female). Structured physical activity resulted in a significantly lower likelihood of having poor sleep quality (adjusted odds ratios (aOR) for PSQI >5 = 0.80, 95% confidence interval (CI) = 0.68-0.94), including fewer new cases (aOR for PSQI >5 = 0.70, 95% CI = 0.54-0.89), than health education but not in resolution of prevalent cases (aOR for PSQI ≤5 = 1.13, 95% CI = 0.90-1.43). No significant intervention effects were observed for the ISI or ESS. Structured physical activity resulted in a lower likelihood of developing poor sleep quality (PSQI >5) over the intervention period than health education but had no effect on prevalent cases of poor sleep quality or on sleep-wake behaviors evaluated using the ISI or ESS. These results suggest that the benefit of physical activity in this sample was preventive and limited to sleep-wake behaviors evaluated using the PSQI. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.

Geology of drill hole UE25p No. 1: A test hole into pre-Tertiary rocks near Yucca Mountain, southern Nevada

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

Carr, M.D.; Waddell, S.J.; Vick, G.S.

1986-12-31

Yucca Mountain in southern Nye County, Nevada, has been proposed as a potential site for the underground disposal of high-level nuclear waste. An exploratory drill hole designated UE25p No. 1 was drilled 3 km east of the proposed repository site to investigate the geology and hydrology of the rocks that underlie the Tertiary volcanic and sedimentary rock sequence forming Yucca Mountain. Silurian dolomite assigned to the Roberts Mountain and Lone Mountain Formations was intersected below the Tertiary section between a depth of approximately 1244 m (4080 ft) and the bottom of the drill hole at 1807 m (5923 ft). Thesemore » formations are part of an important regional carbonate aquifer in the deep ground-water system. Tertiary units deeper than 1139 m (3733 ft) in drill hole UE25p No. 1 are stratigraphically older than any units previously penetrated by drill holes at Yucca Mountain. These units are, in ascending order, the tuff of Yucca Flat, an unnamed calcified ash-flow tuff, and a sequence of clastic deposits. The upper part of the Tertiary sequence in drill hole UE25p No. 1 is similar to that found in other drill holes at Yucca Mountain. The Tertiary sequence is in fault contact with the Silurian rocks. This fault between Tertiary and Paleozoic rocks may correlate with the Fran Ridge fault, a steeply westward-dipping fault exposed approximately 0.5 km east of the drill hole. Another fault intersects UE25p No. 1 at 873 m (2863 ft), but its surface trace is concealed beneath the valley west of the Fran Ridge fault. The Paintbrush Canyon fault, the trace of which passes less than 100 m (330 ft) east of the drilling site, intersects drill hole UE25p No. 1 at a depth of approximately 78 m (255 ft). The drill hole apparently intersected the west flank of a structural high of pre-Tertiary rocks, near the eastern edge of the Crater Flat structural depression.« less

On Chinese Culture Curriculum Planning

ERIC Educational Resources Information Center

Wang, Catherine

2006-01-01

The importance of cultural elements in foreign language teaching has been widely accepted in recent years. This applies particularly to the teaching of Chinese as a foreign language (TCFL) to non-native Chinese speakers at tertiary level in mainland China. However, there is no commonly accepted blueprint that defines the parts of Chinese culture…

Beyond Cliche--Reclaiming the Concept of Sustainability

ERIC Educational Resources Information Center

Fuller, Robert J.

2010-01-01

In closing his 2008 Myer Lecture, the scientist and environmentalist Dr. Tim Flannery said that this century will be defined by the search for sustainability. How perilous therefore that nowadays there is so much overuse of the word "sustainability" that it has become a cliche. Today's tertiary students studying architecture and…

Protein sectors: evolutionary units of three-dimensional structure

PubMed Central

Halabi, Najeeb; Rivoire, Olivier; Leibler, Stanislas; Ranganathan, Rama

2011-01-01

Proteins display a hierarchy of structural features at primary, secondary, tertiary, and higher-order levels, an organization that guides our current understanding of their biological properties and evolutionary origins. Here, we reveal a structural organization distinct from this traditional hierarchy by statistical analysis of correlated evolution between amino acids. Applied to the S1A serine proteases, the analysis indicates a decomposition of the protein into three quasi-independent groups of correlated amino acids that we term “protein sectors”. Each sector is physically connected in the tertiary structure, has a distinct functional role, and constitutes an independent mode of sequence divergence in the protein family. Functionally relevant sectors are evident in other protein families as well, suggesting that they may be general features of proteins. We propose that sectors represent a structural organization of proteins that reflects their evolutionary histories. PMID:19703402

Magnetotelluric Data, Mid Valley, Nevada Test Site, Nevada.

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

Jackie M. Williams; Erin L. Wallin; Brian D. Rodriguez

2007-08-15

The United States Department of Energy (DOE) and the National Nuclear Security Administration (NNSA) at their Nevada Site Office (NSO) are addressing ground-water contamination resulting from historical underground nuclear testing through the Environmental Management (EM) program and, in particular, the Underground Test Area (UGTA) project. One issue of concern is the nature of the somewhat poorly constrained pre-Tertiary geology and its effects on ground-water flow. Ground-water modelers would like to know more about the hydrostratigraphy and geologic structure to support a hydrostratigraphic framework model that is under development for the Rainier Mesa/Shoshone Mountain Corrective Action Unit (CAU) (Bechtel Nevada, 2006).more » During 2003, the U.S. Geological Survey (USGS), in cooperation with the DOE and NNSA-NSO, collected and processed data at the Nevada Test Site in and near Yucca Flat (YF) to help define the character, thickness, and lateral extent of the pre-tertiary confining units. We collected 51 magnetotelluric (MT) and audio-magnetotelluric (AMT), stations for that research (Williams and others, 2005a, 2005b, 2005c, 2005d, 2005e, 2005f). In early 2005 we extended that research with 26 additional MT data stations (Williams and others, 2006), located on and near Rainier Mesa and Shoshone Mountain (RM-SM). The new stations extended the area of the hydrogeologic study previously conducted in Yucca Flat. This work was done to help refine what is known about the character, thickness, and lateral extent of pre-Tertiary confining units. In particular, a major goal was to define the upper clastic confining unit (UCCU). The UCCU is comprised of late Devonian to Mississippian siliciclastic rocks assigned to the Eleana Formation and Chainman Shale. The UCCU underlies the Yucca Flat area and extends westward towards Shoshone Mountain, southward to Buckboard Mesa, and northward to Rainier Mesa. Late in 2005 we collected another 14 MT stations in Mid Valley and in northern Yucca Flat basin. That work was done to better determine the extent and thickness of the UCCU near the southeastern RM-SM CAU boundary with the southwestern YF CAU, and also in the northern YF CAU. The purpose of this report is to release the MT data at those 14 stations shown in figure 1. No interpretation of the data is included here.« less

Integrated use of remotely sensed imagery and other data sets to infer the tectonics, structural style, and hydrocarbon habitats of the basins of the Tien Shan orogenic belt, Western China: A case study

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

Berry, J.L.; Nishidai, T.

1996-08-01

Remotely sensed imagery and various other published regional data sets (gravity, magnetics, earthquake data) were integrated in order to interpret the structural style, both at deep crustal levels and at the relatively shallow levels of interest to explorationists, of the Tien Shan. Cross-sections through the range were systematically prepared, and then palinspastically restored, constrained by the remote sensing interpretation, potential fields data, and published microplate movement vectors. Since large portions of the area are covered by late Tertiary orogenic sediments, the resulting interpretation focused on these areas, and what and how much geology lies concealed beneath them. We were ablemore » to demonstrate the likely consumption in the late Tertiary of over 100 km of Tarim Basin west along a broad front south of the Tien Shan, as well as within the Kuruktag area, where basins are compressional rather than extensional. There are also local areas of extension within the orogenic zone, and these can be explained using the known microplate boundaries, backward extrapolation of present microplate motions, and the type and extent of late Tertiary deformation within the plates as constraints. Relative and absolute microplate motions have to change greatly through Tertiary time in order to comply with these constraints. The results of this work allow one to infer the affinities, and hence something of the hydrocarbon potential, of fragmentary plates by reconstructing their motions. They also allow one to infer the nature of the stratigraphy, the likely depth of burial, and something of the maturation history of pre-Tertiary rocks buried by Tertiary sediments deposited in both compressional and extensional regimes.« less

Major structural controls on the distribution of pre-Tertiary rocks, Nevada Test Site vicinity, southern Nevada

USGS Publications Warehouse

Cole, James C.

1997-01-01

The lateral and vertical distributions of Proterozoic and Paleozoic sedimentary rocks in southern Nevada are the combined products of original stratigraphic relationships and post-depositional faults and folds. This map compilation shows the distribution of these pre-Tertiary rocks in the region including and surrounding the Nevada Test Site. It is based on considerable new evidence from detailed geologic mapping, biostratigraphic control, sedimentological analysis, and a review of regional map relationships.Proterozoic and Paleozoic rocks of the region record paleogeographic transitions between continental shelf depositional environments on the east and deeper-water slopefacies depositional environments on the west. Middle Devonian and Mississippian sequences, in particular, show strong lateral facies variations caused by contemporaneous changes in the western margin of North America during the Antler orogeny. Sections of rock that were originally deposited in widely separated facies localities presently lie in close proximity. These spatial relationships chiefly result from major east- and southeastdirected thrusts that deformed the region in Permian or later time.Somewhat younger contractional structures are identified within two irregular zones that traverse the region. These folds and thrusts typically verge toward the west and northwest and overprint the relatively simple pattern of the older contractional terranes. Local structural complications are significant near these younger structures due to the opposing vergence and due to irregularities in the previously folded and faulted crustal section.Structural and stratigraphic discontinuities are identified on opposing sides of two north-trending fault zones in the central part of the compilation region north of Yucca Flat. The origin and significance of these zones are enigmatic because they are largely covered by Tertiary and younger deposits. These faults most likely result from significant lateral offset, most likely in the sinistral sense.Low-angle normal faults that are at least older than Oligocene, and may pre-date Late Cretaceous time, are also present in the region. These faults are shown to locally displace blocks of pre-Tertiary rock by several kilometers. However, none of these structures can be traced for significant distances beyond its outcrop extent, and the inference is made that they do not exert regional influence on the distribution of pre-Tertiary rocks. The extensional strain accommodated by these low-angle normal faults appears to be local and highly irregular.

Solid-state NMR detection of 14N-13C dipolar couplings between amino acid side groups provides constraints on amyloid fibril architecture.

PubMed

Middleton, David A

2011-02-01

Solid-state nuclear magnetic resonance (SSNMR) is a powerful technique for the structural analysis of amyloid fibrils. With suitable isotope labelling patterns, SSNMR can provide constraints on the secondary structure, alignment and registration of β-strands within amyloid fibrils and identify the tertiary and quaternary contacts defining the packing of the β-sheet layers. Detection of (14)N-(13)C dipolar couplings may provide potentially useful additional structural constraints on β-sheet packing within amyloid fibrils but has not until now been exploited for this purpose. Here a frequency-selective, transfer of population in double resonance SSNMR experiment is used to detect a weak (14)N-(13)C dipolar coupling in amyloid-like fibrils of the peptide H(2)N-SNNFGAILSS-COOH, which was uniformly (13)C and (15)N labelled across the four C-terminal amino acids. The (14)N-(13)C interatomic distance between leucine and asparagine side groups is constrained between 2.4 and 3.8 Å, which allows current structural models of the β-spine arrangement within the fibrils to be refined. This procedure could be useful for the general structural analysis of other proteins in condensed phases and environments, such as biological membranes. Copyright © 2011 John Wiley & Sons, Ltd.

Distinctiveness of management in a university psychiatric hospital as a public health institution.

PubMed

Koncina, Miroslav

2008-06-01

The distinctiveness of management of a university psychiatric hospital which has the status of a public health institution is manifested in the following ways: * Distinctive features and characteristics of managing service provider organizations compared to those whose operational results involve tangible products; * Distinctive features of management which originate from its role as a regional hospital and a tertiary research and educational institution in the field of psychiatry, with special importance for the Republic of Slovenia as a whole; * Distinctive features of management that are defined by the social and legal framework of operation of public health institutions and their special social mission. This paper therefore discusses the specific theoretical and practical findings regarding management of service provider organizations from the viewpoint of their social mission and significance, as well as their legal organization, internal structure and values.

Vitrinite Reflectance Data for the Wind River Basin, Central Wyoming

USGS Publications Warehouse

Finn, Thomas M.; Roberts, Laura N.R.; Pawlewicz, Mark J.

2006-01-01

Introduction: The Wind River Basin is a large Laramide (Late Cretaceous through Eocene) structural and sedimentary basin that encompasses about 7,400 mi2 in central Wyoming. The basin boundaries are defined by fault-bounded Laramide uplifts that surround it, including the Owl Creek and Bighorn Mountains to the north, Wind River Range to the west, Granite Mountains to the south, and Casper Arch to the east. The purpose of this report is to present new vitrinite reflectance data to be used in support of the U.S Geological Survey assessment of undiscovered oil and gas resources of the Wind River Basin. One hundred and nineteen samples were collected from Jurassic through Tertiary rocks, mostly coal-bearing strata, in an effort to better understand and characterize the thermal maturation and burial history of potential source rocks.

Tectonic history of Sweetgrass Arch, Montana and Alberta-key to finding new hydrocarbons

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

Shepard, W. Shepard, B.

1985-05-01

The Sweetgrass arch of northwestern Montana and southern Alberta is a major ancient structural feature. Initial anticlinal emplacement occurred during the early Paleozoic and was parallel with the cratonic margin. Strong uplift followed by peneplanation occurred during the Late Jurassic and basal Cretaceous during the westward drifting of the North American plate following the breakup of Pangea. During Cretaceous and early Tertiary times, the Sweetgrass arch was quiescent, but was rejuvenated in mid to late Tertiary, upwarped by a basement flexure to its present structural configuration: a 200 mi (322 km) long, north-plunging anticline showing 10,000 ft (350 m) ofmore » structural relief. Midway down its plunge, the anticline is offset 30 mi (48 km) by a right-lateral transcurrent fault. During Late Cretaceous and early Tertiary, plutonic uplifts were emplaced on the east flank, forming traps for oil then migrating updip from the Williston and Alberta basins. Oil and gas accumulated in Mississippian, Jurassic, and basal Cretaceous reservoirs in structural and stratigraphic traps around these plutonic uplifts. Subsequent late Tertiary doming of the Sweetgrass arch tilted the earlier structural traps and drained them, resulting in remigration of much of the oil and gas to the crest of the arch. The tilting failed to destroy many of the stratigraphic traps. As a result, down the flanks of the Sweetgrass arch are many frozen stratigraphic traps including Cut Bank field, the largest single-pay stratigraphic trap in the north Rockies. On the crest are large structure accumulations of remigrated oil at Kevin Sunburst and Pondera. Evidence of remigration is recorded by live oil show tracks in the reservoirs and remnant gas caps throughout the area of earlier accumulations. A potential exists for finding new frozen traps on the flanks and remigrated oil accumulations on or near the crest of the Sweetgrass arch.« less

Geologic assessment of undiscovered oil and gas resources—Lower Cretaceous Albian to Upper Cretaceous Cenomanian carbonate rocks of the Fredericksburg and Washita Groups, United States Gulf of Mexico Coastal Plain and State Waters

USGS Publications Warehouse

Swanson, Sharon M.; Enomoto, Catherine B.; Dennen, Kristin O.; Valentine, Brett J.; Cahan, Steven M.

2017-02-10

In 2010, the U.S. Geological Survey (USGS) assessed Lower Cretaceous Albian to Upper Cretaceous Cenomanian carbonate rocks of the Fredericksburg and Washita Groups and their equivalent units for technically recoverable, undiscovered hydrocarbon resources underlying onshore lands and State Waters of the Gulf Coast region of the United States. This assessment was based on a geologic model that incorporates the Upper Jurassic-Cretaceous-Tertiary Composite Total Petroleum System (TPS) of the Gulf of Mexico basin; the TPS was defined previously by the USGS assessment team in the assessment of undiscovered hydrocarbon resources in Tertiary strata of the Gulf Coast region in 2007. One conventional assessment unit (AU), which extends from south Texas to the Florida panhandle, was defined: the Fredericksburg-Buda Carbonate Platform-Reef Gas and Oil AU. The assessed stratigraphic interval includes the Edwards Limestone of the Fredericksburg Group and the Georgetown and Buda Limestones of the Washita Group. The following factors were evaluated to define the AU and estimate oil and gas resources: potential source rocks, hydrocarbon migration, reservoir porosity and permeability, traps and seals, structural features, paleoenvironments (back-reef lagoon, reef, and fore-reef environments), and the potential for water washing of hydrocarbons near outcrop areas.In Texas and Louisiana, the downdip boundary of the AU was defined as a line that extends 10 miles downdip of the Lower Cretaceous shelf margin to include potential reef-talus hydrocarbon reservoirs. In Mississippi, Alabama, and the panhandle area of Florida, where the Lower Cretaceous shelf margin extends offshore, the downdip boundary was defined by the offshore boundary of State Waters. Updip boundaries of the AU were drawn based on the updip extent of carbonate rocks within the assessed interval, the presence of basin-margin fault zones, and the presence of producing wells. Other factors evaluated were the middle Cenomanian sea-level fall and erosion that removed large portions of platform and platform-margin carbonate sediments in the Washita Group of central Louisiana. The production history of discovered reservoirs and well data within the AU were examined to estimate the number and size of undiscovered oil and gas reservoirs within the AU. Using the USGS National Oil and Gas Assessment resource assessment methodology, mean volumes of 40 million barrels of oil, 622 billion cubic feet of gas, and 14 million barrels of natural gas liquids are the estimated technically recoverable undiscovered resources for the Fredericksburg-Buda Carbonate Platform-Reef Gas and Oil AU.

About Student's Media Use for Learning in Tertiary Education Influence Factors and Structures of Usage Behavior

ERIC Educational Resources Information Center

Grosch, Michael

2014-01-01

The rise of the web 2.0 led to dramatic changes in media usage behavior of students in tertiary education. Services such as Google and Facebook are most accepted amongst students not only in pastime but also for learning. A representative survey was made at Karlsruhe Institute of Technology (KIT). About 1,400 students were asked 150 questions to…

Genetic diversity, genetic structure, and mating system of brewer spruce (Pinaceae), a relict of the acto-tertiary forest

Treesearch

F. Thomas Ledig; Paul D. Hodgskiss; David R. Johnson

2005-01-01

Brewer spruce (Picea breweriana), a relict of the widespread Arcto-Tertiary forests, is now restricted to a highly fragmented range in the Klamath Region of California and Oregon. Expected heterozygosity for 26 isozyme loci, averaged over 10 populations, was 0.121. More notable than the relatively high level of diversity when compared to other woody...

Lithospheric mantle structure beneath Northern Scotland: Pre-plume remnant or syn-plume signature?

NASA Astrophysics Data System (ADS)

Knapp, J.

2003-04-01

Upper mantle reflectors (Flannan and W) beneath the northwestern British Isles are some of the best-known and most-studied examples of preserved structure within the continental mantle lithosphere, and are spatially coincident with the surface location of early Iceland plume volcanism in the British Tertiary Province. First observed on BIRPS (British Institutions Reflection Profiling Syndicate) marine deep seismic reflection profiles in the early 1980's, these reflectors have subsequently been imaged and correlated on additional reflection and refraction profiles in the offshore area of northern and western Scotland. The age and tectonic significance of these reflectors remains a subject of wide debate, due in part to the absence of robust characterization of the upper mantle velocity structure in this tectonically complex area. Interpretations advanced over the past two decades for the dipping Flannan reflector range from fossilized subduction complex to large-scale extensional shear zone, and span ages from Proterozoic to early Mesozoic. Crustal geology of the region records early Paleozoic continental collision and late Paleozoic to Mesozoic extension. Significant modification of the British lithosphere in early Tertiary time, including dramatic thinning and extensive basaltic intrusion associated with initiation and development of the Iceland plume, suggests either (1) an early Tertiary age for the Flannan reflector or (2) preservation of ancient features within the mantle lithosphere despite such pervasive modification. Exisitng constraints are consistent with a model for early Tertiary origin of the Flannan reflector as the downdip continuation of the Rockall Trough extensional system of latest Cretaceous to earliest Tertiary age during opening of the northern Atlantic Ocean and initiation of the Iceland plume. Lithopsheric thinning beneath present-day northern Scotland could have served to focus the early expression of plume volcanism (British Tertiary Province), despite the inferred distant locus of the initial plume head. Alternatively, preservation of large-scale pre-plume fabric in the Scottish mantle would imply long-lived tectonic heredity in the continental lithospheric mantle, and place important constraints on the plume-related effects (or lack thereof) in the mantle lithosphere.

Disaster resilience in tertiary hospitals: a cross-sectional survey in Shandong Province, China

PubMed Central

2014-01-01

Background Hospital disaster resilience can be defined as a hospital’s ability to resist, absorb, and respond to the shock of disasters while maintaining critical functions, and then to recover to its original state or adapt to a new one. This study aims to explore the status of resilience among tertiary hospitals in Shandong Province, China. Methods A stratified random sample (n = 50) was derived from tertiary A, tertiary B, and tertiary C hospitals in Shandong Province, and was surveyed by questionnaire. Data on hospital characteristics and 8 key domains of hospital resilience were collected and analysed. Variables were binary, and analysed using descriptive statistics such as frequencies. Results A response rate of 82% (n = 41) was attained. Factor analysis identified four key factors from eight domains which appear to reflect the overall level of disaster resilience. These were hospital safety, disaster management mechanisms, disaster resources and disaster medical care capability. The survey demonstrated that in regard to hospital safety, 93% had syndromic surveillance systems for infectious diseases and 68% had evaluated their safety standards. In regard to disaster management mechanisms, all had general plans, while only 20% had specific plans for individual hazards. 49% had a public communication protocol and 43.9% attended the local coordination meetings. In regard to disaster resources, 75.6% and 87.5% stockpiled emergency drugs and materials respectively, while less than a third (30%) had a signed Memorandum of Understanding with other hospitals to share these resources. Finally in regard to medical care, 66% could dispatch an on-site medical rescue team, but only 5% had a ‘portable hospital’ function and 36.6% and 12% of the hospitals could surge their beds and staff capacity respectively. The average beds surge capacity within 1 day was 13%. Conclusions This study validated the broad utility of a framework for understanding and measuring the level of hospital resilience. The survey demonstrated considerable variability in disaster resilience arrangements of tertiary hospitals in Shandong province, and the difference between tertiary A hospitals and tertiary B hospitals was also identified in essential areas. PMID:24661641

Disaster resilience in tertiary hospitals: a cross-sectional survey in Shandong Province, China.

PubMed

Zhong, Shuang; Hou, Xiang-Yu; Clark, Michele; Zang, Yu-Li; Wang, Lu; Xu, Ling-Zhong; FitzGerald, Gerard

2014-03-25

Hospital disaster resilience can be defined as a hospital's ability to resist, absorb, and respond to the shock of disasters while maintaining critical functions, and then to recover to its original state or adapt to a new one. This study aims to explore the status of resilience among tertiary hospitals in Shandong Province, China. A stratified random sample (n = 50) was derived from tertiary A, tertiary B, and tertiary C hospitals in Shandong Province, and was surveyed by questionnaire. Data on hospital characteristics and 8 key domains of hospital resilience were collected and analysed. Variables were binary, and analysed using descriptive statistics such as frequencies. A response rate of 82% (n = 41) was attained. Factor analysis identified four key factors from eight domains which appear to reflect the overall level of disaster resilience. These were hospital safety, disaster management mechanisms, disaster resources and disaster medical care capability. The survey demonstrated that in regard to hospital safety, 93% had syndromic surveillance systems for infectious diseases and 68% had evaluated their safety standards. In regard to disaster management mechanisms, all had general plans, while only 20% had specific plans for individual hazards. 49% had a public communication protocol and 43.9% attended the local coordination meetings. In regard to disaster resources, 75.6% and 87.5% stockpiled emergency drugs and materials respectively, while less than a third (30%) had a signed Memorandum of Understanding with other hospitals to share these resources. Finally in regard to medical care, 66% could dispatch an on-site medical rescue team, but only 5% had a 'portable hospital' function and 36.6% and 12% of the hospitals could surge their beds and staff capacity respectively. The average beds surge capacity within 1 day was 13%. This study validated the broad utility of a framework for understanding and measuring the level of hospital resilience. The survey demonstrated considerable variability in disaster resilience arrangements of tertiary hospitals in Shandong province, and the difference between tertiary A hospitals and tertiary B hospitals was also identified in essential areas.

Tertiary-amine-containing thermo- and pH-sensitive hydrophilic ABA triblock copolymers: effect of different tertiary amines on thermally induced sol-gel transitions.

PubMed

Henn, Daniel M; Wright, Roger A E; Woodcock, Jeremiah W; Hu, Bin; Zhao, Bin

2014-03-11

This Article reports on the synthesis of a series of well-defined, tertiary-amine-containing ABA triblock copolymers, composed of a poly(ethylene oxide) (PEO) central block and thermo- and pH-sensitive outer blocks, and the study of the effect of different tertiary amines on thermally induced sol-gel transition temperatures (T(sol-gel)) of their 10 wt % aqueous solutions. The doubly responsive ABA triblock copolymers were prepared from a difunctional PEO macroinitiator by atom transfer radical polymerization of methoxydi(ethylene glycol) methacrylate and ethoxydi(ethylene glycol) methacrylate at a feed molar ratio of 30:70 with ∼5 mol % of either N,N-diethylaminoethyl methacrylate (DEAEMA), N,N-diisopropylaminoethyl methacrylate, or N,N-di(n-butyl)aminoethyl methacrylate. The chain lengths of thermosensitive outer blocks and the molar contents of tertiary amines were very similar for all copolymers. Using rheological measurements, we determined the pH dependences of T(sol-gel) of 10 wt % aqueous solutions of these copolymers in a phosphate buffer. The T(sol-gel) versus pH curves of all polymers exhibited a sigmoidal shape. The T(sol-gel) increased with decreasing pH; the changes were small on both high and low pH sides. At a specific pH, the T(sol-gel) decreased with increasing the hydrophobicity of the tertiary amine, and upon decreasing pH the onset pH value for the T(sol-gel) to begin to increase noticeably was lower for the more hydrophobic tertiary amine-containing copolymer. In addition, we studied the effect of different tertiary amines on the release behavior of FITC-dextran from 10 wt % micellar gels in an acidic medium at 37 and 27 °C. The release profiles for three studied hydrogels at 37 °C were essentially the same, suggesting that the release was dominated by the diffusion of FITC-dextran. At 27 °C, the release was significantly faster for the DEAEMA-containing copolymer, indicating that both diffusion and gel dissolution contributed to the release at this temperature.

Algeria: structural evolution and hydrocarbon potential of a complicated Tectonic province

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

Knudsen, H.W.

1985-02-01

During most of the pre-Carboniferous, Algeria was part of a stable foreland platform on which a thick clastic sequence was deposited. Caledonian tectonics were primarily epeirogenic, but they established structural alignments that were further reinforced by the much stronger movements of the Carboniferous Hercynian orogeny. In northern and eastern Algeria, a variable basal sandstone and a thick sequence of Triassic and Lower Jurassic evaporites were deposited over the eroded Hercynian surface. This provided a seal for subsequent hydrocarbon migration from the underlying Silurian and Devonian source rocks. Important epeirogenic events and tensional faulting occurred during the Jurassic and Cretaceous. Compressionalmore » forces in the tertiary culminated in the Alpine orogeny. A broad zone of uplift and southward-directed imbricate thrusting formed along the northern margins of Algeria obscuring much of the sub-Tertiary depositional and structural features. Hydrocarbon accumulation in Algeria has been predominantly controlled by the relationships among the Silurian-Devonian source rocks, the Hercynian unconformity, and the distribution of the overlying Triassic clastic and evaporite sequence. More than 65% of the recoverable oil reserves and 90% of the gas reserves are trapped immediately below or above the Hercynian unconformity, with the evaporites providing the seal. Heretofore, the complex geology of the Tertiary overthrust zone has been a deterrent to exploration in both the autochthonous Miocene basins and the sub-Tertiary sequence. However, improved seismic techniques and renewed interest in the potential of overthrust provinces point to increased activity in this area.« less

The tolerance to exchanges of the Watson–Crick base pair in the hammerhead ribozyme core is determined by surrounding elements

PubMed Central

Przybilski, Rita; Hammann, Christian

2007-01-01

Tertiary interacting elements are important features of functional RNA molecules, for example, in all small nucleolytic ribozymes. The recent crystal structure of a tertiary stabilized type I hammerhead ribozyme revealed a conventional Watson–Crick base pair in the catalytic core, formed between nucleotides C3 and G8. We show that any Watson–Crick base pair between these positions retains cleavage competence in two type III ribozymes. In the Arabidopsis thaliana sequence, only moderate differences in cleavage rates are observed for the different base pairs, while the peach latent mosaic viroid (PLMVd) ribozyme exhibits a preference for a pyrimidine at position 3 and a purine at position 8. To understand these differences, we created a series of chimeric ribozymes in which we swapped sequence elements that surround the catalytic core. The kinetic characterization of the resulting ribozymes revealed that the tertiary interacting loop sequences of the PLMVd ribozyme are sufficient to induce the preference for Y3–R8 base pairs in the A. thaliana hammerhead ribozyme. In contrast to this, only when the entire stem–loops I and II of the A. thaliana sequences are grafted on the PLMVd ribozyme is any Watson–Crick base pair similarly tolerated. The data provide evidence for a complex interplay of secondary and tertiary structure elements that lead, mediated by long-range effects, to an individual modulation of the local structure in the catalytic core of different hammerhead ribozymes. PMID:17666711

Hyperactive gp130/STAT3‐driven gastric tumourigenesis promotes submucosal tertiary lymphoid structure development

PubMed Central

Hill, David G.; Yu, Liang; Gao, Hugh; Balic, Jesse J.; West, Alison; Oshima, Hiroko; McLeod, Louise; Oshima, Masanobu; Gallimore, Awen; D'Costa, Kimberley; Bhathal, Prithi S.; Sievert, William; Ferrero, Richard L.

2018-01-01

Tertiary lymphoid structures (TLSs) display phenotypic and functional characteristics of secondary lymphoid organs, and often develop in tissues affected by chronic inflammation, as well as in certain inflammation‐associated cancers where they are prognostic of improved patient survival. However, the mechanisms that govern the development of tumour‐associated TLSs remain ill‐defined. Here, we observed tumour‐associated TLSs in a preclinical mouse model (gp130 F/F) of gastric cancer, where tumourigenesis is dependent on hyperactive STAT3 signalling through the common IL‐6 family signalling receptor, gp130. Gastric tumourigenesis was associated with the development of B and T cell‐rich submucosal lymphoid aggregates, containing CD21+ cellular networks and high endothelial venules. Temporally, TLS formation coincided with the development of gastric adenomas and induction of homeostatic chemokines including Cxcl13, Ccl19 and Ccl21. Reflecting the requirement of gp130‐driven STAT3 signalling for gastric tumourigenesis, submucosal TLS development was also STAT3‐dependent, but independent of the cytokine IL‐17 which has been linked with lymphoid neogenesis in chronic inflammation and autoimmunity. Interestingly, upregulated lymphoid chemokine expression and TLS formation were also observed in a chronic gastritis model induced by Helicobacter felis infection. Tumour‐associated TLSs were also observed in patients with intestinal‐type gastric cancer, and a gene signature linked with TLS development in gp130 F/F mice was associated with advanced clinical disease, but was not prognostic of patient survival. Collectively, our in vivo data reveal that hyperactive gp130‐STAT3 signalling closely links gastric tumourigenesis with lymphoid neogenesis, and while a TLS gene signature was associated with advanced gastric cancer in patients, it did not indicate a favourable prognosis. PMID:29417587

Independent Structural Domains in Paramyxovirus Polymerase Protein*

PubMed Central

Dochow, Melanie; Krumm, Stefanie A.; Crowe, James E.; Moore, Martin L.; Plemper, Richard K.

2012-01-01

All enzymatic activities required for genomic replication and transcription of nonsegmented negative strand RNA viruses (or Mononegavirales) are believed to be concentrated in the viral polymerase (L) protein. However, our insight into the organization of these different enzymatic activities into a bioactive tertiary structure remains rudimentary. Fragments of Mononegavirales polymerases analyzed to date cannot restore bioactivity through trans-complementation, unlike the related L proteins of segmented NSVs. We investigated the domain organization of phylogenetically diverse Paramyxovirus L proteins derived from measles virus (MeV), Nipah virus (NiV), and respiratory syncytial virus (RSV). Through a comprehensive in silico and experimental analysis of domain intersections, we defined MeV L position 615 as an interdomain candidate in addition to the previously reported residue 1708. Only position 1708 of MeV and the homologous positions in NiV and RSV L also tolerated the insertion of epitope tags. Splitting of MeV L at residue 1708 created fragments that were unable to physically interact and trans-complement, but strikingly, these activities were reconstituted by the addition of dimerization tags to the fragments. Equivalently split fragments of NiV, RSV, and MeV L oligomerized with comparable efficiency in all homo- and heterotypic combinations, but only the homotypic pairs were able to trans-complement. These results demonstrate that synthesis as a single polypeptide is not required for the Mononegavirales polymerases to adopt a proper tertiary conformation. Paramyxovirus polymerases are composed of at least two truly independent folding domains that lack a traditional interface but require molecular compatibility for bioactivity. The functional probing of the L domain architecture through trans-complementation is anticipated to be applicable to all Mononegavirales polymerases. PMID:22215662

Helix A Stabilization Precedes Amino-terminal Lobe Activation upon Calcium Binding to Calmodulin

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

Chen, Baowei; Lowry, David; Mayer, M. Uljana

2008-08-09

The structural coupling between opposing domains of CaM was investigated using the conformationally sensitive biarsenical probe 4,5-bis(1,3,2-dithioarsolan-2-yl)-resorufin (ReAsH), which upon binding to an engineered tetracysteine binding motif near the end of helix A (Thr-5 to Phe-19) becomes highly fluorescent. Changes in conformation and dynamics are reflective of the native CaM structure, as there is no change in the 1H- 15N HSQC NMR spectrum in comparison to wild-type CaM. We find evidence of a conformational intermediate associated with CaM activation, where calcium occupancy of sites in the amino-terminal and carboxyl-terminal lobes of CaM differentially affect the fluorescence intensity of bound ReAsH.more » Insight into the structure of the conformational intermediate is possible from a consideration of calcium-dependent changes in rates of ReAsH binding and helix A mobility, which respectively distinguish secondary structural changes associated with helix A stabilization from the tertiary structural reorganization of the amino-terminal lobe of CaM necessary for high-affinity binding to target proteins. Helix A stabilization is associated with calcium occupancy of sites in the carboxyl-terminal lobe (Kd = 0.36 ± 0.04 μM), which results in a reduction in the rate of ReAsH binding from 4900 M -1 sec -1 to 370 M -1 sec -1. In comparison, tertiary structural changes involving helix A and other structural elements in the amino-terminal lobe requires calcium-occupancy of amino-terminal sites (Kd = 18 ± 3 μM). Observed secondary and tertiary structural changes involving helix A in response to the sequential calcium occupancy of carboxyl- and amino-terminal lobe calcium binding sites suggest an important involvement of helix A in mediating the structural coupling between the opposing domains of CaM. These results are discussed in terms of a model in which carboxyl-terminal lobe calcium activation induces secondary structural changes within the interdomain linker that release helix A, thereby facilitating the formation of calcium binding sites in the amino-terminal lobe and linked tertiary structural rearrangements to form a high-affinity binding cleft that can associate with target proteins.« less

Molecular surface representation using 3D Zernike descriptors for protein shape comparison and docking.

PubMed

Kihara, Daisuke; Sael, Lee; Chikhi, Rayan; Esquivel-Rodriguez, Juan

2011-09-01

The tertiary structures of proteins have been solved in an increasing pace in recent years. To capitalize the enormous efforts paid for accumulating the structure data, efficient and effective computational methods need to be developed for comparing, searching, and investigating interactions of protein structures. We introduce the 3D Zernike descriptor (3DZD), an emerging technique to describe molecular surfaces. The 3DZD is a series expansion of mathematical three-dimensional function, and thus a tertiary structure is represented compactly by a vector of coefficients of terms in the series. A strong advantage of the 3DZD is that it is invariant to rotation of target object to be represented. These two characteristics of the 3DZD allow rapid comparison of surface shapes, which is sufficient for real-time structure database screening. In this article, we review various applications of the 3DZD, which have been recently proposed.

Effects of topographic position and geology on shaking damage to residential wood-framed structures during the 2003 San Simeon earthquake, western San Luis obispo county, California

USGS Publications Warehouse

McCrink, T.P.; Wills, C.J.; Real, C.R.; Manson, M.W.

2010-01-01

A statistical evaluation of shaking damage to wood-framed houses caused by the 2003 M6.5 San Simeon earthquake indicates that both the rate and severity of damage, independent of structure type, are significantly greater on hilltops compared to hill slopes when underlain by Cretaceous or Tertiary sedimentary rocks. This increase in damage is interpreted to be the result of topographic amplification. An increase in the damage rate is found for all structures built on Plio-Pleistocene rocks independent of topographic position, and this is interpreted to be the result of amplified shaking caused by geologic site response. Damage rate and severity to houses built on Tertiary rocks suggest that amplification due to both topographic position and geologic site response may be occurring in these rocks, but effects from other topographic parameters cannot be ruled out. For all geologic and topographic conditions, houses with raised foundations are more frequently damaged than those with slab foundations. However, the severity of damage to houses on raised foundations is only significantly greater for those on hill slopes underlain by Tertiary rocks. Structures with some damage-resistant characteristics experienced greater damage severity on hilltops, suggesting a spectral response to topographic amplification. ?? 2010, Earthquake Engineering Research Institute.

Clients, Colleagues or Experts? Defining Identities in an Action Research Project

ERIC Educational Resources Information Center

Coco, Angela; Varnier, Catherine; Deftereos, Chris

2007-01-01

This article examines how discourses shaped and were shaped by participants' identities in a participatory action research (PAR) project in a tertiary education environment. The primary researcher and the director of the university's desktop publishing team explored the idea of working together to help the newly formed team to develop strategies…

A new Cretaceous-Tertiary boundary locality in the western powder River basin, Wyoming: biological and geological implications

USGS Publications Warehouse

Nichols, D.J.; Brown, J.L.; Attrep, M.; Orth, C.J.

1992-01-01

A newly discovered Cretaceous-Tertiary (K-T) boundary locality in the western Powder River basin, Wyoming, is characterized by a palynologically defined extinction horizon, a fern-spore abundance anomaly, a strong iridium anomaly, and shock-metamorphosed quartz grains. Detailed microstratigraphic analyses show that about one third of the palynoflora (mostly angiosperm pollen) disappeared abruptly, placing the K-T boundary within a distinctive, 1- to 2-cm-thick claystone layer. Shocked quartz grains are concentrated at the top of this layer, and although fern-spore and iridium concentrations are high in this layer, they reach their maximum concentrations in a 2-cm-thick carbonaceous claystone that overlies the boundary claystone layer. The evidence supports the theory that the K-T boundary event was associated with the impact of an extraterrestrial body or bodies. Palynological analyses of samples from the K-T boundary interval document extensive changes in the flora that resulted from the boundary event. The palynologically and geochemically defined K-T boundary provides a unique time-line of use in regional basin analysis. ?? 1992.

Mineralogy of Cretaceous/Tertiary boundary clays in the Chicxulub structure in northern Yucatan

NASA Technical Reports Server (NTRS)

Ming, D. W.; Sharpton, Virgil L.; Schuraytz, B. C.

1991-01-01

The Cretaceous/Tertiary (K/T) boundary clay layer is thought to be derived from ejecta material from meteorite impact, based on the anomalous concentrations of noble metals in the layer. Because of recent findings of a half-meter thick ejecta deposit at the K/T boundary in Haiti, efforts have focused on locating a large impact feature in the Caribbean and the Gulf of Mexico. One of the leading candidates for the site of a large impact is the Chicxulub structure located on the northern Yucatan Peninsula in Mexico. The Chicxulub structure is a subsurface zone of upper Cretaceous igneous rocks, carbonates, and breccias. The structure has been interpreted to be a 200 km diameter; however, there is some question to the size of the structure or to the fact that it even is an impact feature. Little is known about the mineralogy of this structure; the objective of this study was to determine the clay mineralogy of core samples from within the Chicxulub structure.

Both Reversible Self-Association and Structural Changes Underpin Molecular Viscoelasticity of mAb Solutions.

PubMed

Sarangapani, Prasad S; Weaver, Justin; Parupudi, Arun; Besong, Tabot M D; Adams, Gary G; Harding, Stephen E; Manikwar, Prakash; Castellanos, Maria M; Bishop, Steven M; Pathak, Jai A

2016-12-01

The role of antibody structure (conformation) in solution rheology is probed. It is demonstrated here that pH-dependent changes in the tertiary structure of 2 mAb solutions lead to viscoelasticity and not merely a shear viscosity (η) increase. Steady shear flow curves on mAb solutions are reported over broad pH (3.0 ≤ pH ≤ 8.7) and concentration (2 mg/mL ≤ c ≤ 120 mg/mL) ranges to comprehensively characterize their rheology. Results are interpreted using size exclusion chromatography, differential scanning calorimetry, analytical ultracentrifugation, near-UV circular dichroism, and dynamic light scattering. Changes in tertiary structure with concentration lead to elastic yield stress and increased solution viscosity in solution of "mAb1." These findings are supported by dynamic light scattering and differential scanning calorimetry, which show increased hydrodynamic radius of mAb1 at low pH and a reduced melting temperature T m , respectively. Conversely, another molecule at 120 mg/mL solution concentration is a strong viscoelastic gel due to perturbed tertiary structure (seen in circular dichroism) at pH 3.0, but the same molecule responds as a viscous liquid due to reversible self-association at pH 7.4 (verified by analytical ultracentrifugation). Both protein-protein interactions and structural perturbations govern pH-dependent viscoelasticity of mAb solutions. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Superacid synthesized tertiary benzenesulfonamides and benzofuzed sultams act as selective hCA IX inhibitors: toward understanding a new mode of inhibition by tertiary sulfonamides.

PubMed

Métayer, Benoît; Martin-Mingot, Agnès; Vullo, Daniella; Supuran, Claudiu T; Thibaudeau, Sébastien

2013-11-21

A series of tertiary (fluorinated) benzenesulfonamides was synthesized in superacid HF-SbF5. To circumvent the problem of the in situ iminium ion formation, proved by low temperature NMR experiments, a tandem superacid catalysed cross-coupling reaction was employed to synthesize the benzofuzed sultams analogues. These tertiary benzenesulfonamides were tested as inhibitors of human carbonic anhydrases (hCAs, EC 4.2.1.1). These compounds did not inhibit the widespread off target hCA II isoform and showed strong selectivity toward tumor-associated carbonic anhydrase isoform IX. A dramatic effect of the electronic and structural shape of the inhibitors on selectivity was demonstrated, confirming the non-zinc-bonding mode of inhibition of this class of sulfonamides. This work allowed identifying a highly selective hCA IX inhibitor lead in this series.

A Case Series of the Probability Density and Cumulative Distribution of Laryngeal Disease in a Tertiary Care Voice Center.

PubMed

de la Fuente, Jaime; Garrett, C Gaelyn; Ossoff, Robert; Vinson, Kim; Francis, David O; Gelbard, Alexander

2017-11-01

To examine the distribution of clinic and operative pathology in a tertiary care laryngology practice. Probability density and cumulative distribution analyses (Pareto analysis) was used to rank order laryngeal conditions seen in an outpatient tertiary care laryngology practice and those requiring surgical intervention during a 3-year period. Among 3783 new clinic consultations and 1380 operative procedures, voice disorders were the most common primary diagnostic category seen in clinic (n = 3223), followed by airway (n = 374) and swallowing (n = 186) disorders. Within the voice strata, the most common primary ICD-9 code used was dysphonia (41%), followed by unilateral vocal fold paralysis (UVFP) (9%) and cough (7%). Among new voice patients, 45% were found to have a structural abnormality. The most common surgical indications were laryngotracheal stenosis (37%), followed by recurrent respiratory papillomatosis (18%) and UVFP (17%). Nearly 55% of patients presenting to a tertiary referral laryngology practice did not have an identifiable structural abnormality in the larynx on direct or indirect examination. The distribution of ICD-9 codes requiring surgical intervention was disparate from that seen in clinic. Application of the Pareto principle may improve resource allocation in laryngology, but these initial results require confirmation across multiple institutions.

Rhodamine Inhibitors of P-glycoprotein: An Amide/Thioamide “Switch” for ATPase Activity

PubMed Central

Gannon, Michael K.; Holt, Jason J.; Bennett, Stephanie M.; Wetzel, Bryan R.; Loo, Tip W.; Bartlett, M. Claire; Clarke, David M.; Sawada, Geri A.; Higgins, J. William; Tombline, Gregory; Raub, Thomas J.; Detty, Michael R.

2012-01-01

We have examined 46 tetramethylrosamine/rhodamine derivatives with structural diversity in the heteroatom of the xanthylium core, the amino substituents of the 3- and 6-positions, and the alkyl, aryl, or heteroaryl group at the 9-substituent. These compounds were examined for affinity and ATPase stimulation in isolated MDR3 CL P-gp and human P-gp-His10, for their ability to promote uptake of calcein AM and vinblastine in multidrug-resistant MDCKII-MDR1 cells, and for transport in monolayers of MDCKII-MDR1 cells. Thioamide 31-S gave KM of 0.087 μM in human P-gp. Small changes in structure among this set of compounds affected affinity as well as transport rate (or flux) even though all derivatives examined were substrates for P-gp. With isolated protein, tertiary amide groups dictate high affinity and high stimulation while tertiary thioamide groups give high affinity and inhibition of ATPase activity. In MDCKII-MDR1 cells, the tertiary thioamide-containing derivatives promote uptake of calcein AM and have very slow passive, absorptive, and secretory rates of transport relative to transport rates for tertiary amide-containing derivatives. Thioamide 31-S promoted uptake of calcein AM and inhibited efflux of vinblastine with IC50’s of ~2 μM in MDCKII-MDR1 cells. PMID:19402665

Nanosecond Absorption Spectroscopy of Hemoglobin: Elementary Processes in Kinetic Cooperativity

NASA Astrophysics Data System (ADS)

Hofrichter, James; Sommer, Joseph H.; Henry, Eric R.; Eaton, William A.

1983-04-01

A nanosecond absorption spectrometer has been used to measure the optical spectra of hemoglobin between 3 ns and 100 ms after photolysis of the CO complex. The data from a single experiment comprise a surface, defined by the time-ordered set of 50-100 spectra. Singular value decomposition is used to represent the observed spectra in terms of a minimal set of basis spectra and the time course of their amplitudes. Both CO rebinding and conformational changes are found to be multiphasic. Prior to the quaternary structural change, two relaxations are observed that are assigned to geminate recombination followed by a tertiary structural change. These relaxations are interpreted in terms of a kinetic model that points out their potential role in kinetic cooperativity. The rapid escape of CO from the heme pocket compared with the rate of rebinding observed for both R and T quaternary states shows that the quaternary structure controls the overall dissociation rate by changing the rate at which the Fe--CO bond is broken. A comparable description of the control of the overall association rates must await a more complete experimental description of the kinetics of the quaternary T state.

The effects of health education on knowledge and attitudes to emergency contraception by female students of a tertiary educational institution in Enugu, South East Nigeria.

PubMed

Arinze-Onyia, S U; Onwasigwe, C N; Uzochukwu, B S C; Nwobi, E A; Ndu, A C; Nwobodo, Ed

2010-11-28

This was an intervention study to assess the effects of health education on the knowledge and attitudes to emergency contraception (EC) by female students of University of Nigeria in southeast Nigeria. A structured questionnaire was used to collect data from 337 female students of a tertiary educational institution (150 in the study group and 187 from the control group) who were selected by multistage sampling. Subsequently, health education was conducted only among students in the study institution. Three months after this intervention, its effects were assessed through a survey using the same structured questionnaire employed in the baseline survey. Unlike the pre-intervention results, knowledge of EC was significantly higher among the study group than the controls. Attitudes to EC were also more favourable at the post- intervention survey among the study group. Health education can effectively improve knowledge and attitudes to EC among female students of tertiary institutions and this should be encouraged.

Tertiary tilting and dismemberment of the laramide arc and related hydrothermal systems, Sierrita Mountain, Arizona

USGS Publications Warehouse

Stavast, W.J.A.; Butler, R.P.; Seedorff, E.; Barton, M.D.; Ferguson, C.A.

2008-01-01

Multiple lines of evidence, including new and published geologic mapping and paleomagnetic and geobarometric determinations, demonstrate that the rocks and large porphyry copper systems of the Sierrita Mountains in southern Arizona were dismembered and tilted 50?? to 60?? to the south by Tertiary normal faulting. Repetition of geologic features and geobarometry indicate that the area is segmented into at least three major structural blocks, and the present surface corresponds to oblique sections through the Laramide plutonic-hydrothermal complex, ranging in paleodepth from ???1 to ???12 km. These results add to an evolving view of a north-south extensional domain at high angles to much extension in the southern Basin and Range, contrast with earlier interpretations that the Laramide systems are largely upright and dismembered by thrust faults, highlight the necessity of restoring Tertiary rotations before interpreting Laramide structural and hydrothermal features, and add to the broader understanding of pluton emplacement and evolution of porphyry copper systems. ?? 2008 Society of Economic Geologists, Inc.

Optical spectroscopic methods for probing the conformational stability of immobilised enzymes.

PubMed

Ganesan, Ashok; Moore, Barry D; Kelly, Sharon M; Price, Nicholas C; Rolinski, Olaf J; Birch, David J S; Dunkin, Ian R; Halling, Peter J

2009-07-13

We report the development of biophysical techniques based on circular dichroism (CD), diffuse reflectance infrared Fourier transform (DRIFT) and tryptophan (Trp) fluorescence to investigate in situ the structure of enzymes immobilised on solid particles. Their applicability is demonstrated using subtilisin Carlsberg (SC) immobilised on silica gel and Candida antartica lipase B immobilised on Lewatit VP.OC 1600 (Novozyme 435). SC shows nearly identical secondary structure in solution and in the immobilised state as evident from far UV CD spectra and amide I vibration bands. Increased near UV CD intensity and reduced Trp fluorescence suggest a more rigid tertiary structure on the silica surface. After immobilised SC is inactivated, these techniques reveal: a) almost complete loss of near UV CD signal, suggesting loss of tertiary structure; b) a shift in the amide I vibrational band from 1658 cm(-1) to 1632 cm(-1), indicating a shift from alpha-helical structure to beta-sheet; c) a substantial blue shift and reduced dichroism in the far UV CD, supporting a shift to beta-sheet structure; d) strong increase in Trp fluorescence intensity, which reflects reduced intramolecular quenching with loss of tertiary structure; and e) major change in fluorescence lifetime distribution, confirming a substantial change in Trp environment. DRIFT measurements suggest that pressing KBr discs may perturb protein structure. With the enzyme on organic polymer it was possible to obtain near UV CD spectra free of interference by the carrier material. However, far UV CD, DRIFT and fluorescence measurements showed strong signals from the organic support. In conclusion, the spectroscopic methods described here provide structural information hitherto inaccessible, with their applicability limited by interference from, rather than the particulate nature of, the support material.

Structural specificity of Rn nuclease I as probed on yeast tRNA(Phe) and tRNA(Asp).

PubMed Central

Przykorska, A; el Adlouni, C; Keith, G; Szarkowski, J W; Dirheimer, G

1992-01-01

A single-strand-specific nuclease from rye germ (Rn nuclease I) was characterized as a tool for secondary and tertiary structure investigation of RNAs. To test the procedure, yeast tRNA(Phe) and tRNA(Asp) for which the tertiary structures are known, as well as the 3'-half of tRNA(Asp) were used as substrates. In tRNA(Phe) the nuclease introduced main primary cuts at positions U33 and A35 of the anticodon loop and G18 and G19 of the D loop. No primary cuts were observed within the double stranded stems. In tRNA(Asp) the main cuts occurred at positions U33, G34, U35, C36 of the anticodon loop and G18 and C20:1 positions in the D loop. No cuts were observed in the T loop in intact tRNA(Asp) but strong primary cleavages occurred at positions psi 55, C56, A57 within that loop in the absence of the tertiary interactions between T and D loops (use of 3'-half tRNA(Asp)). These results show that Rn nuclease I is specific for exposed single-stranded regions. Images PMID:1542562

Geologic Map of the Gold Creek Gold District, Elko County, Nevada

USGS Publications Warehouse

Ketner, Keith B.

2007-01-01

The Gold Creek, Nev. area displays important stratigraphic and structural relationships between Paleozoic and early Tertiary sedimentary strata in an area dominated by large intrusive bodies of Mesozoic age and extensive volcanic fields of middle to late Tertiary age. An autochthonous sequence includes the Cambrian and Proterozoic(?) Prospect Mountain Quartzite and the overlying Cambrian and Ordovician Tennessee Mountain Formation. This autochthon is overlain by three allochthonous plates each composed of a distinctive sequence of strata and having a distinctive internal structure. The structurally lowest plate is composed of the Havallah sequence, locally of Mississippian and Pennsylvanian age, which is folded on north-south trending axes. The next higher plate is composed of somewhat younger Pennsylvanian and Permian strata cut by east-west trending low-angle faults. The highest plate is composed of early Tertiary non-marine sedimentary and igneous rocks folded on varied but mainly north-south trending axes. The question of whether the allochthonous plates were emplaced by contractional or extensional forces is indeterminate from the local evidence. Mineral deposits include gold placers of moderate size and small pockets of base metals, none of which is currently being exploited.

Final acceptance testing of the LSST monolithic primary/tertiary mirror

NASA Astrophysics Data System (ADS)

Tuell, Michael T.; Burge, James H.; Cuerden, Brian; Gressler, William; Martin, Hubert M.; West, Steven C.; Zhao, Chunyu

2014-07-01

The Large Synoptic Survey Telescope (LSST) is a three-mirror wide-field survey telescope with the primary and tertiary mirrors on one monolithic substrate1. This substrate is made of Ohara E6 borosilicate glass in a honeycomb sandwich, spin cast at the Steward Observatory Mirror Lab at The University of Arizona2. Each surface is aspheric, with the specification in terms of conic constant error, maximum active bending forces and finally a structure function specification on the residual errors3. There are high-order deformation terms, but with no tolerance, any error is considered as a surface error and is included in the structure function. The radii of curvature are very different, requiring two independent test stations, each with instantaneous phase-shifting interferometers with null correctors. The primary null corrector is a standard two-element Offner null lens. The tertiary null corrector is a phase-etched computer-generated hologram (CGH). This paper details the two optical systems and their tolerances, showing that the uncertainty in measuring the figure is a small fraction of the structure function specification. Additional metrology includes the radii of curvature, optical axis locations, and relative surface tilts. The methods for measuring these will also be described along with their tolerances.

FuncPatch: a web server for the fast Bayesian inference of conserved functional patches in protein 3D structures.

PubMed

Huang, Yi-Fei; Golding, G Brian

2015-02-15

A number of statistical phylogenetic methods have been developed to infer conserved functional sites or regions in proteins. Many methods, e.g. Rate4Site, apply the standard phylogenetic models to infer site-specific substitution rates and totally ignore the spatial correlation of substitution rates in protein tertiary structures, which may reduce their power to identify conserved functional patches in protein tertiary structures when the sequences used in the analysis are highly similar. The 3D sliding window method has been proposed to infer conserved functional patches in protein tertiary structures, but the window size, which reflects the strength of the spatial correlation, must be predefined and is not inferred from data. We recently developed GP4Rate to solve these problems under the Bayesian framework. Unfortunately, GP4Rate is computationally slow. Here, we present an intuitive web server, FuncPatch, to perform a fast approximate Bayesian inference of conserved functional patches in protein tertiary structures. Both simulations and four case studies based on empirical data suggest that FuncPatch is a good approximation to GP4Rate. However, FuncPatch is orders of magnitudes faster than GP4Rate. In addition, simulations suggest that FuncPatch is potentially a useful tool complementary to Rate4Site, but the 3D sliding window method is less powerful than FuncPatch and Rate4Site. The functional patches predicted by FuncPatch in the four case studies are supported by experimental evidence, which corroborates the usefulness of FuncPatch. The software FuncPatch is freely available at the web site, http://info.mcmaster.ca/yifei/FuncPatch golding@mcmaster.ca Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Analysis of colonoscopic perforations at a local clinic and a tertiary hospital.

PubMed

Sagawa, Toshihiko; Kakizaki, Satoru; Iizuka, Haruhisa; Onozato, Yasuhiro; Sohara, Naondo; Okamura, Shinichi; Mori, Masatomo

2012-09-21

To define the clinical characteristics, and to assess the management of colonoscopic complications at a local clinic. A retrospective review of the medical records was performed for the patients with iatrogenic colon perforations after endoscopy at a local clinic between April 2006 and December 2010. Data obtained from a tertiary hospital in the same region were also analyzed. The underlying conditions, clinical presentations, perforation locations, treatment types (operative or conservative) and outcome data for patients at the local clinic and the tertiary hospital were compared. A total of 10  826 colonoscopies, and 2625 therapeutic procedures were performed at a local clinic and 32  148 colonoscopies, and 7787 therapeutic procedures were performed at the tertiary hospital. The clinic had no perforations during diagnostic colonoscopy and 8 (0.3%) perforations were determined to be related to therapeutic procedures. The perforation rates in each therapeutic procedure were 0.06% (1/1609) in polypectomy, 0.2% (2/885) in endoscopic mucosal resection (EMR), and 3.8% (5/131) in endoscopic submucosal dissection (ESD). Perforation rates for ESD were significantly higher than those for polypectomy or EMR (P < 0.01). All of these patients were treated conservatively. On the other hand, three (0.01%) perforation cases were observed among the 24  361 diagnostic procedures performed, and these cases were treated with surgery in a tertiary hospital. Six perforations occurred with therapeutic endoscopy (perforation rate, 0.08%; 1 per 1298 procedures). Perforation rates for specific procedure types were 0.02% (1 per 5500) for polypectomy, 0.17% (1 per 561) for EMR, 2.3% (1 per 43) for ESD in the tertiary hospital. There were no differences in the perforation rates for each therapeutic procedure between the clinic and the tertiary hospital. The incidence of iatrogenic perforation requiring surgical treatment was quite low in both the clinic and the tertiary hospital. No procedure-related mortalities occurred. Performing closure with endoscopic clipping reduced the C-reactive protein (CRP) titers. The mean maximum CRP titer was 2.9 ± 1.6 mg/dL with clipping and 9.7 ± 6.2 mg/dL without clipping, respectively (P < 0.05). An operation is indicated in the presence of a large perforation, and in the setting of generalized peritonitis or ongoing sepsis. Although we did not experience such case in the clinic, patients with large perforations should be immediately transferred to a tertiary hospital. Good relationships between local clinics and nearby tertiary hospitals should therefore be maintained. It was therefore found to be possible to perform endoscopic treatment at a local clinic when sufficient back up was available at a nearby tertiary hospital.

Protein Structure

ERIC Educational Resources Information Center

Asmus, Elaine Garbarino

2007-01-01

Individual students model specific amino acids and then, through dehydration synthesis, a class of students models a protein. The students clearly learn amino acid structure, primary, secondary, tertiary, and quaternary structure in proteins and the nature of the bonds maintaining a protein's shape. This activity is fun, concrete, inexpensive and…

Replica exchange molecular dynamics simulation of structure variation from α/4β-fold to 3α-fold protein.

PubMed

Lazim, Raudah; Mei, Ye; Zhang, Dawei

2012-03-01

Replica exchange molecular dynamics (REMD) simulation provides an efficient conformational sampling tool for the study of protein folding. In this study, we explore the mechanism directing the structure variation from α/4β-fold protein to 3α-fold protein after mutation by conducting REMD simulation on 42 replicas with temperatures ranging from 270 K to 710 K. The simulation began from a protein possessing the primary structure of GA88 but the tertiary structure of GB88, two G proteins with "high sequence identity." Albeit the large Cα-root mean square deviation (RMSD) of the folded protein (4.34 Å at 270 K and 4.75 Å at 304 K), a variation in tertiary structure was observed. Together with the analysis of secondary structure assignment, cluster analysis and principal component, it provides insights to the folding and unfolding pathway of 3α-fold protein and α/4β-fold protein respectively paving the way toward the understanding of the ongoings during conformational variation.

RaptorX server: a resource for template-based protein structure modeling.

PubMed

Källberg, Morten; Margaryan, Gohar; Wang, Sheng; Ma, Jianzhu; Xu, Jinbo

2014-01-01

Assigning functional properties to a newly discovered protein is a key challenge in modern biology. To this end, computational modeling of the three-dimensional atomic arrangement of the amino acid chain is often crucial in determining the role of the protein in biological processes. We present a community-wide web-based protocol, RaptorX server ( http://raptorx.uchicago.edu ), for automated protein secondary structure prediction, template-based tertiary structure modeling, and probabilistic alignment sampling.Given a target sequence, RaptorX server is able to detect even remotely related template sequences by means of a novel nonlinear context-specific alignment potential and probabilistic consistency algorithm. Using the protocol presented here it is thus possible to obtain high-quality structural models for many target protein sequences when only distantly related protein domains have experimentally solved structures. At present, RaptorX server can perform secondary and tertiary structure prediction of a 200 amino acid target sequence in approximately 30 min.

Paleomagnetic Results From the Mid-Tertiary Cripple Creek Diatreme Complex

NASA Astrophysics Data System (ADS)

Rampe, J. S.; Geissman, J. W.; Melker, M.

2001-12-01

The Cripple Creek diatreme complex, located about 30 km southwest of Pikes Peak, Colorado, is host to gold and high grade telluride deposits associated with mid-Tertiary alkaline magmatism. Formation of the diatreme took place between about 32.5 and 28.7 Ma, based on previously reported ArAr age determinations. The complex consists of breccia (the primary rock type), that was subsequently intruded by aphanitic phonolite, porphyritic phonolite, phonotephrite, and finally lamprophyre. Rocks presently at the surface were emplaced within a few kilometers of the paleosurface, followed by hydrothermal activity resulting in pervasive K metasomatism and gold mineralization. Mineralized deposits within the diatreme are currently being mined in an open pit fashion allowing for fresh three dimensional exposures of all representative rock types in the district. The Front Fange of Colorado, since cessation of northeast-directed Laramide compression, is characterized by east-west Rio Grande rift extension. Determining Laramide and younger deformation in the Front Range of Colorado is diffucult due to the dominance of Laramide structures and exposed Precambrian rocks with complex structural histories. Structures that affect the Cripple Creek diatreme complex and host Precambrian crystalline rocks clearly were active after intrusive activity and therefore reflect tectonism in the Front Range since early diatreme formation. Over 100 sites have been collected from all representative rock types in the district, with eight to ten oriented samples per site. Results indicate that the materials are capable of carrying geologically stable magnetizations and generally reveal excellent magnetization behavior using both AF and thermal methods. Many sites are associated with contact and breccia tests. Site mean directions are of both normal (D = 5.0° , I = 67.5° , α 95 = 6.4, κ = 89.2), N = 7 and reverse polarity (D = 162.2° , I = -67.3° , α 95 = 4.2, κ = 61.1) N =13; with site mean directions steeper than the expected mid-Tertiary polarity direction. Also, some sites exhibit multiple component behavior with both normal and reverse polarity magnetizations that are well defined (D = 29.7° , I = 72.5° , α 95 = 9.2, κ = 28.4) N = 10 and (D = 173.6° , I = -64.1° , α 95 = 3.1, κ = 594.8) N = 5, in aphanitic phonolite site CC89. We interpret these results to indicate that diatreme formation took place over at least one magnetic reversal and that the diatreme was modestly deformed resulting in north-side down tilting.

Geologic framework of lower Cook Inlet, Alaska

USGS Publications Warehouse

Fisher, M.A.; Magoon, L.B.

1978-01-01

Three seismic reflectors are present throughout the lower Cook Inlet basin and can be correlated with onshore geologic features. The reflections come from unconformities at the base of the Tertiary sequence, at the base of Upper Cretaceous rocks, and near the base of Upper Jurassic strata. A contour map of the deepest horizon shows that Mesozoic rocks are formed into a northeast-trending syncline. Along the southeast flank of the basin, the northwest-dipping Mesozoic rocks are truncated at the base of Tertiary rocks. The Augustine-Seldovia arch trends across the basin axis between Augustine Island and Seldovia. Tertiary rocks thin onto the arch from the north and south. Numerous anticlines, smaller in structural relief and breadth than the Augustine-Seldovia arch, trend northeast parallel with the basin, and intersect the arch at oblique angles. The stratigraphic record shows four cycles of sedimentation and tectonism that are bounded by three regional unconformities in lower Cook Inlet and by four thrust faults and the modern Benioff zone in flysch rocks of the Kenai Peninsula and the Gulf of Alaska. The four cycles of sedimentation are, from oldest to youngest, the early Mesozoic, late Mesozoic, early Cenozoic, and late Cenozoic. Data on organic geochemistry of the rocks from one well suggest that Middle Jurassic strata may be a source of hydrocarbons. Seismic data show that structural traps are formed by northeast-trending anticlines and by structures formed at the intersections of these anticlines with the transbasin arch. Stratigraphic traps may be formed beneath the unconformity at the base of Tertiary strata and beneath unconformities within Mesozoic strata.

Long-range tertiary interactions in single hammerhead ribozymes bias motional sampling toward catalytically active conformations

PubMed Central

McDowell, S. Elizabeth; Jun, Jesse M.; Walter, Nils G.

2010-01-01

Enzymes generally are thought to derive their functional activity from conformational motions. The limited chemical variation in RNA suggests that such structural dynamics may play a particularly important role in RNA function. Minimal hammerhead ribozymes are known to cleave efficiently only in ∼10-fold higher than physiologic concentrations of Mg2+ ions. Extended versions containing native loop–loop interactions, however, show greatly enhanced catalytic activity at physiologically relevant Mg2+ concentrations, for reasons that are still ill-understood. Here, we use Mg2+ titrations, activity assays, ensemble, and single molecule fluorescence resonance energy transfer (FRET) approaches, combined with molecular dynamics (MD) simulations, to ask what influence the spatially distant tertiary loop–loop interactions of an extended hammerhead ribozyme have on its structural dynamics. By comparing hammerhead variants with wild-type, partially disrupted, and fully disrupted loop–loop interaction sequences we find that the tertiary interactions lead to a dynamic motional sampling that increasingly populates catalytically active conformations. At the global level the wild-type tertiary interactions lead to more frequent, if transient, encounters of the loop-carrying stems, whereas at the local level they lead to an enrichment in favorable in-line attack angles at the cleavage site. These results invoke a linkage between RNA structural dynamics and function and suggest that loop–loop interactions in extended hammerhead ribozymes—and Mg2+ ions that bind to minimal ribozymes—may generally allow more frequent access to a catalytically relevant conformation(s), rather than simply locking the ribozyme into a single active state. PMID:20921269

Exploration of Novel Chemical Space: Synthesis and in vitro Evaluation of N-Functionalized Tertiary Sulfonimidamides.

PubMed

Izzo, Flavia; Schäfer, Martina; Lienau, Philip; Ganzer, Ursula; Stockman, Robert; Lücking, Ulrich

2018-05-04

An unprecedented set of structurally diverse sulfonimidamides (47 compounds) has been prepared by various N-functionalization reactions of tertiary =NH sulfonimidamide 2 aa. These N-functionalization reactions of model compound 2 aa include arylation, alkylation, trifluoromethylation, cyanation, sulfonylation, alkoxycarbonylation (carbamate formation) and aminocarbonylation (urea formation). Small molecule X-ray analyses of selected N-functionalized products are reported. To gain further insight into the properties of sulfonimidamides relevant to medicinal chemistry, a variety of structurally diverse reaction products were tested in selected in vitro assays. The described N-functionalization reactions provide a short and efficient approach to structurally diverse sulfonimidamides which have been the subject of recent, growing interest in the life sciences. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Unraveling double stranded alpha-helical coiled coils: an x-ray diffraction study on hard alpha-keratin fibers.

PubMed

Kreplak, L; Doucet, J; Briki, F

2001-04-15

Transformations of proteins secondary and tertiary structures are generally studied in globular proteins in solution. In fibrous proteins, such as hard alpha-keratin, that contain long and well-defined double stranded alpha-helical coiled coil domains, such study can be directly done on the native fibrous tissue. In order to assess the structural behavior of the coiled coil domains under an axial mechanical stress, wide angle x-ray scattering and small angle x-ray scattering experiments have been carried out on stretched horse hair fibers at relative humidity around 30%. Our observations of the three major axial spacings as a function of the applied macroscopic strain have shown two rates. Up to 4% macroscopic strain the coiled coils were slightly distorted but retained their overall conformation. Above 4% the proportion of coiled coil domains progressively decreased. The main and new result of our study is the observation of the transition from alpha-helical coiled coils to disordered chains instead of the alpha-helical coiled coil to beta-sheet transition that occurs in wet fibers.

Non-Escherichia coli versus Escherichia coli community-acquired urinary tract infections in children hospitalized in a tertiary center: relative frequency, risk factors, antimicrobial resistance and outcome.

PubMed

Marcus, Nir; Ashkenazi, Shai; Yaari, Arnon; Samra, Zmira; Livni, Gilat

2005-07-01

Currently hospitalization for children with urinary tract infections (UTIs) is reserved for severe or complicated cases. Changes may have taken place in the characteristics and causative uropathogens of hospital-treated community-acquired UTI. To study children hospitalized in a tertiary center with community-acquired UTI, compare Escherichia coli and non-E. coli UTI, define predictors for non-E. coli UTI and elucidate the appropriate therapeutic approach. A prospective clinical and laboratory study from 2001 through 2002 in a tertiary pediatric medical center. Patients were divided by results of the urine culture into E. coli and non-E. coli UTI groups, which were compared. Of 175 episodes of culture-proved UTI, 70 (40%) were caused by non-E. coli pathogens. Non-E. coli UTI was more commonly found in children who were male (P = 0.005), who had underlying renal abnormalities (P = 0.0085) and who had received antibiotic therapy in the prior month (P = 0.0009). Non-E. coli uropathogens were often resistant to antibiotics usually recommended for initial therapy for UTI, including cephalosporins and aminoglycosides; 19% were initially treated with inappropriate empiric intravenous antibiotics (compared with 2% for E. coli UTI, P = 0.0001), with a longer hospitalization. Current treatment routines are often inappropriate for hospitalized children with non-E. coli UTI, which is relatively common in this population. The defined risk factors associated with non-E. coli UTIs and its antimicrobial resistance patterns should be considered to improve empiric antibiotic therapy for these infections.

Shahejie-Shahejie/Guantao/Wumishan and Carboniferous/Permian Coal-Paleozoic Total Petroleum Systems in the Bohaiwan Basin, China (based on geologic studies for the 2000 World Energy Assessment Project of the U.S. Geological Survey)

USGS Publications Warehouse

Ryder, Robert T.; Qiang, Jin; McCabe, Peter J.; Nuccio, Vito F.; Persits, Felix

2012-01-01

This report discusses the geologic framework and petroleum geology used to assess undiscovered petroleum resources in the Bohaiwan basin province for the 2000 World Energy Assessment Project of the U.S. Geological Survey. The Bohaiwan basin in northeastern China is the largest petroleum-producing region in China. Two total petroleum systems have been identified in the basin. The first, the Shahejie&ndashShahejie/Guantao/Wumishan Total Petroleum System, involves oil and gas generated from mature pods of lacustrine source rock that are associated with six major rift-controlled subbasins. Two assessment units are defined in this total petroleum system: (1) a Tertiary lacustrine assessment unit consisting of sandstone reservoirs interbedded with lacustrine shale source rocks, and (2) a pre-Tertiary buried hills assessment unit consisting of carbonate reservoirs that are overlain unconformably by Tertiary lacustrine shale source rocks. The second total petroleum system identified in the Bohaiwan basin is the Carboniferous/Permian Coal–Paleozoic Total Petroleum System, a hypothetical total petroleum system involving natural gas generated from multiple pods of thermally mature coal beds. Low-permeability Permian sandstones and possibly Carboniferous coal beds are the reservoir rocks. Most of the natural gas is inferred to be trapped in continuous accumulations near the center of the subbasins. This total petroleum system is largely unexplored and has good potential for undiscovered gas accumulations. One assessment unit, coal-sourced gas, is defined in this total petroleum system.

Reduction in lipophilicity improved the solubility, plasma–protein binding, and permeability of tertiary sulfonamide RORc inverse agonists

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

Fauber, Benjamin P.; René, Olivier; de Leon Boenig, Gladys

2014-08-01

Using structure-based drug design principles, we identified opportunities to reduce the lipophilicity of our tertiary sulfonamide RORc inverse agonists. The new analogs possessed improved RORc cellular potencies with >77-fold selectivity for RORc over other nuclear receptors in our cell assay suite. The reduction in lipophilicity also led to an increased plasma–protein unbound fraction and improvements in cellular permeability and aqueous solubility.

ProTSAV: A protein tertiary structure analysis and validation server.

PubMed

Singh, Ankita; Kaushik, Rahul; Mishra, Avinash; Shanker, Asheesh; Jayaram, B

2016-01-01

Quality assessment of predicted model structures of proteins is as important as the protein tertiary structure prediction. A highly efficient quality assessment of predicted model structures directs further research on function. Here we present a new server ProTSAV, capable of evaluating predicted model structures based on some popular online servers and standalone tools. ProTSAV furnishes the user with a single quality score in case of individual protein structure along with a graphical representation and ranking in case of multiple protein structure assessment. The server is validated on ~64,446 protein structures including experimental structures from RCSB and predicted model structures for CASP targets and from public decoy sets. ProTSAV succeeds in predicting quality of protein structures with a specificity of 100% and a sensitivity of 98% on experimentally solved structures and achieves a specificity of 88%and a sensitivity of 91% on predicted protein structures of CASP11 targets under 2Å.The server overcomes the limitations of any single server/method and is seen to be robust in helping in quality assessment. ProTSAV is freely available at http://www.scfbio-iitd.res.in/software/proteomics/protsav.jsp. Copyright © 2015 Elsevier B.V. All rights reserved.

Protein Detection via Direct Enzymatic Amplification of Short DNA Aptamers

PubMed Central

Fischer, Nicholas O.; Tarasow, Theodore M.; Tok, Jeffrey B.-H.

2008-01-01

Aptamers are single-stranded nucleic acids that fold into defined tertiary structures to bind target molecules with high specificities and affinities. DNA aptamers have garnered much interest as recognition elements for biodetection and diagnostic applications due to their small size, ease of discovery and synthesis, and chemical and thermal stability. Herein, we describe the design and application of a short DNA molecule capable of both protein target binding and amplifiable bioreadout processes. As both recognition and readout capabilities are incorporated into a single DNA molecule, tedious conjugation procedures required for protein-DNA hybrids can be omitted. The DNA aptamer is designed to be amplified directly by either the polymerase chain reaction (PCR) or rolling circle amplification (RCA) processes, taking advantage of real-time amplification monitoring techniques for target detection. A combination of both RCA and PCR provides a wide protein target dynamic range (1 μM to 10 pM). PMID:17980857

Evolution of silicic magma in the upper crust: the mid-Tertiary Latir volcanic field and its cogenetic granitic batholith, northern New Mexico, USA

USGS Publications Warehouse

Lipman, P.W.

1988-01-01

Structural and topographic relief along the eastern margin of the Rio Grande rift, northern New Mexico, provides a remarkable cross-section through the 26-Ma Questa caldera and cogenetic volcanic and plutonic rocks of the Latir field. Exposed levels increase in depth from mid-Tertiary depositional surfaces in northern parts of the igneous complex to plutonic rocks originally at 3-5 km depths in the S. Erosional remnants of an ash-flow sheet of weakly peralkaline rhyolite (Amalia Tuff) and andesitic to dactitic precursor lavas, disrupted by rift-related faults, are preserved as far as 45 km beyond their sources at the Questa caldera. Broadly comagmatic 26 Ma batholithic granitic rocks, exposed over an area of 20 by 35 km, range from mesozonal granodiorite to epizonal porphyritic granite and aplite; shallower and more silicic phases are mostly within the caldera. Compositionally and texturally distinct granites defined resurgent intrusions within the caldera and discontinuous ring dikes along its margins: a batholithic mass of granodiorite extends 20 km S of the caldera and locally grades vertically to granite below its flat-lying roof. A negative Bouguer gravity anomaly (15-20 mgal), which encloses exposed granitic rocks and coincides with boundaries of the Questa caldera, defined boundaries of the shallow batholith, emplaced low in the volcanic sequence and in underlying Precambrian rocks. Paleomagnetic pole positions indicate that successively crystallised granitic plutons cooled through Curie temperatures during the time of caldera formation, initial regional extension, and rotational tilting of the volcanic rocks. Isotopic ages for most intrusions are indistinguishable from the volcanic rocks. These relations indicate that the batholithic complex broadly represents the source magma for the volcanic rocks, into which the Questa caldera collapsed, and that the magma was largely liquid during regional tectonic disruption. -from Author

Disruptive Innovation, Labor Markets, and Big Valley STEM School: Network Analysis in STEM Education

ERIC Educational Resources Information Center

Ellison, Scott; Allen, Ben

2018-01-01

A defining characteristic of contemporary trends in global education policy is the promotion of STEM learning in the primary, secondary, and tertiary sectors of education as a means to generate innovation and prosperity in the economy. Intertwined with common sensical assumptions about future labor markets and the transformative potential of…

Self-Directed Learning Characteristics: Making Learning Personal, Empowering and Successful

ERIC Educational Resources Information Center

du Toit-Brits, Charlene; van Zyl, Chris-Mari

2017-01-01

Due to the speedy emergent investigation in self-directed learning (SDL) over the past 40 years, SDL is an education technique used progressively within tertiary institutions. SDL can be well-defined in terms of the amount of accountability the student accepts for his or her own learning. The self-directed students regarding learning take control…

Coanda injection system for axially staged low emission combustors

DOEpatents

Evulet, Andrei Tristan [Clifton Park, NY; Varatharajan, Balachandar [Cincinnati, OH; Kraemer, Gilbert Otto [Greer, SC; ElKady, Ahmed Mostafa [Niskayuna, NY; Lacy, Benjamin Paul [Greer, SC

2012-05-15

The low emission combustor includes a combustor housing defining a combustion chamber having a plurality of combustion zones. A liner sleeve is disposed in the combustion housing with a gap formed between the liner sleeve and the combustor housing. A secondary nozzle is disposed along a centerline of the combustion chamber and configured to inject a first fluid comprising air, at least one diluent, fuel, or combinations thereof to a downstream side of a first combustion zone among the plurality of combustion zones. A plurality of primary fuel nozzles is disposed proximate to an upstream side of the combustion chamber and located around the secondary nozzle and configured to inject a second fluid comprising air and fuel to an upstream side of the first combustion zone. The combustor also includes a plurality of tertiary coanda nozzles. Each tertiary coanda nozzle is coupled to a respective dilution hole. The tertiary coanda nozzles are configured to inject a third fluid comprising air, at least one other diluent, fuel, or combinations thereof to one or more remaining combustion zones among the plurality of combustion zones.

Inter-species chimeras of leukaemia inhibitory factor define a major human receptor-binding determinant.

PubMed Central

Owczarek, C M; Layton, M J; Metcalf, D; Lock, P; Willson, T A; Gough, N M; Nicola, N A

1993-01-01

Human leukaemia inhibitory factor (hLIF) binds to both human and mouse LIF receptors (LIF-R), while mouse LIF (mLIF) binds only to mouse LIF-R. Moreover, hLIF binds with higher affinity to the mLIF-R than does mLIF. In order to define the regions of the hLIF molecule responsible for species-specific interaction with the hLIF-R and for the unusual high-affinity binding to the mLIF-R, a series of 15 mouse/human LIF hybrids has been generated. Perhaps surprisingly, both of these properties mapped to the same region of the hLIF molecule. The predominant contribution was from residues in the loop linking the third and fourth helices, with lesser contributions from residues in the third helix and the loop connecting the second and third helices in the predicted three-dimensional structure. Since all chimeras retained full biological activity and receptor-binding activity on mouse cells, and there was little variation in the specific biological activity of the purified proteins, it can be concluded that the overall secondary and tertiary structures of each chimera were intact. This observation also implied that the primary binding sites on mLIF and hLIF for the mLIF-R were unaltered by inter-species domain swapping. Consequently, the site on the hLIF molecule that confers species-specific binding to the hLIF-R and higher affinity binding to the mLIF-R, must constitute an additional interaction site to that used by both mLIF and hLIF to bind to the mLIF-R. These studies define a maximum of 15 amino acid differences between hLIF and mLIF that are responsible for the different properties of these proteins. Images PMID:8253075

Hydrostructural maps of the Death Valley regional flow system, Nevada and California

USGS Publications Warehouse

Potter, C.J.; Sweetkind, D.S.; Dickerson, R.P.; Killgore, M.L.

2002-01-01

The locations of principal faults and structural zones that may influence ground-water flow were compiled in support of a three-dimensional ground-water model for the Death Valley regional flow system (DVRFS), which covers 80,000 square km in southwestern Nevada and southeastern California. Faults include Neogene extensional and strike-slip faults and pre-Tertiary thrust faults. Emphasis was given to characteristics of faults and deformed zones that may have a high potential for influencing hydraulic conductivity. These include: (1) faulting that results in the juxtaposition of stratigraphic units with contrasting hydrologic properties, which may cause ground-water discharge and other perturbations in the flow system; (2) special physical characteristics of the fault zones, such as brecciation and fracturing, that may cause specific parts of the zone to act either as conduits or as barriers to fluid flow; (3) the presence of a variety of lithologies whose physical and deformational characteristics may serve to impede or enhance flow in fault zones; (4) orientation of a fault with respect to the present-day stress field, possibly influencing hydraulic conductivity along the fault zone; and (5) faults that have been active in late Pleistocene or Holocene time and areas of contemporary seismicity, which may be associated with enhanced permeabilities. The faults shown on maps A and B are largely from Workman and others (in press), and fit one or more of the following criteria: (1) faults that are more than 10 km in map length; (2) faults with more than 500 m of displacement; and (3) faults in sets that define a significant structural fabric that characterizes a particular domain of the DVRFS. The following fault types are shown: Neogene normal, Neogene strike-slip, Neogene low-angle normal, pre-Tertiary thrust, and structural boundaries of Miocene calderas. We have highlighted faults that have late Pleistocene to Holocene displacement (Piety, 1996). Areas of thick Neogene basin-fill deposits (thicknesses 1-2 km, 2-3 km, and >3 km) are shown on map A, based on gravity anomalies and depth-to-basement modeling by Blakely and others (1999). We have interpreted the positions of faults in the subsurface, generally following the interpretations of Blakely and others (1999). Where geophysical constraints are not present, the faults beneath late Tertiary and Quaternary cover have been extended based on geologic reasoning. Nearly all of these concealed faults are shown with continuous solid lines on maps A and B, in order to provide continuous structures for incorporation into the hydrogeologic framework model (HFM). Map A also shows the potentiometric surface, regional springs (25-35 degrees Celsius, D'Agnese and others, 1997), and cold springs (Turner and others, 1996).

Exploring Fold Space Preferences of New-born and Ancient Protein Superfamilies

PubMed Central

Edwards, Hannah; Abeln, Sanne; Deane, Charlotte M.

2013-01-01

The evolution of proteins is one of the fundamental processes that has delivered the diversity and complexity of life we see around ourselves today. While we tend to define protein evolution in terms of sequence level mutations, insertions and deletions, it is hard to translate these processes to a more complete picture incorporating a polypeptide's structure and function. By considering how protein structures change over time we can gain an entirely new appreciation of their long-term evolutionary dynamics. In this work we seek to identify how populations of proteins at different stages of evolution explore their possible structure space. We use an annotation of superfamily age to this space and explore the relationship between these ages and a diverse set of properties pertaining to a superfamily's sequence, structure and function. We note several marked differences between the populations of newly evolved and ancient structures, such as in their length distributions, secondary structure content and tertiary packing arrangements. In particular, many of these differences suggest a less elaborate structure for newly evolved superfamilies when compared with their ancient counterparts. We show that the structural preferences we report are not a residual effect of a more fundamental relationship with function. Furthermore, we demonstrate the robustness of our results, using significant variation in the algorithm used to estimate the ages. We present these age estimates as a useful tool to analyse protein populations. In particularly, we apply this in a comparison of domains containing greek key or jelly roll motifs. PMID:24244135

Prediction of protein tertiary structure to low resolution: performance for a large and structurally diverse test set.

PubMed

Eyrich, V A; Standley, D M; Friesner, R A

1999-05-14

We report the tertiary structure predictions for 95 proteins ranging in size from 17 to 160 residues starting from known secondary structure. Predictions are obtained from global minimization of an empirical potential function followed by the application of a refined atomic overlap potential. The minimization strategy employed represents a variant of the Monte Carlo plus minimization scheme of Li and Scheraga applied to a reduced model of the protein chain. For all of the cases except beta-proteins larger than 75 residues, a native-like structure, usually 4-6 A root-mean-square deviation from the native, is located. For beta-proteins larger than 75 residues, the energy gap between native-like structures and the lowest energy structures produced in the simulation is large, so that low RMSD structures are not generated starting from an unfolded state. This is attributed to the lack of an explicit hydrogen bond term in the potential function, which we hypothesize is necessary to stabilize large assemblies of beta-strands. Copyright 1999 Academic Press.

Total Petroleum Systems of the Carpathian - Balkanian Basin Province of Romania and Bulgaria

USGS Publications Warehouse

Pawlewicz, Mark

2007-01-01

The U.S. Geological Survey defined the Moesian Platform Composite Total Petroleum System and the Dysodile Schist-Tertiary Total Petroleum System, which contain three assessment units, in the Carpathian-Balkanian Basin Province of Romania and Bulgaria. The Moesian Platform Assessment Unit, contained within the Moesian Platform Composite Total Petroleum System, is composed of Mesozoic and Cenozoic rocks within the Moesian platform region of southern Romania and northern Bulgaria and also within the Birlad depression in the northeastern platform area. In Romania, hydrocarbon sources are identified as carbonate rocks and bituminous claystones within the Middle Devonian, Middle Jurassic, Lower Cretaceous, and Neogene stratigraphic sequences. In the Birlad depression, Neogene pelitic strata have the best potential for generating hydrocarbons. In Bulgaria, Middle and Upper Jurassic shales are the most probable hydrocarbon sources. The Romania Flysch Zone Assessment Unit in the Dysodile Schist-Tertiary Total Petroleum System encompasses three structural and paleogeographic subunits within the Pre-Carpathian Mountains region: (1) the Getic depression, a segment of the Carpathian foredeep; (2) the flysch zone of the eastern Carpathian Mountains (also called the Marginal Fold nappe); and (3) the Miocene zone (also called the Sub-Carpathian nappe). Source rocks are interpreted to be Oligocene dysodile schist and black claystone, along with Miocene black claystone and marls. Also part of the Dysodile Schist-Tertiary Total Petroleum System is the Romania Ploiesti Zone Assessment Unit, which includes a zone of diapir folds. This zone lies between the Rimnicu Sarat and Dinibovita valleys and between the folds of the inner Carpathian Mountains and the external flanks of the Carpathian foredeep. The Oligocene Dysodile Schist is considered the main hydrocarbon source rock and Neogene black marls and claystones are likely secondary sources; all are thought to be at their maximum thermal maturation. Undiscovered resources in the Carpathian-Balkanian Basin Province are estimated, at the mean, to be 2,076 billion cubic feet of gas, 1,013 million barrels of oil, and 116 million barrels of natural gas liquids.

Pliocene transpressional modification of depositional basins by convergent thrusting adjacent to the "Big Bend" of the San Andreas fault: An example from Lockwood Valley, southern California

USGS Publications Warehouse

Kellogg, K.S.; Minor, S.A.

2005-01-01

The "Big Bend" of the San Andreas fault in the western Transverse Ranges of southern California is a left stepping flexure in the dextral fault system and has long been recognized as a zone of relatively high transpression compared to adjacent regions. The Lockwood Valley region, just south of the Big Bend, underwent a profound change in early Pliocene time (???5 Ma) from basin deposition to contraction, accompanied by widespread folding and thrusting. This change followed the recently determined initiation of opening of the northern Gulf of California and movement along the southern San Andreas fault at about 6.1 Ma, with the concomitant formation of the Big Bend. Lockwood Valley occupies a 6-km-wide, fault-bounded structural basin in which converging blocks of Paleoproterozoic and Cretaceous crystalline basement and upper Oligocene and lower Miocene sedimentary rocks (Plush Ranch Formation) were thrust over Miocene and Pliocene basin-fill sedimentary rocks (in ascending order, Caliente Formation, Lockwood Clay, and Quatal Formation). All the pre-Quatal sedimentary rocks and most of the Pliocene Quatal Formation were deposited during a mid-Tertiary period of regional transtension in a crustal block that underwent little clockwise vertical-axis rotation as compared to crustal blocks to the south. Ensuing Pliocene and Quaternary transpression in the Big Bend region began during deposition of the poorly dated Quatal Formation and was marked by four converging thrust systems, which decreased the areal extent of the sedimentary basin and formed the present Lockwood Valley structural basin. None of the thrusts appears presently active. Estimated shortening across the center of the basin was about 30 percent. The fortnerly defined eastern Big Pine fault, now interpreted to be two separate, oppositely directed, contractional reverse or thrust faults, marks the northwestern structural boundary of Lockwood Valley. The complex geometry of the Lockwood Valley basin is similar to other Tertiary structural basins in southern California, such those that underlie Cuyama Valley, the Ridge basin, and the east Ventura basin.

Improving mental health service users' with medical co-morbidity transition between tertiary medical hospital and primary care services: a qualitative study.

PubMed

Cranwell, Kate; Polacsek, Meg; McCann, Terence V

2016-07-26

Mental health service users have high rates of medical co-morbidity but frequently experience problems accessing and transitioning between tertiary medical and primary care services. The aim of this study was to identify ways to improve service users' with medical co-morbidity care and experience during their transition between tertiary medical hospitals and primary care services. Experience-based co-design (EBCD) qualitative study incorporating a focus group discussion. The study took place in a large tertiary medical service, incorporating three medical hospitals, and primary care services, in Melbourne, Australia. A purposive sample of service users and their caregivers and tertiary medical and primary care clinicians participated in the focus group discussion, in August 2014. A semi-structured interview guide was used to inform data collection. A thematic analysis of the data was undertaken. Thirteen participants took part in the focus group interview, comprising 5 service users, 2 caregivers and 6 clinicians. Five themes were abstracted from the data, illustrating participants' perspectives about factors that facilitated (clinicians' expertise, engagement and accessibility enhancing transition) and presented as barriers (improving access pathways; enhancing communication and continuity of care; improving clinicians' attitudes; and increasing caregiver participation) to service users' progress through tertiary medical and primary care services. A sixth theme, enhancing service users' transition, incorporated three strategies to enhance their transition through tertiary medical and primary care services. EBCD is a useful approach to collaboratively develop strategies to improve service users' with medical co-morbidity and their caregivers' transition between tertiary medical and primary care services. A whole-of-service approach, incorporating policy development and implementation, change of practice philosophy, professional development education and support for clinicians, and acceptance of the need for caregiver participation, is required to improve service users' transition.

Three-residue turns in alpha/beta-peptides and their application in the design of tertiary structures.

PubMed

Sharma, Gangavaram V M; Nagendar, Pendem; Ramakrishna, Kallaganti V S; Chandramouli, Nagula; Choudhary, Madavi; Kunwar, Ajit C

2008-06-02

A new three-residue turn was serendipitously discovered in alpha/beta hybrid peptides derived from alternating C-linked carbo-beta-amino acids (beta-Caa) and L-Ala residues. The three-residue beta-alpha-beta turn at the C termini, nucleated by a helix at the N termini, resulted in helix-turn (HT) supersecondary structures in these peptides. The turn in the HT motif is stabilized by two H bonds-CO(i-2)-NH(i), with a seven-membered pseudoring (gamma turn) in the backward direction, and NH(i-2)-CO(i), with a 13-membered pseudoring in the forward direction (i being the last residue)--at the C termini. The study was extended to generalize the new three-residue turn (beta-alpha-beta) by using different alpha- and beta-amino acids. Furthermore, the HT motifs were efficiently converted, by an extension with helical oligomers at the C termini, into peptides with novel helix-turn-helix (HTH) tertiary structures. However, this resulted in the destabilization of the beta-alpha-beta turn with the concomitant nucleation of another three-residue turn, alpha-beta-beta, which is stabilized by 11- and 15-membered bifurcated H bonds. Extensive NMR spectroscopic studies were carried out to delineate the secondary and tertiary structures in these peptides, which are further supported by molecular dynamics (MD) investigations.

alpha-helical structural elements within the voltage-sensing domains of a K(+) channel.

PubMed

Li-Smerin, Y; Hackos, D H; Swartz, K J

2000-01-01

Voltage-gated K(+) channels are tetramers with each subunit containing six (S1-S6) putative membrane spanning segments. The fifth through sixth transmembrane segments (S5-S6) from each of four subunits assemble to form a central pore domain. A growing body of evidence suggests that the first four segments (S1-S4) comprise a domain-like voltage-sensing structure. While the topology of this region is reasonably well defined, the secondary and tertiary structures of these transmembrane segments are not. To explore the secondary structure of the voltage-sensing domains, we used alanine-scanning mutagenesis through the region encompassing the first four transmembrane segments in the drk1 voltage-gated K(+) channel. We examined the mutation-induced perturbation in gating free energy for periodicity characteristic of alpha-helices. Our results are consistent with at least portions of S1, S2, S3, and S4 adopting alpha-helical secondary structure. In addition, both the S1-S2 and S3-S4 linkers exhibited substantial helical character. The distribution of gating perturbations for S1 and S2 suggest that these two helices interact primarily with two environments. In contrast, the distribution of perturbations for S3 and S4 were more complex, suggesting that the latter two helices make more extensive protein contacts, possibly interfacing directly with the shell of the pore domain.

Effect of pulsed light on activity and structural changes of horseradish peroxidase

USDA-ARS?s Scientific Manuscript database

The objective of this research was to investigate the effects of pulsed light (PL) on the activity and structure of horseradish peroxidase (HRP) in buffer solution. Enzyme residual activities were measured after PL. Surface topography, secondary, and tertiary structures of HRP were determined using ...

Assembly-directed antivirals differentially bind quasiequivalent pockets to modify hepatitis B virus capsid tertiary and quaternary structure.

PubMed

Katen, Sarah P; Tan, Zhenning; Chirapu, Srinivas Reddy; Finn, M G; Zlotnick, Adam

2013-08-06

Hepatitis B virus (HBV) is a major cause of liver disease. Assembly of the HBV capsid is a critical step in virus production and an attractive target for new antiviral therapies. We determined the structure of HBV capsid in complex with AT-130, a member of the phenylpropenamide family of assembly effectors. AT-130 causes tertiary and quaternary structural changes but does not disrupt capsid structure. AT-130 binds a hydrophobic pocket that also accommodates the previously characterized heteroaryldihydropyrimidine compounds but favors a unique quasiequivalent location on the capsid surface. Thus, this pocket is a promiscuous drug-binding site and a likely target for different assembly effectors with a broad range of mechanisms of activity. That AT-130 successfully decreases virus production by increasing capsid assembly rate without disrupting capsid structure delineates a paradigm in antiviral design, that disrupting reaction timing is a viable strategy for assembly effectors of HBV and other viruses. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Development of an index system for the comprehensive evaluation on public health emergency events surveillance system in China].

PubMed

Hong, Zhiheng; Ni, Daxin; Cao, Yang; Meng, Ling; Tu, Wenxiao; Li, Leilei; Li, Qun; Jin, Lianmei

2015-06-01

To establish a comprehensive evaluation index system for the China Public Health Emergency Events Surveillance System (CPHEESS). A draft index system was built through literature review and under the consideration of the characteristics on CPHEESS. Delphi method was adapted to determine the final index system. The index system was divided into primary, secondary and tertiary levels. There were 4 primary indicators: System structure, Network platform, Surveillance implementation reports with Data analysis and utilization. There were 16 secondary and 70 tertiary indicators being set, with System structure including 14 tertiary indicators (accounted for 20.00%), 21 Network platforms (accounted for 30.00%). Twenty-four Surveillance implementation reports (accounted for 34.29%), 11 Data analysis and utilization (accounted for 15.71%). The average score of importance of each indicators was 4.29 (3.77-4.94), with an average coefficient variation as 0.14 (0.12-0.16). The mean Chronbach's α index was 0.84 (0.81-0.89). The adaptability of each related facilities indicator was specified. The primary indicators were set in accordance with the characteristics and goals of the surveillance systems. Secondary indicators provided key elements in the management and control of the system while the tertiary indicators were available and operative. The agreement rate of experts was high with good validity and reliability. This index system could be used for CPHEESS in future.

Pushing the size limit of de novo structure ensemble prediction guided by sparse SDSL-EPR restraints to 200 residues: The monomeric and homodimeric forms of BAX

PubMed Central

Fischer, Axel W.; Bordignon, Enrica; Bleicken, Stephanie; García-Sáez, Ana J.; Jeschke, Gunnar; Meiler, Jens

2016-01-01

Structure determination remains a challenge for many biologically important proteins. In particular, proteins that adopt multiple conformations often evade crystallization in all biologically relevant states. Although computational de novo protein folding approaches often sample biologically relevant conformations, the selection of the most accurate model for different functional states remains a formidable challenge, in particular, for proteins with more than about 150 residues. Electron paramagnetic resonance (EPR) spectroscopy can obtain limited structural information for proteins in well-defined biological states and thereby assist in selecting biologically relevant conformations. The present study demonstrates that de novo folding methods are able to accurately sample the folds of 192-residue long soluble monomeric Bcl-2-associated X protein (BAX). The tertiary structures of the monomeric and homodimeric forms of BAX were predicted using the primary structure as well as 25 and 11 EPR distance restraints, respectively. The predicted models were subsequently compared to respective NMR/X-ray structures of BAX. EPR restraints improve the protein-size normalized root-mean-square-deviation (RMSD100) of the most accurate models with respect to the NMR/crystal structure from 5.9 Å to 3.9 Å and from 5.7 Å to 3.3 Å, respectively. Additionally, the model discrimination is improved, which is demonstrated by an improvement of the enrichment from 5% to 15% and from 13% to 21%, respectively. PMID:27129417

Functional insights from proteome-wide structural modeling of Treponema pallidum subspecies pallidum, the causative agent of syphilis.

PubMed

Houston, Simon; Lithgow, Karen Vivien; Osbak, Kara Krista; Kenyon, Chris Richard; Cameron, Caroline E

2018-05-16

Syphilis continues to be a major global health threat with 11 million new infections each year, and a global burden of 36 million cases. The causative agent of syphilis, Treponema pallidum subspecies pallidum, is a highly virulent bacterium, however the molecular mechanisms underlying T. pallidum pathogenesis remain to be definitively identified. This is due to the fact that T. pallidum is currently uncultivatable, inherently fragile and thus difficult to work with, and phylogenetically distinct with no conventional virulence factor homologs found in other pathogens. In fact, approximately 30% of its predicted protein-coding genes have no known orthologs or assigned functions. Here we employed a structural bioinformatics approach using Phyre2-based tertiary structure modeling to improve our understanding of T. pallidum protein function on a proteome-wide scale. Phyre2-based tertiary structure modeling generated high-confidence predictions for 80% of the T. pallidum proteome (780/978 predicted proteins). Tertiary structure modeling also inferred the same function as primary structure-based annotations from genome sequencing pipelines for 525/605 proteins (87%), which represents 54% (525/978) of all T. pallidum proteins. Of the 175 T. pallidum proteins modeled with high confidence that were not assigned functions in the previously annotated published proteome, 167 (95%) were able to be assigned predicted functions. Twenty-one of the 175 hypothetical proteins modeled with high confidence were also predicted to exhibit significant structural similarity with proteins experimentally confirmed to be required for virulence in other pathogens. Phyre2-based structural modeling is a powerful bioinformatics tool that has provided insight into the potential structure and function of the majority of T. pallidum proteins and helped validate the primary structure-based annotation of more than 50% of all T. pallidum proteins with high confidence. This work represents the first T. pallidum proteome-wide structural modeling study and is one of few studies to apply this approach for the functional annotation of a whole proteome.

Revisiting the NMR structure of the ultrafast downhill folding protein gpW from bacteriophage λ.

PubMed

Sborgi, Lorenzo; Verma, Abhinav; Muñoz, Victor; de Alba, Eva

2011-01-01

GpW is a 68-residue protein from bacteriophage λ that participates in virus head morphogenesis. Previous NMR studies revealed a novel α+β fold for this protein. Recent experiments have shown that gpW folds in microseconds by crossing a marginal free energy barrier (i.e., downhill folding). These features make gpW a highly desirable target for further experimental and computational folding studies. As a step in that direction, we have re-determined the high-resolution structure of gpW by multidimensional NMR on a construct that eliminates the purification tags and unstructured C-terminal tail present in the prior study. In contrast to the previous work, we have obtained a full manual assignment and calculated the structure using only unambiguous distance restraints. This new structure confirms the α+β topology, but reveals important differences in tertiary packing. Namely, the two α-helices are rotated along their main axis to form a leucine zipper. The β-hairpin is orthogonal to the helical interface rather than parallel, displaying most tertiary contacts through strand 1. There also are differences in secondary structure: longer and less curved helices and a hairpin that now shows the typical right-hand twist. Molecular dynamics simulations starting from both gpW structures, and calculations with CS-Rosetta, all converge to our gpW structure. This confirms that the original structure has strange tertiary packing and strained secondary structure. A comparison of NMR datasets suggests that the problems were mainly caused by incomplete chemical shift assignments, mistakes in NOE assignment and the inclusion of ambiguous distance restraints during the automated procedure used in the original study. The new gpW corrects these problems, providing the appropriate structural reference for future work. Furthermore, our results are a cautionary tale against the inclusion of ambiguous experimental information in the determination of protein structures.

Network structure and concentration fluctuations in a series of elemental, binary, and tertiary liquids and glasses.

PubMed

Soper, Alan K

2010-10-13

Liquids and glasses continue to produce a lively debate about the nature of the disordered structure in these materials, and whether it is driven by longer range concentration or density fluctuations. One factor often lacking in these studies is an overview of a wide range of structures from which common features of and differences between materials can be identified. Here I examine the structure of a wide range of chain and network, elemental, binary and tertiary liquids and glasses, using available x-ray and neutron diffraction data and combining them with empirical potential structure refinement. Calculation of the Bhatia-Thornton number-number and concentration-concentration structure factors and distribution functions highlights common structural motifs that run through many of the series. It is found that the greatest structural overlap occurs where the nearest-neighbour and second-neighbour coordination numbers are similar for different materials. As these coordination numbers increase, so the structures undergo a sequence of characteristic changes involving increasingly bent bond angle distributions and increased packing fractions. In these regards liquid and amorphous phosphorus appear to be in a structural class of their own, combining both chain-like and network-like characteristics.

Water-Solubilized, Cap-Stabilized, Helical Polyalanines: Calibration Standards for NMR and CD Analyses

PubMed Central

Heitmann, Björn; Job, Gabriel E.; Kennedy, Robert J.; Walker, Sharon M.; Kemp, Daniel S.

2006-01-01

NMR and CD studies are reported for two length series of solubilized, spaced, highly helical polyalanines that are N-capped by the optimal helix stabilizer βAsp-Hel and C-capped by β-aminoalanine beta and that are studied in water at 2 °C, pH 1–8. NMR analysis yields a structural characterization of the peptide AcβAspHelAla8betaNH2 and selected members of one βAspHelAlanbeta series. At pH > 4.5 the βAspHel cap provides a preorganized triad of carboxylate anion and two amide residues that is complementary to the helical polyalanine N-terminus. The C-terminal β-aminoalanine assumes a helix-stabilizing conformation consistent with literature precedents. H(N)CO NMR experiments applied to capped, uniformly 13C- and 15N-labeled Ala8 and Ala12 peptides define Alan hydrogen bonding signatures as α-helical without detectable 310 character. Relative NH→ND exchange rates yield site protection factors PFi that define uniquely high fractional helicities FH for the peptide Alan regions. These Alan calibration series, studied in water and lacking helix-stabilizing tertiary structure, yield the first 13C NMR chemical shifts, 3JHNHα coupling constants, and CD ellipticities [θMolar]λ,n characteristic of a fully helical alanine within an Alan context. CD data are used to assign parameters X and [θ]λ,∞, required for rigorous calculation of FH values from CD ellipticities. PMID:15701003

Tertiary lymphoid structures in cancer and beyond.

PubMed

Dieu-Nosjean, Marie-Caroline; Goc, Jérémy; Giraldo, Nicolas A; Sautès-Fridman, Catherine; Fridman, Wolf Herman

2014-11-01

Tertiary lymphoid structures (TLS) are ectopic lymphoid formations found in inflamed, infected, or tumoral tissues. They exhibit all the characteristics of structures in the lymph nodes (LN) associated with the generation of an adaptive immune response, including a T cell zone with mature dendritic cells (DC), a germinal center with follicular dendritic cells (FDC) and proliferating B cells, and high endothelial venules (HEV). In this review, we discuss evidence for the roles of TLS in chronic infection, autoimmunity, and cancer, and address the question of whether TLS present beneficial or deleterious effects in these contexts. We examine the relationship between TLS in tumors and patient prognosis, and discuss the potential role of TLS in building and/or maintaining local immune responses and how this understanding may guide therapeutic interventions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Marked variation in newborn resuscitation practice: A national survey in the UK☆

PubMed Central

Mann, Chantelle; Ward, Carole; Grubb, Mark; Hayes-Gill, Barrie; Crowe, John; Marlow, Neil; Sharkey, Don

2012-01-01

Background Although international newborn resuscitation guidance has been in force for some time, there are no UK data on current newborn resuscitation practices. Objective Establish delivery room (DR) resuscitation practices in the UK, and identify any differences between neonatal intensive care units (NICU), and other local neonatal services. Methods We conducted a structured two-stage survey of DR management, among UK neonatal units during 2009–2010 (n = 192). Differences between NICU services (tertiary level) and other local neonatal services (non-tertiary) were analysed using Fisher's exact and Student's t-tests. Results There was an 89% response rate (n = 171). More tertiary NICUs institute DR CPAP than non-tertiary units (43% vs. 16%, P = 0.0001) though there was no significant difference in frequency of elective intubation and surfactant administration for preterm babies. More tertiary units commence DR resuscitation in air (62% vs. 29%, P < 0.0001) and fewer in 100% oxygen (11% vs. 41%, P < 0.0001). Resuscitation of preterm babies in particular, commences with air in 56% of tertiary units. Significantly more tertiary units use DR pulse oximeters (58% vs. 29%, P < 0.01) and titrate oxygen based on saturations. Almost all services use occlusive wrapping to maintain temperature for preterm infants. Conclusions In the UK, there are many areas of good evidence based DR practice. However, there is marked variation in management, including between units of different designation, suggesting a need to review practice to fulfil new resuscitation guidance, which will have training and resource implications. PMID:22245743

A third of patients treated at a tertiary-level surgical service could be treated at a secondary-level facility.

PubMed

Van Straten, S; Stannard, C; Bulabula, J; Boodhia, K; Paul, K; Leong, J; Klipin, M J

2017-08-25

South Africa (SA) has an overburdened public healthcare system. Some patients admitted to Charlotte Maxeke Johannesburg Academic Hospital (CMJAH), SA, may not require tertiary care, but the numbers and details are uncertain. Clinical research in SA is limited by scarce skills and limited access to data. To determine the proportion of and length of stay for secondary-, tertiary- and quaternary-level patients discharged from the Department of Surgery at CMJAH over 1 year. This is a retrospective analysis of electronic discharge (ED) summaries from the Department of Surgery at CMJAH between 1 April 2015 and 1 April 2016. An SQL query of the database generated a .csv file of all discharges with the following fields: database reference number, length of stay and level of care. The details of each record were verified by MBBCh V students, using a defined level-ofcare template and the full discharge summary. The data were reviewed by a senior clinician. There were 3 007 discharge summaries - 97 were not classifiable, two were test records and one was a duplicate. These 100 records were excluded. There were no primary-level records. Secondary-level patients represented 29% (854) of those discharged and 19% of total bed days. Tertiary- and quaternary-level patients together represented 71% of the total and 81% of bed days. The average length of stay was 4.31 days for secondary, 6.98 days for tertiary and 9.77 days for quaternary level-of-care allocation. Almost one-third (29%) of patients discharged from CMJAH's Department of Surgery were deemed suitable for secondarylevel care. These patients had a shorter length of stay and comprised 19% of total bed days. Students and electronic databases represent an important research resource.

Centralisation for resection of the pancreatic head: A comparison of operative factors and early outcomes during the evolving unit and tertiary unit phases at a UK institution.

PubMed

Kostalas, M; Nageswaran, H; Froghi, S; Riga, A; Kumar, R; Menezes, N; Worthington, T R; Karanjia, N D

2017-08-19

To assess impact of centralisation on patients undergoing pancreatic head resections at a tertiary hepatobiliary (HPB) centre in the UK. Data were analysed from a prospectively maintained database from 1998 to 2014 on all patients undergoing pancreatic head resections. Two specific time periods were defined; these were the evolving unit phase (EU) from 1998 to 2009 and finally the established tertiary unit phase (TU) from 2010 to 2014. Peri-operative factors and post-operative outcomes were analysed. 395 resections were undertaken during the study period. Following establishment of our tertiary HPB unit, the volume of resections undertaken increased greater than three-fold with an associated increase in case-complexity (p = 0.004). Operating time was found to increase in the TU phase compared with EU phase (p=>0.0005) whilst there was no significant difference in the rate of peri-operative transfusion, or in post-operative morbidity rates. There was a significant reduction in the post-operative length of stay in the TU phase (p = 0.003) with a significantly higher proportion of patients being discharged within 9 days of their procedure (p=<0.0005). There was also a significant reduction in 30-day post-operative mortality in the TU phase (0.5%) compared with the EU phase (3%) (p = 0.029). Data from our series of 395 cases suggests that centralisation of pancreatic cancer services to a tertiary centre does result in improved patient outcomes. The benefits of a multi-disciplinary and specialist HPB service results in a high volume, high quality unit with improved patient outcomes. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Analysis of Formant Frequencies in Patients with Oral or Oropharyngeal Cancers Treated by Glossectomy

ERIC Educational Resources Information Center

Kazi, Rehan; Prasad, Vyas M. N.; Kanagalingam, Jeeve; Georgalas, Christos; Venkitaraman, Ramachandran; Nutting, Christopher M.; Clarke, Peter; Rhys-Evans, Peter; Harrington, Kevin J.

2007-01-01

Aims: To compare voice quality as defined by formant analysis using a sustained vowel in patients who have undergone a partial glossectomy with a group of normal subjects. Methods & Procedures: The design consisted of a single centre, cross-sectional cohort study. The setting was an Adult Tertiary Referral Unit. A total of 26 patients (19…

Structural reinterpretation of the Ajo mining district, Pima County, Arizona, based on paleomagnetic and geochronologic studies.

USGS Publications Warehouse

Hagstrum, J.T.; Cox, D.P.; Miller, R.J.

1987-01-01

The Ajo mining district of southern Arizona is divided into two main structural blocks by the Gibson Arroyo fault. The eastern Camelback Mountain block contains the Late Cretaceous-early Tertiary porphyry copper deposit which has been previously thought to be associated with the displaced apex of a large intrusion exposed by deeper erosion in the western Cardigan Peak block. However, unpublished U-Pb data support a mid-Tertiary age for the western intrusion. The following sequence of mid-Tertiary events in the district are indicated: 1) emplacement of the western intrusion, 2) movement along the Gibson Arroyo fault, 3) unroofing and perhaps tilting of the pluton approx 70o to the south along with the Camelback Mountain block, 4) syntectonic depositions of the Locomotive Fanglomerate and the Ajo Volcanics, 5) continued uplift and tilting to the south totaling 40o to 60o, 6) intrusion of the youngest dikes with attendant alteration and remagnetization of the host rocks, and 7) minor (?) oblique movement along the Gibson Arroyo fault.-from Authors

Structure-Activity Relationship of the Antimalarial Ozonide Artefenomel (OZ439).

PubMed

Dong, Yuxiang; Wang, Xiaofang; Kamaraj, Sriraghavan; Bulbule, Vivek J; Chiu, Francis C K; Chollet, Jacques; Dhanasekaran, Manickam; Hein, Christopher D; Papastogiannidis, Petros; Morizzi, Julia; Shackleford, David M; Barker, Helena; Ryan, Eileen; Scheurer, Christian; Tang, Yuanqing; Zhao, Qingjie; Zhou, Lin; White, Karen L; Urwyler, Heinrich; Charman, William N; Matile, Hugues; Wittlin, Sergio; Charman, Susan A; Vennerstrom, Jonathan L

2017-04-13

Building on insights gained from the discovery of the antimalarial ozonide arterolane (OZ277), we now describe the structure-activity relationship (SAR) of the antimalarial ozonide artefenomel (OZ439). Primary and secondary amino ozonides had higher metabolic stabilities than tertiary amino ozonides, consistent with their higher pK a and lower log D 7.4 values. For primary amino ozonides, addition of polar functional groups decreased in vivo antimalarial efficacy. For secondary amino ozonides, additional functional groups had variable effects on metabolic stability and efficacy, but the most effective members of this series also had the highest log D 7.4 values. For tertiary amino ozonides, addition of polar functional groups with H-bond donors increased metabolic stability but decreased in vivo antimalarial efficacy. Primary and tertiary amino ozonides with cycloalkyl and heterocycle substructures were superior to their acyclic counterparts. The high curative efficacy of these ozonides was most often associated with high and prolonged plasma exposure, but exposure on its own did not explain the presence or absence of either curative efficacy or in vivo toxicity.

Lessons from an evolving rRNA: 16S and 23S rRNA structures from a comparative perspective

NASA Technical Reports Server (NTRS)

Gutell, R. R.; Larsen, N.; Woese, C. R.

1994-01-01

The 16S and 23S rRNA higher-order structures inferred from comparative analysis are now quite refined. The models presented here differ from their immediate predecessors only in minor detail. Thus, it is safe to assert that all of the standard secondary-structure elements in (prokaryotic) rRNAs have been identified, with approximately 90% of the individual base pairs in each molecule having independent comparative support, and that at least some of the tertiary interactions have been revealed. It is interesting to compare the rRNAs in this respect with tRNA, whose higher-order structure is known in detail from its crystal structure (36) (Table 2). It can be seen that rRNAs have as great a fraction of their sequence in established secondary-structure elements as does tRNA. However, the fact that the former show a much lower fraction of identified tertiary interactions and a greater fraction of unpaired nucleotides than the latter implies that many of the rRNA tertiary interactions remain to be located. (Alternatively, the ribosome might involve protein-rRNA rather than intramolecular rRNA interactions to stabilize three-dimensional structure.) Experimental studies on rRNA are consistent to a first approximation with the structures proposed here, confirming the basic assumption of comparative analysis, i.e., that bases whose compositions strictly covary are physically interacting. In the exhaustive study of Moazed et al. (45) on protection of the bases in the small-subunit rRNA against chemical modification, the vast majority of bases inferred to pair by covariation are found to be protected from chemical modification, both in isolated small-subunit rRNA and in the 30S subunit. The majority of the tertiary interactions are reflected in the chemical protection data as well (45). On the other hand, many of the bases not shown as paired in Fig. 1 are accessible to chemical attack (45). However, in this case a sizeable fraction of them are also protected against chemical modification (in the isolated rRNA), which suggests that considerable higher-order structure remains to be found (although all of it may not involve base-base interactions and so may not be detectable by comparative analysis). The agreement between the higher-order structure of the small-subunit rRNA and protection against chemical modification is not perfect, however; some bases shown to covary canonically are accessible to chemical modification (45).(ABSTRACT TRUNCATED AT 400 WORDS).

Thermodynamic Origins of Monovalent Facilitated RNA Folding

PubMed Central

Holmstrom, Erik D.; Fiore, Julie L.; Nesbitt, David J.

2012-01-01

Cations have long been associated with formation of native RNA structure and are commonly thought to stabilize the formation of tertiary contacts by favorably interacting with the electrostatic potential of the RNA, giving rise to an “ion atmosphere”. A significant amount of information regarding the thermodynamics of structural transitions in the presence of an ion atmosphere has accumulated and suggests stabilization is dominated by entropic terms. This work provides an analysis of how RNA–cation interactions affect the entropy and enthalpy associated with an RNA tertiary transition. Specifically, temperature-dependent single-molecule fluorescence resonance energy transfer studies have been exploited to determine the free energy (ΔG°), enthalpy (ΔH°), and entropy (ΔS°) of folding for an isolated tetraloop–receptor tertiary interaction as a function of Na+ concentration. Somewhat unexpectedly, increasing the Na+ concentration changes the folding enthalpy from a strongly exothermic process [e.g., ΔH° = −26(2) kcal/mol at 180 mM] to a weakly exothermic process [e.g., ΔH° = −4(1) kcal/mol at 630 mM]. As a direct corollary, it is the strong increase in folding entropy [Δ(ΔS°) > 0] that compensates for this loss of exothermicity for the achievement of more favorable folding [Δ(ΔG°) < 0] at higher Na+ concentrations. In conjunction with corresponding measurements of the thermodynamics of the transition state barrier, these data provide a detailed description of the folding pathway associated with the GAAA tetraloop–receptor interaction as a function of Na+ concentration. The results support a potentially universal mechanism for monovalent facilitated RNA folding, whereby an increasing monovalent concentration stabilizes tertiary structure by reducing the entropic penalty for folding. PMID:22448852

Distinct reaction pathway promoted by non-divalent-metal cations in a tertiary stabilized hammerhead ribozyme

PubMed Central

Roychowdhury-Saha, Manami; Burke, Donald H.

2007-01-01

Divalent ion sensitivity of hammerhead ribozymes is significantly reduced when the RNA structure includes appropriate tertiary stabilization. Therefore, we investigated the activity of the tertiary stabilized “RzB” hammerhead ribozyme in several nondivalent ions. Ribozyme RzB is active in spermidine and Na+ alone, although the cleavage rates are reduced by more than 1,000-fold relative to the rates observed in Mg2+ and in transition metal ions. The trivalent cobalt hexammine (CoHex) ion is often used as an exchange-inert analog of hydrated magnesium ion. Trans-cleavage rates exceeded 8 min−1 in 20 mM CoHex, which promoted cleavage through outersphere interactions. The stimulation of catalysis afforded by the tertiary structural interactions within RzB does not require Mg2+, unlike other extended hammerhead ribozymes. Site-specific interaction with at least one Mg2+ ion is suggested by CoHex competition experiments. In the presence of a constant, low concentration of Mg2+, low concentrations of CoHex decreased the rate by two to three orders of magnitude relative to the rate in Mg2+ alone. Cleavage rates increased as CoHex concentrations were raised further, but the final fraction cleaved was lower than what was observed in CoHex or Mg2+ alone. These observations suggest that Mg2+ and CoHex compete for binding and that they cause misfolded structures when they are together. The results of this study support the existence of an alternate catalytic mechanism used by nondivalent ions (especially CoHex) that is distinct from the one promoted by divalent metal ions, and they imply that divalent metals influence catalysis through a specific nonstructural role. PMID:17456566

A 'periodic table' for protein structures.

PubMed

Taylor, William R

2002-04-11

Current structural genomics programs aim systematically to determine the structures of all proteins coded in both human and other genomes, providing a complete picture of the number and variety of protein structures that exist. In the past, estimates have been made on the basis of the incomplete sample of structures currently known. These estimates have varied greatly (between 1,000 and 10,000; see for example refs 1 and 2), partly because of limited sample size but also owing to the difficulties of distinguishing one structure from another. This distinction is usually topological, based on the fold of the protein; however, in strict topological terms (neglecting to consider intra-chain cross-links), protein chains are open strings and hence are all identical. To avoid this trivial result, topologies are determined by considering secondary links in the form of intra-chain hydrogen bonds (secondary structure) and tertiary links formed by the packing of secondary structures. However, small additions to or loss of structure can make large changes to these perceived topologies and such subjective solutions are neither robust nor amenable to automation. Here I formalize both secondary and tertiary links to allow the rigorous and automatic definition of protein topology.

The geology and mechanics of formation of the Fort Rock Dome, Yavapai County, Arizona

USGS Publications Warehouse

Fuis, Gary S.

1996-01-01

The Fort Rock Dome, a craterlike structure in northern Arizona, is the erosional product of a circular domal uplift associated with a Precambrian shear zone exposed within the crater and with Tertiary volcanism. A section of Precambrian to Quaternary rocks is described, and two Tertiary units, the Crater Pasture Formation and the Fort Rock Creek Rhyodacite, are named. A mathematical model of the doming process is developed that is consistent with the history of the Fort Rock Dome.

Stratigraphic and hydrogeologic framework of the Alabama Coastal Plain

USGS Publications Warehouse

Davis, M.E.

1988-01-01

Tertiary and Cretaceous sand aquifers of the Southeastern United States Coastal Plain comprise a major multlstate aquifer system informally defined as the Southeastern Coastal Plain aquifer system, which is being studied as part of the U.S. Geological Survey's Regional Aquifer System Analysis (RASA) program. The major objectives of each RASA study are to identify, delineate, and map the distribution of permeable clastlc rock, to examine the pattern of ground-water flow within the regional aquifers, and to develop digital computer simulations to understand the flow system. The Coastal Plain aquifers in Alabama are being studied as a part of this system. This report describes the stratlgraphlc framework of the Cretaceous, Tertiary, and Quaternary Systems in Alabama to aid in delineating aquifers and confining units within the thick sequence of sediments that comprises the Southeastern Coastal Plain aquifer system in the State. Stratigraphlc units of Cretaceous and Tertiary age that make up most of the aquifer system in the Coastal Plain of Alabama consist of clastlc deposits of Early Cretaceous age; the Coker and Gordo Formations of the Tuscaloosa Group, Eutaw Formation, and Selma Group of Late Cretaceous age; and the Midway, Wilcox, and Clalborne Groups of Tertiary age. However, stratigraphlc units of late Eocene to Holocene age partially overlie and are hydraulically connected to clastic deposits in southern Alabama. These upper carbonate and clastlc stratlgraphic units also are part of the adjoining Florldan and Gulf Coastal Lowlands aquifer systems. The Coastal Plain aquifer system is underlain by pre-Cretaceous rocks consisting of low-permeabillty sedimentary rocks of Paleozolc, Triassic, and Jurassic age, and a complex of metamorphic and igneous rocks of Precambrian and Paleozolc age similar to those found near the surface in the Piedmont physiographic province. Twelve hydrogeologlc units in the Alabama Coastal Plain are defined--slx aquifers and six confining units. Aquifers of the Coastal Plain aquifer system are composed of fine to coarse sand, gravel, and limestone; confining beds are composed of clay, shale, chalk, marl, and metamorphic and igneous rocks.

Structural Biology for A-Level Students

ERIC Educational Resources Information Center

Philip, Judith

2013-01-01

The relationship between the structure and function of proteins is an important area in biochemistry. Pupils studying A-level Biology are introduced to the four levels of protein structure (primary, secondary, tertiary and quaternary) and how these can be used to describe the progressive folding of a chain of amino acid residues to a final,…

Delipidation of Cytochrome c Oxidase from Rhodobacter sphaeroides Destabilizes its Quaternary Structure

PubMed Central

Musatov, Andrej; Varhač, Rastislav; Hosler, Jonathan P.; Sedlák, Erik

2016-01-01

Delipidation of detergent-solubilized cytochrome c oxidase isolated from Rhodobacter sphaeroides (Rbs-CcO) has no apparent structural and/or functional effect on the protein, however affects its resistance against thermal or chemical denaturation. Phospholipase A2 (PLA2) hydrolysis of phospholipids that are co-purified with the enzyme removes all but two tightly bound phosphatidylethanolamines. Replacement of the removed phospholipids with nonionic detergent decreases both thermal stability of the enzyme and its resilience against the effect of chemical denaturants such as urea. In contrast to nondelipidated Rbs-CcO, the enzymatic activity of PLA2-treated Rbs-CcO is substantially diminished after exposure to high (>4M) urea concentration at room temperature without an alteration of its secondary structure. Absorbance spectroscopy and sedimentation velocity experiments revealed a strong correlation between intact tertiary structure of heme regions and quaternary structure, respectively, and the enzymatic activity of the protein. We concluded that phospholipid environment of Rbs-CcO has the protective role for stability of its tertiary and quaternary structures. PMID:26923069

A study of the thermal denaturation of the S-layer protein from Lactobacillus salivarius

NASA Astrophysics Data System (ADS)

Lighezan, Liliana; Georgieva, Ralitsa; Neagu, Adrian

2012-09-01

Surface layer (S-layer) proteins display an intrinsic self-assembly property, forming monomolecular crystalline arrays, identified in outermost structures of the cell envelope in many organisms, such as bacteria and archaea. Isolated S-layer proteins also possess the ability to recrystallize into regular lattices, being used in biotechnological applications, such as controlling the architecture of biomimetic surfaces. To this end, the stability of the S-layer proteins under high-temperature conditions is very important. In this study, the S-layer protein has been isolated from Lactobacillus salivarius 16 strain of human origin, and purified by cation-exchange chromatography. Using circular dichroism (CD) spectroscopy, we have investigated the thermal denaturation of the S-layer protein. The far- and near-UV CD spectra have been collected, and the temperature dependence of the CD signal in these spectral domains has been analyzed. The variable temperature results show that the secondary and tertiary structures of the S-layer protein change irreversibly due to the heating of the sample. After the cooling of the heated protein, the secondary and tertiary structures are partially recovered. The denaturation curves show that the protein unfolding depends on the sample concentration and on the heating rate. The secondary and tertiary structures of the protein suffer changes in the same temperature range. We have also detected an intermediate state in the protein denaturation pathway. Our results on the thermal behavior of the S-layer protein may be important for the use of S-layer proteins in biotechnological applications, as well as for a better understanding of the structure and function of S-layer proteins.

The secondary structure and the thermal unfolding parameters of the S-layer protein from Lactobacillus salivarius.

PubMed

Lighezan, Liliana; Georgieva, Ralitsa; Neagu, Adrian

2016-09-01

Surface layer (S-layer) proteins have been identified in the cell envelope of many organisms, such as bacteria and archaea. They self-assemble, forming monomolecular crystalline arrays. Isolated S-layer proteins are able to recrystallize into regular lattices, which proved useful in biotechnology. Here we investigate the structure and thermal unfolding of the S-layer protein isolated from Lactobacillus salivarius 16 strain of human origin. Using circular dichroism (CD) spectroscopy, and the software CDSSTR from DICHROWEB, CONTINLL from CDPro, as well as CDNN, we assess the fractions of the protein's secondary structural elements at temperatures ranging between 10 and 90 °C, and predict the tertiary class of the protein. To study the thermal unfolding of the protein, we analyze the temperature dependence of the CD signal in the far- and near-UV domains. Fitting the experimental data by two- and three-state models of thermal unfolding, we infer the midpoint temperatures, the temperature dependence of the changes in Gibbs free energy, enthalpy, and entropy of the unfolding transitions in standard conditions, and the temperature dependence of the equilibrium constant. We also estimate the changes in heat capacity at constant pressure in standard conditions. The results indicate that the thermal unfolding of the S-layer protein from L. salivarius is highly cooperative, since changes in the secondary and tertiary structures occur simultaneously. The thermodynamic analysis predicts a "cold" transition, at about -3 °C, of both the secondary and tertiary structures. Our findings may be important for the use of S-layer proteins in biotechnology and in biomedical applications.

The “Beta-Clasp” model of apolipoprotein A-I - a lipid-free solution structure determined by electron paramagnetic resonance spectroscopy

PubMed Central

Lagerstedt, Jens O.; Budamagunta, Madhu S.; Liu, Grace S.; DeValle, Nicole C.; Voss, John C.; Oda, Michael N.

2012-01-01

Apolipoprotein A-I (apoA-I) is the major protein component of high density lipoproteins (HDL) and plays a central role in cholesterol metabolism. The lipid-free / lipid-poor form of apoA-I is the preferred substrate for the ATP-binding cassette transporter A1 (ABCA1). The interaction of apoA-I with ABCA1 leads to the formation of cholesterol laden high density lipoprotein (HDL) particles, a key step in reverse cholesterol transport and the maintenance of cholesterol homeostasis. Knowledge of the structure of lipid-free apoA-I is essential to understanding its critical interaction with ABCA1 and the molecular mechanisms underlying HDL biogenesis. We therefore examined the structure of lipid-free apoA-I by electron paramagnetic resonance spectroscopy (EPR). Through site directed spin label EPR, we mapped the secondary structure of apoA-I and identified sites of spin coupling as residues 26, 44, 64, 167, 217 and 226. We capitalize on the fact that lipid-free apoA-I self-associates in an anti-parallel manner in solution. We employed these sites of spin coupling to define the central plane in the dimeric apoA-I complex. Applying both the constraints of dipolar coupling with the EPR-derived pattern of solvent accessibility, we assembled the secondary structure into a tertiary context, providing a solution structure for lipid-free apoA-I. PMID:22245143

Near-surface, marine seismic-reflection data defines potential hydrogeologic confinement bypass in a tertiary carbonate aquifer, southeastern Florida

USGS Publications Warehouse

Cunningham, Kevin J.; Walker, Cameron; Westcott, Richard L.

2012-01-01

Approximately 210 km of near-surface, high-frequency, marine seismic-reflection data were acquired on the southeastern part of the Florida Platform between 2007 and 2011. Many high-resolution, seismic-reflection profiles, interpretable to a depth of about 730 m, were collected on the shallow-marine shelf of southeastern Florida in water as shallow as 1 m. Landward of the present-day shelf-margin slope, these data image middle Eocene to Pleistocene strata and Paleocene to Pleistocene strata on the Miami Terrace. This high-resolution data set provides an opportunity to evaluate geologic structures that cut across confining units of the Paleocene to Oligocene-age carbonate rocks that form the Floridan aquifer system.Seismic profiles image two structural systems, tectonic faults and karst collapse structures, which breach confining beds in the Floridan aquifer system. Both structural systems may serve as pathways for vertical groundwater flow across relatively low-permeability carbonate strata that separate zones of regionally extensive high-permeability rocks in the Floridan aquifer system. The tectonic faults occur as normal and reverse faults, and collapse-related faults have normal throw. The most common fault occurrence delineated on the reflection profiles is associated with karst collapse structures. These high-frequency seismic data are providing high quality structural analogs to unprecedented depths on the southeastern Florida Platform. The analogs can be used for assessment of confinement of other carbonate aquifers and the sealing potential of deeper carbonate rocks associated with reservoirs around the world.

Discrete Haar transform and protein structure.

PubMed

Morosetti, S

1997-12-01

The discrete Haar transform of the sequence of the backbone dihedral angles (phi and psi) was performed over a set of X-ray protein structures of high resolution from the Brookhaven Protein Data Bank. Afterwards, the new dihedral angles were calculated by the inverse transform, using a growing number of Haar functions, from the lower to the higher degree. New structures were obtained using these dihedral angles, with standard values for bond lengths and angles, and with omega = 0 degree. The reconstructed structures were compared with the experimental ones, and analyzed by visual inspection and statistical analysis. When half of the Haar coefficients were used, all the reconstructed structures were not yet collapsed to a tertiary folding, but they showed yet realized most of the secondary motifs. These results indicate a substantial separation of structural information in the space of Haar transform, with the secondary structural information mainly present in the Haar coefficients of lower degrees, and the tertiary one present in the higher degree coefficients. Because of this separation, the representation of the folded structures in the space of Haar transform seems a promising candidate to encompass the problem of premature convergence in genetic algorithms.

Structural perturbation of proteins in low denaturant concentrations.

PubMed

Basak, S; Debnath, D; Haque, E; Ray, S; Chakrabarti, A

2001-01-01

The presence of very low concentrations of the widely used chemical denaturants, guanidinium chloride and urea, induce changes in the tertiary structure of proteins. We have presented results on such changes in four structurally unrelated proteins to show that such structural perturbations are common irrespective of their origin. Data representative of such structural changes are shown for the monomeric globular proteins such as horseradish peroxidase (HRP) from a plant, human serum albumin (HSA) and prothrombin from ovine blood serum, and for the membrane-associated, worm-like elongated protein, spectrin, from ovine erythrocytes. Structural alterations in these proteins were reflected in quenching studies of tryptophan fluorescence using the widely used quencher acrylamide. Stern-Volmer quenching constants measured in presence of the denaturants, even at concentrations below 100 mM, were higher than those measured in absence of the denaturants. Both steady-state and time-resolved fluorescence emission properties of tryptophan and of the extrinsic probe PRODAN were used for monitoring conformational changes in the proteins in presence of different low concentrations of the denaturants. These results are consistent with earlier studies from our laboratory indicating structural perturbations in proteins at the tertiary level, keeping their native-like secondary structure and their biological activity more or less intact.

Tertiary structure prediction and identification of druggable pocket in the cancer biomarker – Osteopontin-c

PubMed Central

2014-01-01

Background Osteopontin (Eta, secreted sialoprotein 1, opn) is secreted from different cell types including cancer cells. Three splice variant forms namely osteopontin-a, osteopontin-b and osteopontin-c have been identified. The main astonishing feature is that osteopontin-c is found to be elevated in almost all types of cancer cells. This was the vital point to consider it for sequence analysis and structure predictions which provide ample chances for prognostic, therapeutic and preventive cancer research. Methods Osteopontin-c gene sequence was determined from Breast Cancer sample and was translated to protein sequence. It was then analyzed using various software and web tools for binding pockets, docking and druggability analysis. Due to the lack of homological templates, tertiary structure was predicted using ab-initio method server – I-TASSER and was evaluated after refinement using web tools. Refined structure was compared with known bone sialoprotein electron microscopic structure and docked with CD44 for binding analysis and binding pockets were identified for drug designing. Results Signal sequence of about sixteen amino acid residues was identified using signal sequence prediction servers. Due to the absence of known structures of similar proteins, three dimensional structure of osteopontin-c was predicted using I-TASSER server. The predicted structure was refined with the help of SUMMA server and was validated using SAVES server. Molecular dynamic analysis was carried out using GROMACS software. The final model was built and was used for docking with CD44. Druggable pockets were identified using pocket energies. Conclusions The tertiary structure of osteopontin-c was predicted successfully using the ab-initio method and the predictions showed that osteopontin-c is of fibrous nature comparable to firbronectin. Docking studies showed the significant similarities of QSAET motif in the interaction of CD44 and osteopontins between the normal and splice variant forms of osteopontins and binding pockets analyses revealed several pockets which paved the way to the identification of a druggable pocket. PMID:24401206

Ab initio/GIAO-CCSD(T) (13)C NMR study of the rearrangement and dynamic aspects of rapidly equilibrating tertiary carbocations, C6H13(+) and C7H15(+).

PubMed

Olah, George A; Prakash, G K Surya; Rasul, Golam

2016-01-05

The rearrangement pathways of the equilibrating tertiary carbocations, 2,3-dimethyl-2-butyl cation (C6H13(+), 1), 2,3,3-trimethyl-2-butyl cation (C7H15(+), 5) and 2,3-dimethyl-2-pentyl cation (C7H15(+), 8 and 9) were investigated using the ab initio/GIAO-CCSD(T) (13)C NMR method. Comparing the calculated and experimental (13)C NMR chemical shifts of a series of carbocations indicates that excellent prediction of δ(13)C could be achieved through scaling. In the case of symmetrical equilibrating cations (1 and 5) the Wagner-Meerwein 1,2-hydride and 1,2-methide shifts, respectively, produce the same structure. This indicates that the overall (13)C NMR chemical shifts are conserved and independent of temperature. However, in the case of unsymmetrical equilibrating cations (8 and 9) the Wagner-Meerwein shift produces different tertiary structures, which have slightly different thermodynamic stabilities and, thus, different spectra. At the MP4(SDTQ)/cc-pVTZ//MP2/cc-pVTZ + ZPE level structure 8 is only 90 calories/mol more stable than structure 9. Based on computed (13)C NMR chemical shift calculations, mole fractions of these isomers were determined by assuming the observed chemical shifts are due to the weighted average of the chemical shifts of the static ions. © 2015 Wiley Periodicals, Inc.

Major Histopathologic Diagnoses of Chronic Wounds.

PubMed

Turi, George K; Donovan, Virginia; DiGregorio, Julie; Criscitelli, Theresa M; Kashan, Benjamin; Barrientos, Stephan; Balingcongan, Jose Ramon; Gorenstein, Scott; Brem, Harold

2016-08-01

To clarify the histopathology of acute osteomyelitis, chronic osteomyelitis, primary vasculitis, and secondary-type vasculitis. This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. After participating in this educational activity, the participant should be better able to:1. Describe the parameters and significance of this study.2. Identify chronic wound diagnosis and treatment.3. Differentiate the histopathology of osteomyelitis and vasculitis. The presence of a chronic wound can result in significant morbidity/mortality. Understanding the pathological alterations of wound tissue that are refractory to standard wound therapy is essential for effective wound management and healing. The authors describe 4 wound etiologies, specifically, acute osteomyelitis, chronic osteomyelitis, primary vasculitis, and secondary-type vasculitis. A tertiary care hospital. A retrospective review of 1392 wound operations performed during a 24-month period at a tertiary care hospital was conducted. Tissue specimens reviewed included soft tissue infections of the lower extremity, sacrum, hip/pelvis, trunk, perineum, and buttocks. Acute osteomyelitis is defined as bone tissue with a predominance of polymorphonuclear leukocytes, evidence of osteoclast bone resorption with scalloping of the cortical bone edges, and bone detritus. Chronic osteomyelitis is defined as bone tissue with a significant amount of fibrosis surrounding devitalized tissue and heavy infiltration of lymphocytes and plasma cells. Primary-type vasculitis is defined primarily as inflammation and necrosis of blood vessel walls. In cutaneous lesions of granulomatosis with polyangiitis, ulceration with numerous inflammatory granulomas is seen in the papillary dermis. Secondary vasculitis is defined by vessel wall infiltration by inflammatory cells and fibrinoid necrosis of the small vessel wall. Pathologies of these 4 types of wounds can complicate standard algorithms designed for diagnosis and treatment, and accurate diagnosis through histopathologic analysis can help tailor targeted treatment.

Analysis of gravity data beneath Endut geothermal prospect using horizontal gradient and Euler deconvolution

NASA Astrophysics Data System (ADS)

Supriyanto, Noor, T.; Suhanto, E.

2017-07-01

The Endut geothermal prospect is located in Banten Province, Indonesia. The geological setting of the area is dominated by quaternary volcanic, tertiary sediments and tertiary rock intrusion. This area has been in the preliminary study phase of geology, geochemistry, and geophysics. As one of the geophysical study, the gravity data measurement has been carried out and analyzed in order to understand geological condition especially subsurface fault structure that control the geothermal system in Endut area. After precondition applied to gravity data, the complete Bouguer anomaly have been analyzed using advanced derivatives method such as Horizontal Gradient (HG) and Euler Deconvolution (ED) to clarify the existance of fault structures. These techniques detected boundaries of body anomalies and faults structure that were compared with the lithologies in the geology map. The analysis result will be useful in making a further realistic conceptual model of the Endut geothermal area.

Protein Tertiary Structure Prediction Based on Main Chain Angle Using a Hybrid Bees Colony Optimization Algorithm

NASA Astrophysics Data System (ADS)

Mahmood, Zakaria N.; Mahmuddin, Massudi; Mahmood, Mohammed Nooraldeen

Encoding proteins of amino acid sequence to predict classified into their respective families and subfamilies is important research area. However for a given protein, knowing the exact action whether hormonal, enzymatic, transmembranal or nuclear receptors does not depend solely on amino acid sequence but on the way the amino acid thread folds as well. This study provides a prototype system that able to predict a protein tertiary structure. Several methods are used to develop and evaluate the system to produce better accuracy in protein 3D structure prediction. The Bees Optimization algorithm which inspired from the honey bees food foraging method, is used in the searching phase. In this study, the experiment is conducted on short sequence proteins that have been used by the previous researches using well-known tools. The proposed approach shows a promising result.

Rigid-Docking Approaches to Explore Protein-Protein Interaction Space.

PubMed

Matsuzaki, Yuri; Uchikoga, Nobuyuki; Ohue, Masahito; Akiyama, Yutaka

Protein-protein interactions play core roles in living cells, especially in the regulatory systems. As information on proteins has rapidly accumulated on publicly available databases, much effort has been made to obtain a better picture of protein-protein interaction networks using protein tertiary structure data. Predicting relevant interacting partners from their tertiary structure is a challenging task and computer science methods have the potential to assist with this. Protein-protein rigid docking has been utilized by several projects, docking-based approaches having the advantages that they can suggest binding poses of predicted binding partners which would help in understanding the interaction mechanisms and that comparing docking results of both non-binders and binders can lead to understanding the specificity of protein-protein interactions from structural viewpoints. In this review we focus on explaining current computational prediction methods to predict pairwise direct protein-protein interactions that form protein complexes.

Effect of structured physical activity on respiratory outcomes in sedentary elderly adults with mobility limitations

USDA-ARS?s Scientific Manuscript database

OBJECTIVES: To evaluate the effect of structured physical activity on respiratory outcomes in community dwelling elderly adults with mobility limitations. DESIGN: Multicenter, randomized trial of physical activity vs health education, with respiratory variables prespecified as tertiary outcomes over...

A Method to Predict the Structure and Stability of RNA/RNA Complexes.

PubMed

Xu, Xiaojun; Chen, Shi-Jie

2016-01-01

RNA/RNA interactions are essential for genomic RNA dimerization and regulation of gene expression. Intermolecular loop-loop base pairing is a widespread and functionally important tertiary structure motif in RNA machinery. However, computational prediction of intermolecular loop-loop base pairing is challenged by the entropy and free energy calculation due to the conformational constraint and the intermolecular interactions. In this chapter, we describe a recently developed statistical mechanics-based method for the prediction of RNA/RNA complex structures and stabilities. The method is based on the virtual bond RNA folding model (Vfold). The main emphasis in the method is placed on the evaluation of the entropy and free energy for the loops, especially tertiary kissing loops. The method also uses recursive partition function calculations and two-step screening algorithm for large, complicated structures of RNA/RNA complexes. As case studies, we use the HIV-1 Mal dimer and the siRNA/HIV-1 mutant (T4) to illustrate the method.

Importance of Diffuse Metal Ion Binding to RNA

PubMed Central

Tan, Zhi-Jie; Chen, Shi-Jie

2016-01-01

RNAs are highly charged polyanionic molecules. RNA structure and function are strongly correlated with the ionic condition of the solution. The primary focus of this article is on the role of diffusive ions in RNA folding. Due to the long-range nature of electrostatic interactions, the diffuse ions can contribute significantly to RNA structural stability and folding kinetics. We present an overview of the experimental findings as well as the theoretical developments on the diffuse ion effects in RNA folding. This review places heavy emphasis on the effect of magnesium ions. Magnesium ions play a highly efficient role in stabilizing RNA tertiary structures and promoting tertiary structural folding. The highly efficient role goes beyond the mean-field effect such as the ionic strength. In addition to the effects of specific ion binding and ion dehydration, ion-ion correlation for the diffuse ions can contribute to the efficient role of the multivalent ions such as the magnesium ions in RNA folding. PMID:22010269

Importance of diffuse metal ion binding to RNA.

PubMed

Tan, Zhi-Jie; Chen, Shi-Jie

2011-01-01

RNAs are highly charged polyanionic molecules. RNA structure and function are strongly correlated with the ionic condition of the solution. The primary focus of this article is on the role of diffusive ions in RNA folding. Due to the long-range nature of electrostatic interactions, the diffuse ions can contribute significantly to RNA structural stability and folding kinetics. We present an overview of the experimental findings as well as the theoretical developments on the diffuse ion effects in RNA folding. This review places heavy emphasis on the effect of magnesium ions. Magnesium ions play a highly efficient role in stabilizing RNA tertiary structures and promoting tertiary structural folding. The highly efficient role goes beyond the mean-field effect such as the ionic strength. In addition to the effects of specific ion binding and ion dehydration, ion-ion correlation for the diffuse ions can contribute to the efficient role of the multivalent ions such as the magnesium ions in RNA folding.

A novel assay to measure tertiary and quaternary amines in wastewater: An indicator for NDMA wastewater precursors.

PubMed

Woods-Chabane, Gwen C; Glover, Caitlin M; Marti, Erica J; Dickenson, Eric R V

2017-07-01

This study examined the potential of using a novel bulk amine assay as an approximation for the tertiary and quaternary amine load in wastewaters and surface water samples, and this approximation was compared to N-nitrosodimethylamine (NDMA) formation potential using chloramines. An existing colorimetric method was examined and optimized for the detection of amines in environmental water samples. The method consists of liquid-liquid extraction followed by a catalyzed reaction to form a yet-undefined product that is known to be both a strong chromophore and fluorophore. Previous work verified that this reaction was effectively catalyzed by a number of compounds containing tertiary and quaternary amine moieties. Many tertiary and quaternary compounds are also efficient producers of NDMA under chloramination conditions, and a linear correlation was consequently derived from the bulk amine signals vs. NDMA formation potential in various wastewater samples (R 2  = 0.74; n = 24; p-value < 0.05). The results provide evidence that approximately 2% of the tertiary and quaternary amines measured can form NDMA and an estimated 0.01-1.3% of nitrogen in dissolved organic nitrogen originates from these bulk amines. The normalization of NDMA concentration by the amine measurement revealed that ozone effectively destroyed those tertiary and quaternary amine structures more likely to form NDMA in treated wastewater samples. This bulk amine assay illustrates that proxy measurements of tertiary and quaternary amines can be linked to the NDMA formation potential of a given sample, and this approach may prove useful as a characterizing tool for NDMA precursors in wastewater. Copyright © 2017 Elsevier Ltd. All rights reserved.

RNA2D3D: a program for generating, viewing, and comparing 3-dimensional models of RNA.

PubMed

Martinez, Hugo M; Maizel, Jacob V; Shapiro, Bruce A

2008-06-01

Using primary and secondary structure information of an RNA molecule, the program RNA2D3D automatically and rapidly produces a first-order approximation of a 3-dimensional conformation consistent with this information. Applicable to structures of arbitrary branching complexity and pseudoknot content, it features efficient interactive graphical editing for the removal of any overlaps introduced by the initial generating procedure and for making conformational changes favorable to targeted features and subsequent refinement. With emphasis on fast exploration of alternative 3D conformations, one may interactively add or delete base-pairs, adjacent stems can be coaxially stacked or unstacked, single strands can be shaped to accommodate special constraints, and arbitrary subsets can be defined and manipulated as rigid bodies. Compaction, whereby base stacking within stems is optimally extended into connecting single strands, is also available as a means of strategically making the structures more compact and revealing folding motifs. Subsequent refinement of the first-order approximation, of modifications, and for the imposing of tertiary constraints is assisted with standard energy refinement techniques. Previously determined coordinates for any part of the molecule are readily incorporated, and any part of the modeled structure can be output as a PDB or XYZ file. Illustrative applications in the areas of ribozymes, viral kissing loops, viral internal ribosome entry sites, and nanobiology are presented.

An investigation of extensional tectonics of southern California

NASA Technical Reports Server (NTRS)

Richard, Steven M.; Crowell, John C.

1992-01-01

Geologic mapping and interpretation of Landsat TM imagery has filled in a significant gap in the geologic database for southwestern Arizona and southeastern California. The new data acquired, along with interpretation of existing data, forms the basis for a proposed reconstruction of late Tertiary faults in these regions. This reconstruction integrates available geological and geophysical data to define the eastern limit of deformation related to the San Andreas fault, and has significant implications for other recently proposed reconstructions of Tertiary deformation in the region. This progress in interpreting deformation during the last 10 Ma in the region forms a foundation for developing and testing models of older deformation in this region, including the initiation of San Andreas fault system, and the interaction of Early Miocene extension in the Basin and Range with the evolving San Andreas system.

Blast-Induced Acceleration in a Shock Tube: Distinguishing Primary and Tertiary Blast Injury

DTIC Science & Technology

2015-10-01

these well-defined exposure conditions, anesthetized rats are used to simultaneously record intracranial pressure (ICP), intravascular pressure , and...blast flow conditions (e.g. peak static and total pressure , positive phase duration, and impulse) and acceleration and displacement of a wide range of...resultant pressure responses in varied compartments in concert with the neuropathological, neurochemical, and neurobehavioral consequences of exposures

Project Based Learning (PBL) and Webquest: New Dimensions in Achieving Learner Autonomy in a Class at Tertiary Level

ERIC Educational Resources Information Center

Akhand, Mohd. Moniruzzaman

2015-01-01

Now a day, the buzz word for a language classroom is "learner autonomy" that is defined differently by different experts. The fundamental of learner autonomy, however, is to involve the learning in the teaching and learning process. The term "webquest" is also a new concept to the teachers in this part of the world. A webquest…

The Concept of Proportionality as a Predictor of Success at the University of Papua and New Guinea. E.R.U. Report 6.

ERIC Educational Resources Information Center

Jones, John

A main problem encountered by science and mathematics students at secondary and tertiary institutions throughout Papua New Guinea is that of dealing with ratio and proportion. The problem is most clearly defined in science, since this is the area in which the quantitative manipulation of physical variables is most frequently carried out. An…

Ligand-mediated and tertiary interactions cooperatively stabilize the P1 region in the guanine-sensing riboswitch

PubMed Central

Hanke, Christian A.

2017-01-01

Riboswitches are genetic regulatory elements that control gene expression depending on ligand binding. The guanine-sensing riboswitch (Gsw) binds ligands at a three-way junction formed by paired regions P1, P2, and P3. Loops L2 and L3 cap the P2 and P3 helices and form tertiary interactions. Part of P1 belongs to the switching sequence dictating the fate of the mRNA. Previous studies revealed an intricate relationship between ligand binding and presence of the tertiary interactions, and between ligand binding and influence on the P1 region. However, no information is available on the interplay among these three main regions in Gsw. Here we show that stabilization of the L2-L3 region by tertiary interactions, and the ligand binding site by ligand binding, cooperatively influences the structural stability of terminal base pairs in the P1 region in the presence of Mg2+ ions. The results are based on molecular dynamics simulations with an aggregate simulation time of ~10 μs across multiple systems of the unbound state of the Gsw aptamer and a G37A/C61U mutant, and rigidity analyses. The results could explain why the three-way junction is a central structural element also in other riboswitches and how the cooperative effect could become contextual with respect to intracellular Mg2+ concentration. The results suggest that the transmission of allosteric information to P1 can be entropy-dominated. PMID:28640851

Novel recombinant insulin analogue with flexible C-terminus in B chain. NMR structure of biosynthetic engineered A22G-B31K-B32R human insulin monomer in water/acetonitrile solution.

PubMed

Borowicz, Piotr; Bocian, Wojciech; Sitkowski, Jerzy; Bednarek, Elżbieta; Mikiewicz-Syguła, Diana; Błażej-Sosnowska, Sylwia; Bogiel, Monika; Rusek, Dorota; Kurzynoga, Dariusz; Kozerski, Lech

2011-11-01

A tertiary structure of recombinant A22(G)-B31(K)-B32(R)-human insulin monomer (insulin GKR) has been characterized by (1)H, (13)C NMR at natural isotopic abundance using NOESY, TOCSY, (1)H/(13)C-GHSQC, and (1)H/(13)C-GHSQC-TOCSY spectra. Translational diffusion studies indicate the monomer structure in water/acetonitrile (65/35vol.%). CSI analysis confirms existence of secondary structure motifs present in human insulin standard (HIS). Both techniques allow to establish that in this solvent recombinant insulin GKR exists as a monomer. Starting from structures calculated by the program CYANA, two different refinement protocols used molecular dynamics simulated annealing with the program AMBER; in vacuum (AMBER_VC), and including a generalized Born solvent model (AMBER_GB). From these calculations an ensemble of 20 structures of lowest energy was chosen which represents the tertiary structure of studied insulin. Here we present novel insulin with added A22(G) amino acid which interacts with β-turn environment resulting in high flexibility of B chain C-terminus. Copyright © 2011 Elsevier B.V. All rights reserved.

Consistent global structures of complex RNA states through multidimensional chemical mapping

PubMed Central

Cheng, Clarence Yu; Chou, Fang-Chieh; Kladwang, Wipapat; Tian, Siqi; Cordero, Pablo; Das, Rhiju

2015-01-01

Accelerating discoveries of non-coding RNA (ncRNA) in myriad biological processes pose major challenges to structural and functional analysis. Despite progress in secondary structure modeling, high-throughput methods have generally failed to determine ncRNA tertiary structures, even at the 1-nm resolution that enables visualization of how helices and functional motifs are positioned in three dimensions. We report that integrating a new method called MOHCA-seq (Multiplexed •OH Cleavage Analysis with paired-end sequencing) with mutate-and-map secondary structure inference guides Rosetta 3D modeling to consistent 1-nm accuracy for intricately folded ncRNAs with lengths up to 188 nucleotides, including a blind RNA-puzzle challenge, the lariat-capping ribozyme. This multidimensional chemical mapping (MCM) pipeline resolves unexpected tertiary proximities for cyclic-di-GMP, glycine, and adenosylcobalamin riboswitch aptamers without their ligands and a loose structure for the recently discovered human HoxA9D internal ribosome entry site regulon. MCM offers a sequencing-based route to uncovering ncRNA 3D structure, applicable to functionally important but potentially heterogeneous states. DOI: http://dx.doi.org/10.7554/eLife.07600.001 PMID:26035425

Universal partitioning of the hierarchical fold network of 50-residue segments in proteins

PubMed Central

Ito, Jun-ichi; Sonobe, Yuki; Ikeda, Kazuyoshi; Tomii, Kentaro; Higo, Junichi

2009-01-01

Background Several studies have demonstrated that protein fold space is structured hierarchically and that power-law statistics are satisfied in relation between the numbers of protein families and protein folds (or superfamilies). We examined the internal structure and statistics in the fold space of 50 amino-acid residue segments taken from various protein folds. We used inter-residue contact patterns to measure the tertiary structural similarity among segments. Using this similarity measure, the segments were classified into a number (Kc) of clusters. We examined various Kc values for the clustering. The special resolution to differentiate the segment tertiary structures increases with increasing Kc. Furthermore, we constructed networks by linking structurally similar clusters. Results The network was partitioned persistently into four regions for Kc ≥ 1000. This main partitioning is consistent with results of earlier studies, where similar partitioning was reported in classifying protein domain structures. Furthermore, the network was partitioned naturally into several dozens of sub-networks (i.e., communities). Therefore, intra-sub-network clusters were mutually connected with numerous links, although inter-sub-network ones were rarely done with few links. For Kc ≥ 1000, the major sub-networks were about 40; the contents of the major sub-networks were conserved. This sub-partitioning is a novel finding, suggesting that the network is structured hierarchically: Segments construct a cluster, clusters form a sub-network, and sub-networks constitute a region. Additionally, the network was characterized by non-power-law statistics, which is also a novel finding. Conclusion Main findings are: (1) The universe of 50 residue segments found here was characterized by non-power-law statistics. Therefore, the universe differs from those ever reported for the protein domains. (2) The 50-residue segments were partitioned persistently and universally into some dozens (ca. 40) of major sub-networks, irrespective of the number of clusters. (3) These major sub-networks encompassed 90% of all segments. Consequently, the protein tertiary structure is constructed using the dozens of elements (sub-networks). PMID:19454039

Stability of Secondary and Tertiary Structures of Virus-Like Particles Representing Noroviruses: Effects of pH, Ionic Strength, and Temperature and Implications for Adhesion to Surfaces.

PubMed

Samandoulgou, Idrissa; Hammami, Riadh; Morales Rayas, Rocio; Fliss, Ismail; Jean, Julie

2015-11-01

Loss of ordered molecular structure in proteins is known to increase their adhesion to surfaces. The aim of this work was to study the stability of norovirus secondary and tertiary structures and its implications for viral adhesion to fresh foods and agrifood surfaces. The pH, ionic strength, and temperature conditions studied correspond to those prevalent in the principal vehicles of viral transmission (vomit and feces) and in the food processing and handling environment (pasteurization and refrigeration). The structures of virus-like particles representing GI.1, GII.4, and feline calicivirus (FCV) were studied using circular dichroism and intrinsic UV fluorescence. The particles were remarkably stable under most of the conditions. However, heating to 65°C caused losses of β-strand structure, notably in GI.1 and FCV, while at 75°C the α-helix content of GII.4 and FCV decreased and tertiary structures unfolded in all three cases. Combining temperature with pH or ionic strength caused variable losses of structure depending on the particle type. Regardless of pH, heating to pasteurization temperatures or higher would be required to increase GII.4 and FCV adhesion, while either low or high temperatures would favor GI.1 adhesion. Regardless of temperature, increased ionic strength would increase GII.4 adhesion but would decrease GI.1 adhesion. FCV adsorption would be greater at refrigeration, pasteurization, or high temperature combined with a low salt concentration or at a higher NaCl concentration regardless of temperature. Norovirus adhesion mediated by hydrophobic interaction may depend on hydrophobic residues normally exposed on the capsid surface at pH 3, pH 8, physiological ionic strength, and low temperature, while at pasteurization temperatures it may rely more on buried hydrophobic residues exposed upon structural rearrangement. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Geochronology and correlation of Tertiary volcanic and intrusive rocks in part of the southern Toquima Range, Nye County, Nevada

USGS Publications Warehouse

Shawe, Daniel R.; Snee, Lawrence W.; Byers, Frank M.; du Bray, Edward A.

2014-01-01

Extensive volcanic and intrusive igneous activity, partly localized along regional structural zones, characterized the southern Toquima Range, Nevada, in the late Eocene, Oligocene, and Miocene. The general chronology of igneous activity has been defined previously. This major episode of Tertiary magmatism began with emplacement of a variety of intrusive rocks, followed by formation of nine major calderas and associated with voluminous extrusive and additional intrusive activity. Emplacement of volcanic eruptive and collapse megabreccias accompanied formation of some calderas. Penecontemporaneous volcanism in central Nevada resulted in deposition of distally derived outflow facies ash-flow tuff units that are interleaved in the Toquima Range with proximally derived ash-flow tuffs. Eruption of the Northumberland Tuff in the north part of the southern Toquima Range and collapse of the Northumberland caldera occurred about 32.3 million years ago. The poorly defined Corcoran Canyon caldera farther to the southeast formed following eruption of the tuff of Corcoran Canyon about 27.2 million years ago. The Big Ten Peak caldera in the south part of the southern Toquima Range Tertiary volcanic complex formed about 27 million years ago during eruption of the tuff of Big Ten Peak and associated air-fall tuffs. The inferred Ryecroft Canyon caldera formed in the south end of the Monitor Valley adjacent to the southern Toquima Range and just north of the Big Ten Peak caldera in response to eruption of the tuff of Ryecroft Canyon about 27 million years ago, and the Moores Creek caldera just south of the Northumberland caldera developed at about the same time. Eruption of the tuff of Mount Jefferson about 26.8 million years ago was accompanied by collapse of the Mount Jefferson caldera in the central part of the southern Toquima Range. An inferred caldera, mostly buried beneath alluvium of Big Smoky Valley southwest of the Mount Jefferson caldera, formed about 26.5 million years ago with eruption of the tuff of Round Mountain. The Manhattan caldera south of the Mount Jefferson caldera and northwest of the Big Ten Peak caldera formed in association with eruption of a series of tuffs, principally the Round Rock Formation, mostly ash-flow tuff, about 24.4 million years ago. Extensive 40Ar/39Ar dating of about 60 samples that represent many of the Tertiary extrusive and intrusive rocks in the southern Toquima Range provides precise ages that refine the chronology of previously dated units. New geochronologic data indicate that the petrogenetically related Corcoran Canyon, Ryecroft Canyon, and Mount Jefferson calderas formed during a period of about 560,000 years. Electron microprobe analyses of phenocrysts from 20 samples of six dated units underscore inferred petrogenetic relations among some of these units. In particular, compositions of augite, hornblende, and biotite in tuffs erupted from the Corcoran Canyon, Ryecroft Canyon, and Mount Jefferson calderas are similar, which suggests that magmas represented by these tuffs have similar petrogenetic histories. The unique occurrence of hypersthene in Isom-type tuff confirms its derivation from a source beyond the southern Toquima Range.

Publications - RI 2000-1A | Alaska Division of Geological & Geophysical

Science.gov Websites

; Folding; Formations; Fossils; Generalized; Geologic; Geologic Map; Geology; Geomorphology; Glacial ; Silt; Structure; Surficial; Surficial Geology; Tectonics; Tertiary; Thaw Lakes; Trace Fossils

Acetoacetate promotes the formation of fluorescent advanced glycation end products (AGEs).

PubMed

Bohlooli, Mousa; Ghaffari-Moghaddam, Mansour; Khajeh, Mostafa; Aghashiri, Zohre; Sheibani, Nader; Moosavi-Movahedi, Ali Akbar

2016-12-01

Acetoacetate (AA) is an important ketone body, which produces reactive oxygen species (ROS). Advanced glycation end products (AGEs) are defined as final products of glycation process whose production is influenced by the levels of ROS. The accumulation of AGEs in the body contributes to pathogenesis of many diseases including complications of diabetes, and Alzheimer's and Parkinson's disease. Here, we evaluated the impact of AA on production of AGEs upon incubation of human serum albumin (HSA) with glucose. The effect of AA on the AGEs formation of HSA was studied under physiological conditions after incubation with glucose for 35 days. The physical techniques including circular dichroism (CD) and fluorescence spectroscopy were used to assess the impact of AA on formation and structural changes of glycated HSA (GHSA). Our results indicated that the secondary and tertiary structural changes of GHSA were increased in the presence of AA. The fluorescence intensity measurements of AGEs also showed an increase in AGEs formation. Acetoacetate has an activator effect in formation of AGEs through ROS production. The presence of AA may result in enhanced glycation in the presence of glucose and severity of complications associated with accumulation of AGEs.

α-Helical Structural Elements within the Voltage-Sensing Domains of a K+ Channel

PubMed Central

Li-Smerin, Yingying; Hackos, David H.; Swartz, Kenton J.

2000-01-01

Voltage-gated K+ channels are tetramers with each subunit containing six (S1–S6) putative membrane spanning segments. The fifth through sixth transmembrane segments (S5–S6) from each of four subunits assemble to form a central pore domain. A growing body of evidence suggests that the first four segments (S1–S4) comprise a domain-like voltage-sensing structure. While the topology of this region is reasonably well defined, the secondary and tertiary structures of these transmembrane segments are not. To explore the secondary structure of the voltage-sensing domains, we used alanine-scanning mutagenesis through the region encompassing the first four transmembrane segments in the drk1 voltage-gated K+ channel. We examined the mutation-induced perturbation in gating free energy for periodicity characteristic of α-helices. Our results are consistent with at least portions of S1, S2, S3, and S4 adopting α-helical secondary structure. In addition, both the S1–S2 and S3–S4 linkers exhibited substantial helical character. The distribution of gating perturbations for S1 and S2 suggest that these two helices interact primarily with two environments. In contrast, the distribution of perturbations for S3 and S4 were more complex, suggesting that the latter two helices make more extensive protein contacts, possibly interfacing directly with the shell of the pore domain. PMID:10613917

Modulation of cardiac myocyte phenotype in vitro by the composition and orientation of the extracellular matrix.

PubMed

Simpson, D G; Terracio, L; Terracio, M; Price, R L; Turner, D C; Borg, T K

1994-10-01

Cellular phenotype is the result of a dynamic interaction between a cell's intrinsic genetic program and the morphogenetic signals that serve to modulate the extent to which that program is expressed. In the present study we have examined how morphogenetic information might be stored in the extracellular matrix (ECM) and communicated to the neonatal heart cell (NHC) by the cardiac alpha 1 beta 1 integrin molecule. A thin film of type I collagen (T1C) was prepared with a defined orientation. This was achieved by applying T1C to the peripheral edge of a 100 mm culture dish. The T1C was then drawn across the surface of the dish in a continuous stroke with a sterile cell scraper and allowed to polymerize. When NHCs were cultured on this substrate, they spread, as a population, along a common axis in parallel with the gel lattice and expressed an in vivo-like phenotype. Individual NHCs displayed an elongated, rod-like shape and disclosed parallel arrays of myofibrils. These phenotypic characteristics were maintained for at least 4 weeks in primary culture. The evolution of this tissue-like organizational pattern was dependent upon specific interactions between the NHCs and the collagen-based matrix that were mediated by the cardiac alpha 1 beta 1 integrin complex. This conclusion was supported by a variety of experimental results. Altering the tertiary structure of the matrix or blocking the extracellular domains of either the cardiac alpha 1 or beta 1 integrin chain inhibited the expression of the tissue-like pattern of organization. Neither cell-to-cell contact or contractile function were necessary to induce the formation of the rod-like cell shape. However, beating activity was necessary for the assembly of a well-differentiated myofibrillar apparatus. These data suggest that the cardiac alpha 1 beta 1 integrin complex serves to detect and transduce phenotypic information stored within the tertiary structure of the surrounding matrix.

Chemoselective SN2' Allylations of Detrifluoroacetylatively In Situ Generated 3-Fluoroindolin-2-one-Derived Tertiary Enolates with Morita-Baylis-Hillman Carbonates.

PubMed

Zhu, Yi; Mei, Haibo; Han, Jianlin; Soloshonok, Vadim A; Zhou, Jie; Pan, Yi

2017-12-15

The first example of the S N 2' reaction type of the detrifluoroacetylatively in situ generated tertiary fluoro-enolates in the uncatalyzed reactions with Morita-Baylis-Hillman derivatives has been described. The S N 2' substitution takes place in a highly chemoselective manner as no corresponding S N 2 products were observed in the reaction mixtures. Due to the excellent stereochemical outcome, the reactions seem to have an apparent synthetic value for the preparation of structurally new fluorinated oxindoles.

Geophysical interpretations west of and within the northwestern part of the Nevada Test Site

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

Grauch, V.J.; Sawyer, D.A.; Fridrich, C.J.

1997-12-31

This report focuses on interpretation of gravity and new magnetic data west of the Nevada Test Site (NTS) and within the northwestern part of NTS. The interpretations integrate the gravity and magnetic data with other geophysical, geological, and rock property data to put constraints on tectonic and magmatic features not exposed at the surface. West of NTS, where drill hole information is absent, these geophysical data provide the best available information on the subsurface. Interpreted subsurface features include calderas, intrusions, basalt flows and volcanoes, Tertiary basins, structurally high pre-Tertiary rocks, and fault zones. New features revealed by this study includemore » (1) a north-south buried tectonic fault east of Oasis Mountain, which the authors call the Hogback fault; (2) an east striking fault or accommodation zone along the south side of Oasis Valley basin, which they call the Hot Springs fault; (3) a NNE striking structural zone coinciding with the western margins of the caldera complexes; (4) regional magnetic highs that probably represent a thick sequence of Tertiary volcanic rocks; and (5) two probable buried calderas that may be related to the tuffs of Tolicha Peak and of Sleeping Butte, respectively.« less

Evidence for close side-chain packing in an early protein folding intermediate previously assumed to be a molten globule

PubMed Central

Rosen, Laura E.; Connell, Katelyn B.; Marqusee, Susan

2014-01-01

The molten globule, a conformational ensemble with significant secondary structure but only loosely packed tertiary structure, has been suggested to be a ubiquitous intermediate in protein folding. However, it is difficult to assess the tertiary packing of transiently populated species to evaluate this hypothesis. Escherichia coli RNase H is known to populate an intermediate before the rate-limiting barrier to folding that has long been thought to be a molten globule. We investigated this hypothesis by making mimics of the intermediate that are the ground-state conformation at equilibrium, using two approaches: a truncation to generate a fragment mimic of the intermediate, and selective destabilization of the native state using point mutations. Spectroscopic characterization and the response of the mimics to further mutation are consistent with studies on the transient kinetic intermediate, indicating that they model the early intermediate. Both mimics fold cooperatively and exhibit NMR spectra indicative of a closely packed conformation, in contrast to the hypothesis of molten tertiary packing. This result is important for understanding the nature of the subsequent rate-limiting barrier to folding and has implications for the assumption that many other proteins populate molten globule folding intermediates. PMID:25258414

Evidence for close side-chain packing in an early protein folding intermediate previously assumed to be a molten globule.

PubMed

Rosen, Laura E; Connell, Katelyn B; Marqusee, Susan

2014-10-14

The molten globule, a conformational ensemble with significant secondary structure but only loosely packed tertiary structure, has been suggested to be a ubiquitous intermediate in protein folding. However, it is difficult to assess the tertiary packing of transiently populated species to evaluate this hypothesis. Escherichia coli RNase H is known to populate an intermediate before the rate-limiting barrier to folding that has long been thought to be a molten globule. We investigated this hypothesis by making mimics of the intermediate that are the ground-state conformation at equilibrium, using two approaches: a truncation to generate a fragment mimic of the intermediate, and selective destabilization of the native state using point mutations. Spectroscopic characterization and the response of the mimics to further mutation are consistent with studies on the transient kinetic intermediate, indicating that they model the early intermediate. Both mimics fold cooperatively and exhibit NMR spectra indicative of a closely packed conformation, in contrast to the hypothesis of molten tertiary packing. This result is important for understanding the nature of the subsequent rate-limiting barrier to folding and has implications for the assumption that many other proteins populate molten globule folding intermediates.

Group 6 metal pentacarbonyl complexes of air-stable primary, secondary, and tertiary ferrocenylethylphosphines.

PubMed

Rabiee Kenaree, Amir; Sauvé, Ethan R; Ragogna, Paul J; Gilroy, Joe B

2016-02-21

The synthesis and characterization of a series of Group 6 metal pentacarbonyl complexes of air stable primary, secondary, and tertiary phosphines containing ferrocenylethyl substituents are reported [M(CO)5L: M = Cr, Mo, W; L = PH2(CH2CH2Fc), PH(CH2CH2Fc)2, P(CH2CH2Fc)3]. The structure and composition of the complexes were confirmed by multinuclear NMR spectroscopy, IR and UV-Vis absorption spectroscopy, mass spectrometry, X-ray crystallography, and elemental analysis. The solid-state structural data reported revealed trends in M-C and M-P bond lengths that mirrored those of the atomic radii of the Group 6 metals involved. UV-Vis absorption spectroscopy and cyclic voltammetry highlighted characteristics consistent with electronically isolated ferrocene units including wavelengths of maximum absorption between 435 and 441 nm and reversible one-electron (per ferrocene unit) oxidation waves between 10 and -5 mV relative to the ferrocene/ferrocenium redox couple. IR spectroscopy confirmed that the σ donating ability of the phosphines increased as ferrocenylethyl substituents were introduced and that the tertiary phosphine ligand described is a stronger σ donor than PPh3 and a weaker σ donor than PEt3, respectively.

Model for an RNA tertiary interaction from the structure of an intermolecular complex between a GAAA tetraloop and an RNA helix.

PubMed

Pley, H W; Flaherty, K M; McKay, D B

1994-11-03

In large structured RNAs, RNA hairpins in which the strands of the duplex stem are connected by a tetraloop of the consensus sequence 5'-GNRA (where N is any nucleotide, and R is either G or A) are unusually frequent. In group I introns there is a covariation in sequence between nucleotides in the third and fourth positions of the loop with specific distant base pairs in putative RNA duplex stems: GNAA loops correlate with successive 5'-C-C.G-C base pairs in stems, whereas GNGA loops correlate with 5'-C-U.G-A. This has led to the suggestion that GNRA tetraloops may be involved in specific long-range tertiary interactions, with each A in position 3 or 4 of the loop interacting with a C-G base pair in the duplex, and G in position 3 interacting with a U-A base pair. This idea is supported experimentally for the GAAA loop of the P5b extension of the group I intron of Tetrahymena thermophila and the L9 GUGA terminal loop of the td intron of bacteriophage T4 (ref. 4). NMR has revealed the overall structure of the tetraloop for 12-nucleotide hairpins with GCAA and GAAA loops and models have been proposed for the interaction of GNRA tetraloops with base pairs in the minor groove of A-form RNA. Here we describe the crystal structure of an intermolecular complex between a GAAA tetraloop and an RNA helix. The interactions we observe correlate with the specificity of GNRA tetraloops inferred from phylogenetic studies, suggesting that this complex is a legitimate model for intramolecular tertiary interactions mediated by GNRA tetraloops in large structured RNAs.

Molecular modelling of the Norrie disease protein predicts a cystine knot growth factor tertiary structure.

PubMed

Meitinger, T; Meindl, A; Bork, P; Rost, B; Sander, C; Haasemann, M; Murken, J

1993-12-01

The X-lined gene for Norrie disease, which is characterized by blindness, deafness and mental retardation has been cloned recently. This gene has been thought to code for a putative extracellular factor; its predicted amino acid sequence is homologous to the C-terminal domain of diverse extracellular proteins. Sequence pattern searches and three-dimensional modelling now suggest that the Norrie disease protein (NDP) has a tertiary structure similar to that of transforming growth factor beta (TGF beta). Our model identifies NDP as a member of an emerging family of growth factors containing a cystine knot motif, with direct implications for the physiological role of NDP. The model also sheds light on sequence related domains such as the C-terminal domain of mucins and of von Willebrand factor.

Progress Report on Alloy 617 Time Dependent Allowables

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

Wright, Julie Knibloe

2015-06-01

Time dependent allowable stresses are required in the ASME Boiler and Pressure Vessel Code for design of components in the temperature range where time dependent deformation (i.e., creep) is expected to become significant. There are time dependent allowable stresses in Section IID of the Code for use in the non-nuclear construction codes, however, there are additional criteria that must be considered in developing time dependent allowables for nuclear components. These criteria are specified in Section III NH. St is defined as the lesser of three quantities: 100% of the average stress required to obtain a total (elastic, plastic, primary andmore » secondary creep) strain of 1%; 67% of the minimum stress to cause rupture; and 80% of the minimum stress to cause the initiation of tertiary creep. The values are reported for a range of temperatures and for time increments up to 100,000 hours. These values are determined from uniaxial creep tests, which involve the elevated temperature application of a constant load which is relatively small, resulting in deformation over a long time period prior to rupture. The stress which is the minimum resulting from these criteria is the time dependent allowable stress St. In this report data from a large number of creep and creep-rupture tests on Alloy 617 are analyzed using the ASME Section III NH criteria. Data which are used in the analysis are from the ongoing DOE sponsored high temperature materials program, form Korea Atomic Energy Institute through the Generation IV VHTR Materials Program and historical data from previous HTR research and vendor data generated in developing the alloy. It is found that the tertiary creep criterion determines St at highest temperatures, while the stress to cause 1% total strain controls at low temperatures. The ASME Section III Working Group on Allowable Stress Criteria has recommended that the uncertainties associated with determining the onset of tertiary creep and the lack of significant cavitation associated with early tertiary creep strain suggest that the tertiary creep criteria is not appropriate for this material. If the tertiary creep criterion is dropped from consideration, the stress to rupture criteria determines St at all but the lowest temperatures.« less

"Actually, I 'May' Be Clever Enough to Do It". Using Identity as a Lens to Investigate Students' Trajectories towards Science and University

ERIC Educational Resources Information Center

Krogh, Lars Brian; Andersen, Hanne Moeller

2013-01-01

We have followed a group of students in the potential pipeline for science through their last years of upper secondary school and in the context of a university mentorship program. The student group is defined by their choice of Mathematics at A-level which is mandatory for admission to tertiary STEM education in Denmark. Rich data (repeated…

[Improving inpatient pharmacoterapeutic process by Lean Six Sigma methodology].

PubMed

Font Noguera, I; Fernández Megía, M J; Ferrer Riquelme, A J; Balasch I Parisi, S; Edo Solsona, M D; Poveda Andres, J L

2013-01-01

Lean Six Sigma methodology has been used to improve care processes, eliminate waste, reduce costs, and increase patient satisfaction. To analyse the results obtained with Lean Six Sigma methodology in the diagnosis and improvement of the inpatient pharmacotherapy process during structural and organisational changes in a tertiary hospital. 1.000 beds tertiary hospital. prospective observational study. The define, measure, analyse, improve and control (DMAIC), were deployed from March to September 2011. An Initial Project Charter was updated as results were obtained. 131 patients with treatments prescribed within 24h after admission and with 4 drugs. safety indicators (medication errors), and efficiency indicators (complaints and time delays). Proportion of patients with a medication error was reduced from 61.0% (25/41 patients) to 55.7% (39/70 patients) in four months. Percentage of errors (regarding the opportunities for error) decreased in the different phases of the process: Prescription: from 5.1% (19/372 opportunities) to 3.3% (19/572 opportunities); Preparation: from 2.7% (14/525 opportunities) to 1.3% (11/847 opportunities); and administration: from 4.9% (16/329 opportunities) to 3.0% (13/433 opportunities). Nursing complaints decreased from 10.0% (2119/21038 patients) to 5.7% (1779/31097 patients). The estimated economic impact was 76,800 euros saved. An improvement in the pharmacotherapeutic process and a positive economic impact was observed, as well as enhancing patient safety and efficiency of the organization. Standardisation and professional training are future Lean Six Sigma candidate projects. Copyright © 2012 SECA. Published by Elsevier Espana. All rights reserved.

Syntheses of conformationally defined analogues of tyramine and phenylethanolamine and their biological evaluations at central dopamine receptors and the active site of phenylethanolamine N-methyltransferase

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

Ye, Q.

Tyramine analogues 31-33 and 37-39 were evaluated for dopaminergic activities on rat striatal tissues with radioligands ({sup 3}H)SCH23390 for D-1 receptor and ({sup 3}H)spiroperidol for D-2 receptor. The tertiary amines 37-39 were generally more potent than the primary amines 31-33. In the primary amines, 33 (2-OH) was more potent than 31 and 32, and in the tertiary amines, 37 (4-OH) was more potent than 38 and 39 at both D-1 and D-2 receptors. The reduced activity of 31-33 and 37-39 compared with corresponding hydroxyl-substituted 2ATs is consistent with a negative interaction from the extra ethano bridge in their binding tomore » the dopamine receptors. No selectivity was observed in both these conformationally defined tyramines (31-33 and 37-39) and conformationally restricted tyramines; a good correlation was observed between log IC{sub 5}O values at D-1 and D-2 receptors. The tyramines 31-33, the phenylethanolamines 45 and 46, and the phenylethylamine 44 (X, Y = H) were evaluated for activities as either substrates or inhibitors of phenylethanolamine N-methyltransferase (PNMT) by an in vitro radiochemical assay.« less

Structural insights into a key carotenogenesis related enzyme phytoene synthase of P. falciparum: a novel drug target for malaria.

PubMed

Agarwal, Shalini; Sharma, Vijeta; Phulera, Swastik; Abdin, M Z; Ayana, R; Singh, Shailja

2015-12-01

Carotenoids represent a diverse group of pigments derived from the common isoprenoid precursors and fulfill a variety of critical functions in plants and animals. Phytoene synthase (PSY), a transferase enzyme that catalyzes the first specific step in carotenoid biosynthesis plays a central role in the regulation of a number of essential functions mediated via carotenoids. PSYs have been deeply investigated in plants, bacteria and algae however in apicomplexans it is poorly studied. In an effort to characterize PSY in apicomplexans especially the malaria parasite Plasmodium falciparum (P. falciparum), a detailed bioinformatics analysis is undertaken. We have analysed the Phylogenetic relationship of PSY also referred to as octaprenyl pyrophosphate synthase (OPPS) in P. falciparum with other taxonomic groups. Further, we in silico characterized the secondary and tertiary structures of P. falciparum PSY/OPPS and compared the tertiary structures with crystal structure of Thermotoga maritima (T. maritima) OPPS. Our results evidenced the resemblance of P. falciparum PSY with the active site of T. maritima OPPS. Interestingly, the comparative structural analysis revealed an unconserved unique loop in P. falciparum OPPS/PSY. Such structural insights might contribute novel accessory functions to the protein thus, offering potential drug targets.

Contributions of historical and contemporary geographic and environmental factors to phylogeographic structure in a Tertiary relict species, Emmenopterys henryi (Rubiaceae)

PubMed Central

Zhang, Yong-Hua; Wang, Ian J.; Comes, Hans Peter; Peng, Hua; Qiu, Ying-Xiong

2016-01-01

Examining how historical and contemporary geographic and environmental factors contribute to genetic divergence at different evolutionary scales is a central yet largely unexplored question in ecology and evolution. Here, we examine this key question by investigating how environmental and geographic factors across different epochs have driven genetic divergence at deeper (phylogeographic) and shallower (landscape genetic) evolutionary scales in the Chinese Tertiary relict tree Emmenopterys henryi. We found that geography played a predominant role at all levels – phylogeographic clades are broadly geographically structured, the deepest levels of divergence are associated with major geological or pre-Quaternary climatic events, and isolation by distance (IBD) primarily explained population genetic structure. However, environmental factors are clearly also important – climatic fluctuations since the Last Interglacial (LIG) have likely contributed to phylogeographic structure, and the population genetic structure (in our AFLP dataset) was partly explained by isolation by environment (IBE), which may have resulted from natural selection in environments with divergent climates. Thus, historical and contemporary geography and historical and contemporary environments have all shaped patterns of genetic structure in E. henryi, and, in fact, changes in the landscape through time have also been critical factors. PMID:27137438

Structure of coastal community occupational in responsible environmental quality at Tanjung Burung village, Tangerang regency

NASA Astrophysics Data System (ADS)

Syahdanul, Darul; Sumabrata, Jachrizal; Darmajanti, Linda

2018-03-01

Tanjung Burung Village is an area located on the river mouth. The position makes the occupational structure of the community has a relationship with the environmental conditions of the river mouth. The occupational structure of the estuary community tends to be in the primary sector. However, at present, the environmental condition of the Cisadane River estuary has a quality degradation in terms of the intensity of river water pollution, the frequency of flooding, and the intensity of groundwater contamination. This study aims to analyze the relationship between environmental degradation and changes in occupational structure, and analysis on the quality of life of the community. In collecting and processing data, this research uses sequential exploratory strategy. This process refers to the geographical map of Tanjung Burung Village in 1996, 2006, 2016; Population data of 1995, 2000, 2005, 2011, 2016; as well as environmental quality data from 1995 to 2017. The results of this study show that within 20 years the community has strengthened occupational structure in the tertiary sector. Furthermore, the strengthening of occupational structure in the tertiary sector has not been able to improve the quality of life of Tanjung Burung villagers.

Contributions of historical and contemporary geographic and environmental factors to phylogeographic structure in a Tertiary relict species, Emmenopterys henryi (Rubiaceae).

PubMed

Zhang, Yong-Hua; Wang, Ian J; Comes, Hans Peter; Peng, Hua; Qiu, Ying-Xiong

2016-05-03

Examining how historical and contemporary geographic and environmental factors contribute to genetic divergence at different evolutionary scales is a central yet largely unexplored question in ecology and evolution. Here, we examine this key question by investigating how environmental and geographic factors across different epochs have driven genetic divergence at deeper (phylogeographic) and shallower (landscape genetic) evolutionary scales in the Chinese Tertiary relict tree Emmenopterys henryi. We found that geography played a predominant role at all levels - phylogeographic clades are broadly geographically structured, the deepest levels of divergence are associated with major geological or pre-Quaternary climatic events, and isolation by distance (IBD) primarily explained population genetic structure. However, environmental factors are clearly also important - climatic fluctuations since the Last Interglacial (LIG) have likely contributed to phylogeographic structure, and the population genetic structure (in our AFLP dataset) was partly explained by isolation by environment (IBE), which may have resulted from natural selection in environments with divergent climates. Thus, historical and contemporary geography and historical and contemporary environments have all shaped patterns of genetic structure in E. henryi, and, in fact, changes in the landscape through time have also been critical factors.

A hybrid MD-kMC algorithm for folding proteins in explicit solvent.

PubMed

Peter, Emanuel Karl; Shea, Joan-Emma

2014-04-14

We present a novel hybrid MD-kMC algorithm that is capable of efficiently folding proteins in explicit solvent. We apply this algorithm to the folding of a small protein, Trp-Cage. Different kMC move sets that capture different possible rate limiting steps are implemented. The first uses secondary structure formation as a relevant rate event (a combination of dihedral rotations and hydrogen-bonding formation and breakage). The second uses tertiary structure formation events through formation of contacts via translational moves. Both methods fold the protein, but via different mechanisms and with different folding kinetics. The first method leads to folding via a structured helical state, with kinetics fit by a single exponential. The second method leads to folding via a collapsed loop, with kinetics poorly fit by single or double exponentials. In both cases, folding times are faster than experimentally reported values, The secondary and tertiary move sets are integrated in a third MD-kMC implementation, which now leads to folding of the protein via both pathways, with single and double-exponential fits to the rates, and to folding rates in good agreement with experimental values. The competition between secondary and tertiary structure leads to a longer search for the helix-rich intermediate in the case of the first pathway, and to the emergence of a kinetically trapped long-lived molten-globule collapsed state in the case of the second pathway. The algorithm presented not only captures experimentally observed folding intermediates and kinetics, but yields insights into the relative roles of local and global interactions in determining folding mechanisms and rates.

Deep Resistivity Structure of Mid Valley, Nevada Test Site, Nevada

USGS Publications Warehouse

Wallin, Erin L.; Rodriguez, Brian D.; Williams, Jackie M.

2009-01-01

The U.S. Department of Energy (DOE) and the National Nuclear Security Administration (NNSA) at their Nevada Site Office (NSO) are addressing ground-water contamination resulting from historical underground nuclear testing through the Environmental Management (EM) program and, in particular, the Underground Test Area (UGTA) project. From 1951 to 1992, 828 underground nuclear tests were conducted at the Nevada Test Site northwest of Las Vegas (DOE UGTA, 2003). Most of these tests were conducted hundreds of feet above the ground-water table; however, more than 200 of the tests were near, or within, the water table. This underground testing was limited to specific areas of the Nevada Test Site including Pahute Mesa, Rainier Mesa/Shoshone Mountain (RM-SM), Frenchman Flat, and Yucca Flat. One issue of concern is the nature of the somewhat poorly constrained pre-Tertiary geology and its effects on ground-water flow in the area subsequent to a nuclear test. Ground-water modelers would like to know more about the hydrostratigraphy and geologic structure to support a hydrostratigraphic framework model that is under development for the Rainier Mesa/Shoshone Mountain (RM-SM) Corrective Action Unit (CAU) (National Security Technologies, 2007). During 2003, the U.S. Geological Survey (USGS), in cooperation with the DOE and NNSA-NSO collected and processed data at the Nevada Test Site in and near Yucca Flat (YF) to help define the character, thickness, and lateral extent of the pre-Tertiary confining units. We collected 51 magnetotelluric (MT) and audio-magnetotelluric (AMT) stations for that research (Williams and others, 2005a, 2005b, 2005c, 2005d, 2005e, and 2005f). In early 2005 we extended that research with 26 additional MT data stations (Williams and others, 2006) located on and near Rainier Mesa and Shoshone Mountain (RM-SM). The new stations extended the area of the hydrogeologic study previously conducted in Yucca Flat, further refining what is known about the pre-Tertiary confining units. In particular, a major goal was to define the extent of the upper clastic confining unit (UCCU). The UCCU is composed of late Devonian to Mississippian siliciclastic rocks assigned to the Eleana Formation and Chainman Shale (National Security Technologies, 2007). The UCCU underlies the Yucca Flat area and extends southwestward toward Shoshone Mountain, westward toward Buckboard Mesa, and northwestward toward Rainier Mesa. Late in 2005 we collected data at an additional 14 MT stations in Mid Valley, CP Hills, and northern Yucca Flat. That work was done to better determine the extent and thickness of the UCCU near the boundary between the southeastern RM-SM CAU and the southwestern YF CAU, and also in the northern YF CAU. The MT data have been released in a separate U.S. Geological Survey report (Williams and others, 2007). The Nevada Test Site magnetotelluric data interpretation presented in this report includes the results of detailed two-dimensional (2-D) resistivity modeling for each profile and inferences on the three-dimensional (3-D) character of the geology within the region.

The Tjellefonna fault system of Western Norway: Linking late-Caledonian extension, post-Caledonian normal faulting, and Tertiary rock column uplift with the landslide-generated tsunami event of 1756

NASA Astrophysics Data System (ADS)

Redfield, T. F.; Osmundsen, P. T.

2009-09-01

On February 22, 1756, approximately 15.7 million cubic meters of bedrock were catastrophically released as a giant rockslide into the Langfjorden. Subsequently, three ˜ 40 meter high tsunami waves overwhelmed the village of Tjelle and several other local communities. Inherited structures had isolated a compartment in the hanging wall damage zone of the fjord-dwelling Tjellefonna fault. Because the region is seismically active in oblique-normal mode, and in accordance with scant historical sources, we speculate that an earthquake on a nearby fault may have caused the already-weakened Tjelle hillside to fail. From interpretation of structural, geomorphic, and thermo-chronological data we suggest that today's escarpment topography of Møre og Trøndelag is controlled to a first order by post-rift reactivation of faults parallel to the Mesozoic passive margin. In turn, a number of these faults reactivated Late Caledonian or early post-Caledonian fabrics. Normal-sense reactivation of inherited structures along much of coastal Norway suggests that a structural link exists between the processes that destroy today's mountains and those that created them. The Paleozoic Møre-Trøndelag Fault Complex was reactivated as a normal fault during the Mesozoic and, probably, throughout the Cenozoic until the present day. Its NE-SW trending strands crop out between the coast and the base of a c. 1.7 km high NW-facing topographic 'Great Escarpment.' Well-preserved kinematic indicators and multiple generations of fault products are exposed along the Tjellefonna fault, a well-defined structural and topographic lineament parallel to both the Langfjorden and the Great Escarpment. The slope instability that was formerly present at Tjelle, and additional instabilities currently present throughout the region, may be viewed as the direct product of past and ongoing development of tectonic topography in Møre og Trøndelag county. In the Langfjorden region in particular, structural geometry suggests additional unreleased rock compartments may be isolated and under normal fault control. Although post-glacial rebound and topographically-derived horizontal spreading stresses might in part help drive present-day oblique normal seismicity, the normal-fault-controlled escarpments of Norway were at least partly erected in pre-glacial times. Cretaceous to Early Tertiary post-rift subsidence was interrupted by normal faulting at the innermost portion of the passive margin, imposing a strong tectonic empreinte on the developing landscape.

Developmentally and Culturally Appropriate Screening in Primary Care: Development of the Behavioral Health Checklist

PubMed Central

Koshy, Anson J.; Watkins, Marley W.; Cassano, Michael C.; Wahlberg, Andrea C.; Mautone, Jennifer A.; Blum, Nathan J.

2013-01-01

Objective To evaluate the construct validity of the Behavioral Health Checklist (BHCL) for children aged from 4 to 12 years from diverse backgrounds. Method The parents of 4–12-year-old children completed the BHCL in urban and suburban primary care practices affiliated with a tertiary-care children’s hospital. Across practices, 1,702 were eligible and 1,406 (82.6%) provided consent. Children of participating parents were primarily non-Hispanic black/African American and white/Caucasian from low- to middle-income groups. Confirmatory factor analyses examined model fit for the total sample and subsamples defined by demographic characteristics. Results The findings supported the hypothesized 3-factor structure: Internalizing Problems, Externalizing Problems, and Inattention/Hyperactivity. The model demonstrated adequate to good fit across age-groups, gender, races, income groups, and suburban versus urban practices. Conclusion The findings provide strong evidence of the construct validity, developmental appropriateness, and cultural sensitivity of the BHCL when used for screening in primary care. PMID:23978505

Water-Level Data for the Albuquerque Basin and Adjacent Areas, Central New Mexico, Period of Record Through September 30, 2006

USGS Publications Warehouse

Beman, Joseph E.

2007-01-01

The Albuquerque Basin, located in central New Mexico, is about 100 miles long and 25 to 40 miles wide. The basin is defined as the extent of consolidated and unconsolidated deposits of Tertiary and Quaternary age that encompass the structural Rio Grande Rift within the basin. Drinking-water supplies throughout the basin are currently (2007) obtained solely from ground-water resources. An increase of about 20 percent in the population from 1990 to 2000 also resulted in an increased demand for water. From April 1982 through September 1983, a network of wells was established to monitor changes in ground-water levels throughout the basin. This network consisted of 6 wells with analog-to-digital recorders and 27 wells where water levels were measured monthly. Currently (2007), the network consists of 133 wells and piezometers. This report presents water-level data collected by U.S. Geological Survey personnel at 133 sites through 2007.

Femtosecond spectroscopy probes the folding quality of antibody fragments expressed as GFP fusions in the cytoplasm

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

Didier, P.; Weiss, E.; Sibler, A.-P.

2008-02-22

Time-resolved femtosecond spectroscopy can improve the application of green fluorescent proteins (GFPs) as protein-folding reporters. The study of ultrafast excited-state dynamics (ESD) of GFP fused to single chain variable fragment (scFv) antibody fragments, allowed us to define and measure an empirical parameter that only depends on the folding quality (FQ) of the fusion. This method has been applied to the analysis of genetic fusions expressed in the bacterial cytoplasm and allowed us to distinguish folded and thus functional antibody fragments (high FQ) with respect to misfolded antibody fragments. Moreover, these findings were strongly correlated to the behavior of the samemore » scFvs expressed in animal cells. This method is based on the sensitivity of the ESD to the modifications in the tertiary structure of the GFP induced by the aggregation state of the fusion partner. This approach may be applicable to the study of the FQ of polypeptides over-expressed under reducing conditions.« less

Preliminary isostatic residual gravity map of the Newfoundland Mountains 30' by 60' quadrangle and east part of the Wells 30' by 60' quadrangle, Box Elder County, Utah

USGS Publications Warehouse

Langenheim, Victoria; Athens, N.D.; Churchel, B.A.; Willis, H.; Knepprath, N.E.; Rosario, Jose J.; Roza, J.; Kraushaar, S.M.; Hardwick, C.L.

2013-01-01

A new isostatic residual gravity map of the Newfoundland Mountains and east of the Wells 30×60 quadrangles of Utah is based on compilation of preexisting data and new data collected by the Utah and U.S. Geological Surveys. Pronounced gravity lows occur over Grouse Creek Valley and locally beneath the Great Salt Lake Desert, indicating significant thickness of low-density Tertiary sedimentary rocks and deposits. Gravity highs coincide with exposures of dense pre-Cenozoic rocks in the Newfoundland, Silver Island, and Little Pigeon Mountains. Gravity values measured on pre-Tertiary basement to the north in the Bovine and Hogup Mountains are as much as 10mGal lower. Steep, linear gravity gradients may define basin-bounding faults concealed along the margins of the Newfoundland, Silver Island, and Little Pigeon Mountains, Lemay Island and the Pilot Range.

[Visa at a tertiary hospital].

PubMed

Martínez-Jiménez, S; Lluch-Colomer, A; Desongles-Corrales, T; Bernal-González, D; Santos-Rubio, M D; Alfaro-Lara, E R; Galván-Banqueri, M

2013-01-01

To analyze the visa application process and his activity at a tertiary hosipital. Descriptive study of the drug s visa activity during the period April 2011-April 2012. We designed a database and defined categories on the study variables: patients and recipes. For patients admitted to the Visa Unit, issues detected were recorded based on a previously established classification. 6738 patients were included. They involved the visa of 8,465 recipes. The visa was applied to 170 drugs and nutrition products different, being the majority Tacrolimus. During this period, we detected a total of 420 incidents being the most frequent «No clinical document» (46.67%) and the «Formal completion errors» (28.57%). This work has allowed a more detailed analysis of the activity, the types of incidents and the identification of areas for improvement. Copyright © 2013 SEFH. Published by AULA MEDICA. All rights reserved.

A THIRD OF PATIENTS TREATED AT A TERTIARY LEVEL SURGICAL SERVICE COULD BE TREATED AT A SECONDARY LEVEL FACILITY.

PubMed

Van Straten, S K; Stannard, C J; Bulabula, J; Paul, K; Leong, J; Klipin, M

2017-06-01

South Africa has an overburdened public healthcare system. Some admissions to Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) may not require tertiary care. The numbers and details thereof are uncertain. Clinical research is limited by skills and access to data. A retrospective analysis of Electronic Discharge (ED) summaries from the Department of Surgery at CMJAH between 01 April 2015 and 01 April 2016. An SQL-query of the database generated a .csv file of all discharges with the fields database reference number, length of stay and level of care. The details and level of care of each record were verified by MBBCh 5 medical students using a defined level of care template with review of the full discharge summary. The data was reviewed by a senior clinician. There were 3007 discharge summaries, 97 were not classifiable, two were test records and one was a duplicate. These 100 records were excluded. There were no primary level records. Secondary level patients represented 29% (854) of patients discharged and 19% of total bed days. Tertiary and quaternary together represented 71% of the total patients and 81% of bed days. The average length of stay was 4.31 days for secondary, 6.98 days for tertiary and 9.77 days for quaternary level of care allocation. Almost a third (29%) of patients discharged from CMJAH Department of Surgery were deemed suitable for secondary level care. These admissions have a shorter length of stay and comprise 19% of total bed days. Students and electronic databases are useful research resources.

The role of intraoperative parathyroid hormone testing in patients with tertiary hyperparathyroidism after renal transplantation.

PubMed

Haustein, Silke V; Mack, Eberhard; Starling, James R; Chen, Herbert

2005-12-01

Intraoperative parathyroid hormone (PTH) testing has been shown to accurately define adequacy of parathyroid resection in patients with primary hyperparathyroidism (HPT) and alters the operative management in 10% to 15% of cases. However, the benefit of this technique in patients with tertiary HPT after renal transplantation undergoing parathyroidectomy is unclear. Intraoperative PTH was measured in 32 consecutive patients undergoing parathyroidectomy for tertiary HPT after renal transplantation between March 2001 and November 2004 by using the Elecsys assay at baseline and, subsequently, 5, 10, and 15 minutes after curative resection. The outcomes of these patients were evaluated. All patients were cured after surgery. Of the 32 patients, 29 were found to have parathyroid hyperplasia, while 1 had a single adenoma and 2 had double adenomas. The average drop in intraoperative PTH levels after curative resection was 69 +/- 3.5% at 5 min., 77 +/- 2.3% at 10 minutes, and 83 +/- 3.4% at 15 minutes. PTH testing changed the intraoperative management in 5 (16%) patients. One patient with a single adenoma and 2 patients with double adenomas had a >50% drop at 10 minutes. after excision; therefore, the operation was terminated without further resection. Two patients did not have a >50% drop at 10 minutes after 3.5 gland resection. These patients were explored further, and additional supernumerary parathyroid glands were identified and resected. After resection of these additional glands, the PTH fell by >50%, indicating cure. In patients undergoing parathyroidectomy for tertiary HPT after renal transplantation, a decrease in intraoperative PTH levels >50% at 10 minutes after completion of the operation indicated adequate resection. Furthermore, intraoperative PTH testing altered the operative management in 16% of patients. Therefore, similar to its role in patients with primary HPT, intraoperative PTH testing appears to play an equally important role in the management of patients with tertiary HPT undergoing parathyroidectomy.

Cooperative catalysis by tertiary amino-thioureas: mechanism and basis for enantioselectivity of ketone cyanosilylation.

PubMed

Zuend, Stephan J; Jacobsen, Eric N

2007-12-26

The mechanism of the enantioselective cyanosilylation of ketones catalyzed by tertiary amino-thiourea derivatives was investigated using a combination of experimental and theoretical methods. The kinetic analysis is consistent with a cooperative mechanism in which both the thiourea and the tertiary amine of the catalyst are involved productively in the rate-limiting cyanide addition step. Density functional theory calculations were used to distinguish between mechanisms involving thiourea activation of ketone or of cyanide in the enantioselectivity-determining step. The strong correlation obtained between experimental and calculated ee's for a range of substrates and catalysts provides support for the most favorable calculated transition structures involving amine-bound HCN adding to thiourea-bound ketone. The calculations suggest that enantioselectivity arises from direct interactions between the ketone substrate and the amino-acid derived portion of the catalyst. On the basis of this insight, more enantioselective catalysts with broader substrate scope were prepared and evaluated experimentally.

New Mapping in the Sand Springs Range of Western Nevada Clarifies and Constrains Regional Deformation Sequences of the Luning-Fencemaker Thrust Belt

NASA Astrophysics Data System (ADS)

Czarnecki, S.; Jarvis, J.; Satterfield, J. I.

2016-12-01

The Sand Springs Range in western Nevada exposes Mesozoic through Cenozoic structures of the eastern Sierra Nevada, Luning-Fencemaker Thrust Belt (LFTB), Basin and Range province, and Walker Lane. A recent undergraduate geologic mapping project in the northern Sand Springs Range (nSSR) set out to map igneous intrusions in detail, specifically smaller intrusions which had not been a focus in previous work. This was accomplished using different techniques including mapping at a smaller scale (1:8000 vs. 1:24000), locating contacts and faults using handheld GPS, and focusing on relationships between metamorphic tectonites and igneous units. This revealed key cross-cutting relations between structures and diverse Triassic through Tertiary igneous rocks as well as distinctions between the nSSR and the surrounding LFTB assemblages. During our mapping we identified four metamorphic tectonite map units, Cretaceous granitoid and diorite plutons and sills, Tertiary rhyolite sills and dikes, and interbedded Tertiary basalt and ash flow tuff. The cross-cutting relations of these units overturn previously published sequences of events and constrain the timing of a deformation sequence which differs from the surrounding LFTB assemblages. We found that the nSSR contains three phases of deformation: a pre-LFTB syn-metamorphic event which achieved amphibolite facies that is not described elsewhere in the LFTB (D1), followed by two non-metamorphic folding and thrusting phases characteristic of the LFTB (D2 and D3). Our mapping provided four key timing constraints. First, D1 axial-planar cleavage (S1) deformed Triassic intrusions. Second, Cretaceous granitoid and diorite units cross-cut S1 foliation, D1 folds, and low-angle faults. Third, Cretaceous and Tertiary sills that locally terminate at a low-angle fault actually post-dated faulting. Fourth, cross-cutting relations showed a basaltic lava previously mapped as Jurassic is actually Tertiary. The large Sand Springs Pluton was the only intrusion mapped in detail during previous studies; but our mapping has demonstrated the importance of both small and large intrusions in understanding the overall structural history of a complex area. This project was supported by research grants from Angelo State University and the Southwest Section AAPG.

Expanding the Concepts in Protein Structure-Function Relationships and Enzyme Kinetics: Teaching Using Morpheeins

ERIC Educational Resources Information Center

Lawrence, Sarah H.; Jaffe, Eileen K.

2008-01-01

A morpheein is a homo-oligomeric protein that can exist as an ensemble of physiologically significant and functionally distinct alternate quaternary assemblies. Morpheeins exist in nature and use conformational equilibria between different tertiary structures to form distinct oligomers as a means of regulating their function. Notably, alternate…

Basics of Sterile Compounding: Manipulating Peptides and Proteins.

PubMed

Akers, Michael J

2017-01-01

Biopharmaceuticals contain primary and secondary structure, which offer few problems. It is the tertiary structure that causes problems, resulting in both physical and chemical stability issues. The thrust of this article is to share briefly what can be done to minimize these problems. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Principles of protein folding--a perspective from simple exact models.

PubMed Central

Dill, K. A.; Bromberg, S.; Yue, K.; Fiebig, K. M.; Yee, D. P.; Thomas, P. D.; Chan, H. S.

1995-01-01

General principles of protein structure, stability, and folding kinetics have recently been explored in computer simulations of simple exact lattice models. These models represent protein chains at a rudimentary level, but they involve few parameters, approximations, or implicit biases, and they allow complete explorations of conformational and sequence spaces. Such simulations have resulted in testable predictions that are sometimes unanticipated: The folding code is mainly binary and delocalized throughout the amino acid sequence. The secondary and tertiary structures of a protein are specified mainly by the sequence of polar and nonpolar monomers. More specific interactions may refine the structure, rather than dominate the folding code. Simple exact models can account for the properties that characterize protein folding: two-state cooperativity, secondary and tertiary structures, and multistage folding kinetics--fast hydrophobic collapse followed by slower annealing. These studies suggest the possibility of creating "foldable" chain molecules other than proteins. The encoding of a unique compact chain conformation may not require amino acids; it may require only the ability to synthesize specific monomer sequences in which at least one monomer type is solvent-averse. PMID:7613459

Thermal aggregation of glycated bovine serum albumin.

PubMed

Rondeau, Philippe; Navarra, Giovanna; Cacciabaudo, Francesco; Leone, Maurizio; Bourdon, Emmanuel; Militello, Valeria

2010-04-01

Aggregation and glycation processes in proteins have a particular interest in medicine fields and in food technology. Serum albumins are model proteins which are able to self-assembly in aggregates and also sensitive to a non-enzymatic glycation in cases of diabetes. In this work, we firstly reported a study on the glycation and oxidation effects on the structure of bovine serum albumin (BSA). The experimental approach is based on the study of conformational changes of BSA at secondary and tertiary structures by FTIR absorption and fluorescence spectroscopy, respectively. Secondly, we analysed the thermal aggregation process on BSA glycated with different glucose concentrations. Additional information on the aggregation kinetics are obtained by light scattering measurements. The results show that glycation process affects the native structure of BSA. Then, the partial unfolding of the tertiary structure which accompanies the aggregation process is similar both in native and glycated BSA. In particular, the formation of aggregates is progressively inhibited with growing concentration of glucose incubated with BSA. These results bring new insights on how aggregation process is affected by modification of BSA induced by glycation. Copyright 2009 Elsevier B.V. All rights reserved.

Epitope targeting of tertiary protein structure enables target-guided synthesis of a potent in-cell inhibitor of botulinum neurotoxin.

PubMed

Farrow, Blake; Wong, Michelle; Malette, Jacquie; Lai, Bert; Deyle, Kaycie M; Das, Samir; Nag, Arundhati; Agnew, Heather D; Heath, James R

2015-06-08

Botulinum neurotoxin (BoNT) serotype A is the most lethal known toxin and has an occluded structure, which prevents direct inhibition of its active site before it enters the cytosol. Target-guided synthesis by in situ click chemistry is combined with synthetic epitope targeting to exploit the tertiary structure of the BoNT protein as a landscape for assembling a competitive inhibitor. A substrate-mimicking peptide macrocycle is used as a direct inhibitor of BoNT. An epitope-targeting in situ click screen is utilized to identify a second peptide macrocycle ligand that binds to an epitope that, in the folded BoNT structure, is active-site-adjacent. A second in situ click screen identifies a molecular bridge between the two macrocycles. The resulting divalent inhibitor exhibits an in vitro inhibition constant of 165 pM against the BoNT/A catalytic chain. The inhibitor is carried into cells by the intact holotoxin, and demonstrates protection and rescue of BoNT intoxication in a human neuron model. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Molecular crowding overcomes the destabilizing effects of mutations in a bacterial ribozyme

DOE PAGES

Lee, Hui-Ting; Kilburn, D.; Behrouzi, R.; ...

2014-12-05

The native structure of the Azoarcus group I ribozyme is stabilized by the cooperative formation of tertiary interactions between double helical domains. Thus, even single mutations that break this network of tertiary interactions reduce ribozyme activity in physiological Mg2+ concentrations. Here, we report that molecular crowding comparable to that in the cell compensates for destabilizing mutations in the Azoarcus ribozyme. Small angle X-ray scattering, native polyacrylamide gel electrophoresis and activity assays were used to compare folding free energies in dilute and crowded solutions containing 18% PEG1000. Crowder molecules allowed the wild-type and mutant ribozymes to fold at similarly low Mg2+more » concentrations and stabilized the active structure of the mutant ribozymes under physiological conditions. This compensation helps explains why ribozyme mutations are often less deleterious in the cell than in the test tube. Nevertheless, crowding did not rescue the high fraction of folded but less active structures formed by double and triple mutants. We conclude that crowding broadens the fitness landscape by stabilizing compact RNA structures without improving the specificity of self-assembly.« less

Molecular crowding overcomes the destabilizing effects of mutations in a bacterial ribozyme

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

Lee, Hui-Ting; Kilburn, D.; Behrouzi, R.

The native structure of the Azoarcus group I ribozyme is stabilized by the cooperative formation of tertiary interactions between double helical domains. Thus, even single mutations that break this network of tertiary interactions reduce ribozyme activity in physiological Mg2+ concentrations. Here, we report that molecular crowding comparable to that in the cell compensates for destabilizing mutations in the Azoarcus ribozyme. Small angle X-ray scattering, native polyacrylamide gel electrophoresis and activity assays were used to compare folding free energies in dilute and crowded solutions containing 18% PEG1000. Crowder molecules allowed the wild-type and mutant ribozymes to fold at similarly low Mg2+more » concentrations and stabilized the active structure of the mutant ribozymes under physiological conditions. This compensation helps explains why ribozyme mutations are often less deleterious in the cell than in the test tube. Nevertheless, crowding did not rescue the high fraction of folded but less active structures formed by double and triple mutants. We conclude that crowding broadens the fitness landscape by stabilizing compact RNA structures without improving the specificity of self-assembly.« less

Is the Conformational Ensemble of Alzheimer’s Aβ10-40 Peptide Force Field Dependent?

PubMed Central

Siwy, Christopher M.

2017-01-01

By applying REMD simulations we have performed comparative analysis of the conformational ensembles of amino-truncated Aβ10-40 peptide produced with five force fields, which combine four protein parameterizations (CHARMM36, CHARMM22*, CHARMM22/cmap, and OPLS-AA) and two water models (standard and modified TIP3P). Aβ10-40 conformations were analyzed by computing secondary structure, backbone fluctuations, tertiary interactions, and radius of gyration. We have also calculated Aβ10-40 3JHNHα-coupling and RDC constants and compared them with their experimental counterparts obtained for the full-length Aβ1-40 peptide. Our study led us to several conclusions. First, all force fields predict that Aβ adopts unfolded structure dominated by turn and random coil conformations. Second, specific TIP3P water model does not dramatically affect secondary or tertiary Aβ10-40 structure, albeit standard TIP3P model favors slightly more compact states. Third, although the secondary structures observed in CHARMM36 and CHARMM22/cmap simulations are qualitatively similar, their tertiary interactions show little consistency. Fourth, two force fields, OPLS-AA and CHARMM22* have unique features setting them apart from CHARMM36 or CHARMM22/cmap. OPLS-AA reveals moderate β-structure propensity coupled with extensive, but weak long-range tertiary interactions leading to Aβ collapsed conformations. CHARMM22* exhibits moderate helix propensity and generates multiple exceptionally stable long- and short-range interactions. Our investigation suggests that among all force fields CHARMM22* differs the most from CHARMM36. Fifth, the analysis of 3JHNHα-coupling and RDC constants based on CHARMM36 force field with standard TIP3P model led us to an unexpected finding that in silico Aβ10-40 and experimental Aβ1-40 constants are generally in better agreement than these quantities computed and measured for identical peptides, such as Aβ1-40 or Aβ1-42. This observation suggests that the differences in the conformational ensembles of Aβ10-40 and Aβ1-40 are small and the former can be used as proxy of the full-length peptide. Based on this argument, we concluded that CHARMM36 force field with standard TIP3P model produces the most accurate representation of Aβ10-40 conformational ensemble. PMID:28085875

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

Miles, Andrew J.; Fedosova, Natalya U.; Hoffmann, Søren V.

Highlights: •Ouabain binding to pig and shark Na,K-ATPase enhances thermal stability. •Ouabain stabilises both membrane-bound and solubilised Na,K-ATPase. •Synchrotron radiation circular dichroism is used for structure determination. •Secondary structure in general is not affected by ouabain binding. •Stabilisation is due to re-arrangement of tertiary structure. -- Abstract: Cardiotonic steroids such as ouabain bind with high affinity to the membrane-bound cation-transporting P-type Na,K-ATPase, leading to complete inhibition of the enzyme. Using synchrotron radiation circular dichroism spectroscopy we show that the enzyme-ouabain complex is less susceptible to thermal denaturation (unfolding) than the ouabain-free enzyme, and this protection is observed with Na,K-ATPase purifiedmore » from pig kidney as well as from shark rectal glands. It is also shown that detergent-solubilised preparations of Na,K-ATPase are stabilised by ouabain, which could account for the successful crystallisation of Na,K-ATPase in the ouabain-bound form. The secondary structure is not significantly affected by the binding of ouabain. Ouabain appears however, to induce a reorganization of the tertiary structure towards a more compact protein structure which is less prone to unfolding; recent crystal structures of the two enzymes are consistent with this interpretation. These circular dichroism spectroscopic studies in solution therefore provide complementary information to that provided by crystallography.« less

[Governance of tertiary referral hospitals in the Democratic Republic of the Congo: a critical interpretive synthesis of the literature].

PubMed

Karemere, H; Kahindo, J B; Ribesse, N; Macq, J

2013-01-01

Because hospitals are complex enterprises requiring adaptive systems, it is appropriate to apply the theory and terminology of governance or even better adaptive governance to the interpretation of their management. This study focused on understanding hospital governance in Logo, Bunia, and Katana, three hospitals in two regions of the eastern DRC, which has been characterized by intermittent armed conflict since 1996. In such a context of war and continuous insecurity, how can governance be interpreted for hospitals required to adapt to a constantly changing environment to be able to continue to provide health care? A critical interpretive synthesis of the literature, identified by searching for keywords related to governance. The concepts of governance, adaptive governance, performance, leadership, and complex adaptive system concepts are defined. The interpretation of the concepts helps us to better understand (1) the hospital as a complex adaptive system, (2) the governance of tertiary referral hospitals, (3) analysis of hospital performance, and (4) leadership for good governance of these hospitals. The interpretation of these concepts raises several questions about their application to the eastern DRC. Conclusion. This critical interpretive synthesis opens the door to a new way of exploring tertiary hospitals and their governance in the eastern DRC.

Contemporary Parenteral Antiplatelet Bridging Strategies: A Single-Center Real-World Experience at a Tertiary Care Center.

PubMed

Stern, Gretchen; Rimsans, Jessica; Qamar, Arman; Vaduganathan, Muthiah; Bhatt, Deepak L

2018-03-13

Oral antiplatelet therapy may require interruption soon after percutaneous coronary intervention (PCI) or acute coronary syndrome. The optimal parenteral antiplatelet bridge strategy with glycoprotein IIb/IIIa inhibitors or cangrelor, a P2Y12 inhibitor, is unclear. We explore real-world use of cangrelor or eptifibatide for antiplatelet bridging at a large tertiary-care center. Thirty-one patients (9 eptifibatide, 20 cangrelor, and 2 both) received bridge therapy from October 2015 to June 2017. Primary bridge therapy indications included surgery (68%), limited enteral access/absorption (16%), and high-perceived bleed risk (16%). Median duration of bridge therapy was 61 (20-100) hours for cangrelor and 83 (19-98) hours for eptifibatide. Severe/life-threatening bleeding or stent thrombosis was not observed. GUSTO-defined bleeding occurred in 30% (cangrelor) and 27% (eptifibatide). Initial dosing errors occurred in 23% of patients. Death during hospitalization occurred in 16% of patients. Parenteral antiplatelet bridging was used for ~3 days in this single-center, tertiary care experience, commonly for unplanned surgery following PCI. Despite high-risk presentations with >15% in-hospital mortality, efficacy profiles were reassuring with no identified stent thrombosis, but bleeding and dosing errors were common. Antiplatelet bridging should only be used in well-selected patients at the appropriate dose for the minimal necessary duration.

Geologic and geomorphic controls of coal development in some Tertiary Rocky Mountain basins, USA

USGS Publications Warehouse

Flores, R.M.

1993-01-01

Previous investigations have not well defined the controls on the development of minable coals in fluvial environments. This study was undertaken to provide a clearer understanding of these controls, particularly in of the lower Tertiary coal-bearing deposits of the Raton and Powder River basins in the Rocky Mountain region of the United States. In this region, large amounts of coals accumulated in swamps formed in the flow-through fluvial systems that infilled these intermontane basins. Extrabasinal and intrabasinal tectonism partly controlled the stratigraphic and facies distributions of minable coal deposits. The regional accumulation of coals was favored by the rapid basin subsidence coupled with minimal uplift of the source area. During these events, coals developed in swamps associated with anastomosed and meandering fluvial systems and alluvial fans. The extensive and high rate of sediment input from these fluvial systems promoted the formation of ombrotrophic, raised swamps, which produced low ash and anomalously thick coals. The petrology and palynology of these coals, and the paleobotany of the associated sediments, suggest that ombrotrophic, raised swamps were common in the Powder River Basin, where the climate during the early Tertiary was paratropical. The paleoecology of these swamps is identical to that of the modern ombrotrophic, raised swamps of the Baram and Mahakam Rivers of Borneo. ?? 1993.

An Amino Acid Packing Code for α-helical Structure and Protein Design

PubMed Central

Joo, Hyun; Chavan, Archana G.; Phan, Jamie; Day, Ryan; Tsai, Jerry

2012-01-01

This work demonstrates that all packing in α-helices can be simplified to repetitive patterns of a single motif: the knob-socket. Using the precision of Voronoi Polyhedra/Deluaney Tessellations to identify contacts, the knob-socket is a 4 residue tetrahedral motif: a knob residue on one α-helix packs into the 3 residue socket on another α-helix. The principle of the knob-socket model relates the packing between levels of protein structure: the intra-helical packing arrangements within secondary structure that permit inter-helix tertiary packing interactions. Within an α-helix, the 3 residue sockets arrange residues into a uniform packing lattice. Inter-helix packing results from a definable pattern of interdigitated knob-socket motifs between 2 α-helices. Furthermore, the knob-socket model classifies 3 types of sockets: 1) free: favoring only intra-helical packing, 2) filled: favoring inter-helical interactions and 3) non: disfavoring α-helical structure. The amino acid propensities in these 3 socket classes essentially represent an amino acid code for structure in α-helical packing. Using this code, a novel yet straightforward approach for the design of α-helical structure was used to validate the knob-socket model. Unique sequences for 3 peptides were created to produce a predicted amount of α-helical structure: mostly helical, some helical, and no-helix. These 3 peptides were synthesized and helical content assessed using CD spectroscopy. The measured α-helicity of each peptide was consistent with the expected predictions. These results and analysis demonstrate that the knob-socket motif functions as the basic unit of packing and presents an intuitive tool to decipher the rules governing packing in protein structure. PMID:22426125

Arc is a flexible modular protein capable of reversible self-oligomerization

PubMed Central

Myrum, Craig; Baumann, Anne; Bustad, Helene J.; Flydal, Marte Innselset; Mariaule, Vincent; Alvira, Sara; Cuéllar, Jorge; Haavik, Jan; Soulé, Jonathan; Valpuesta, José Maria; Márquez, José Antonio; Martinez, Aurora; Bramham, Clive R.

2015-01-01

The immediate early gene product Arc (activity-regulated cytoskeleton-associated protein) is posited as a master regulator of long-term synaptic plasticity and memory. However, the physicochemical and structural properties of Arc have not been elucidated. In the present study, we expressed and purified recombinant human Arc (hArc) and performed the first biochemical and biophysical analysis of hArc's structure and stability. Limited proteolysis assays and MS analysis indicate that hArc has two major domains on either side of a central more disordered linker region, consistent with in silico structure predictions. hArc's secondary structure was estimated using CD, and stability was analysed by CD-monitored thermal denaturation and differential scanning fluorimetry (DSF). Oligomerization states under different conditions were studied by dynamic light scattering (DLS) and visualized by AFM and EM. Biophysical analyses show that hArc is a modular protein with defined secondary structure and loose tertiary structure. hArc appears to be pyramid-shaped as a monomer and is capable of reversible self-association, forming large soluble oligomers. The N-terminal domain of hArc is highly basic, which may promote interaction with cytoskeletal structures or other polyanionic surfaces, whereas the C-terminal domain is acidic and stabilized by ionic conditions that promote oligomerization. Upon binding of presenilin-1 (PS1) peptide, hArc undergoes a large structural change. A non-synonymous genetic variant of hArc (V231G) showed properties similar to the wild-type (WT) protein. We conclude that hArc is a flexible multi-domain protein that exists in monomeric and oligomeric forms, compatible with a diverse, hub-like role in plasticity-related processes. PMID:25748042

The Colorado front range: anatomy of a Laramide uplift

USGS Publications Warehouse

Kellogg, Karl; Bryant, Bruce; Reed, John C.

2004-01-01

Along a transect across the Front Range from Denver to the Blue River valley near Dillon, the trip explores the geologic framework and Laramide (Late Cretaceous to early Eocene) uplift history of this basement-cored mountain range. Specific items for discussion at various stops are (1) the sedimentary and structural record along the upturned eastern margin of the range, which contains several discontinuous, east-directed reverse faults; (2) the western structural margin of the range, which contains a minimum of 9 km of thrust overhang and is significantly different in structural style from the eastern margin; (3) mid- to late-Tertiary modifications to the western margin of the range from extensional faulting along the northern Rio Grande rift trend; (4) the thermal and uplift history of the range as revealed by apatite fission track analysis; (5) the Proterozoic basement of the range, including the significance of northeast-trending shear zones; and (6) the geologic setting of the Colorado mineral belt, formed during Laramide and mid-Tertiary igneous activity.

Molecular identification of aiiA homologous gene from endophytic Enterobacter species and in silico analysis of putative tertiary structure of AHL-lactonase.

PubMed

Rajesh, P S; Rai, V Ravishankar

2014-01-03

The aiiA homologous gene known to encode AHL- lactonase enzyme which hydrolyze the N-acylhomoserine lactone (AHL) quorum sensing signaling molecules produced by Gram negative bacteria. In this study, the degradation of AHL molecules was determined by cell-free lysate of endophytic Enterobacter species. The percentage of quorum quenching was confirmed and quantified by HPLC method (p<0.0001). Amplification and sequence BLAST analysis showed the presence of aiiA homologous gene in endophytic Enterobacter asburiae VT65, Enterobacter aerogenes VT66 and Enterobacter ludwigii VT70 strains. Sequence alignment analysis revealed the presence of two zinc binding sites, "HXHXDH" motif as well as tyrosine residue at the position 194. Based on known template available at Swiss-Model, putative tertiary structure of AHL-lactonase was constructed. The result showed that novel endophytic strains of Enterobacter genera encode the novel aiiA homologous gene and its structural importance for future study. Copyright © 2013 Elsevier Inc. All rights reserved.

An excited state underlies gene regulation of a transcriptional riboswitch

PubMed Central

Zhao, Bo; Guffy, Sharon L.; Williams, Benfeard; Zhang, Qi

2017-01-01

Riboswitches control gene expression through ligand-dependent structural rearrangements of the sensing aptamer domain. However, we found that the Bacillus cereus fluoride riboswitch aptamer adopts identical tertiary structures in solution with and without ligand. Using chemical exchange saturation transfer (CEST) NMR spectroscopy, we revealed that the structured ligand-free aptamer transiently accesses a low-populated (~1%) and short-lived (~3 ms) excited conformational state that unravels a conserved ‘linchpin’ base pair to signal transcription termination. Upon fluoride binding, this highly localized fleeting process is allosterically suppressed to activate transcription. We demonstrated that this mechanism confers effective fluoride-dependent gene activation over a wide range of transcription rates, which is essential for robust toxicity response across diverse cellular conditions. These results unveil a novel switching mechanism that employs ligand-dependent suppression of an aptamer excited state to coordinate regulatory conformational transitions rather than adopting distinct aptamer ground-state tertiary architectures, exemplifying a new mode of ligand-dependent RNA regulation. PMID:28719589

Effects of local geology on ground motion in the San Francisco Bay region, California—A continued study

USGS Publications Warehouse

Gibbs, James F.; Borcherdt, Roger D.

1974-01-01

Measurements of ground motion generated by nuclear explosions in Nevada have been completed for 99 locations in the San Francisco Bay region, California. The seismograms, Fourier amplitude spectra, spectral amplification curves for the signal, and the Fourier amplitude spectra of the seismic noise are presented for 60 locations. Analog amplifications, based on the maximum signal amplitude, are computed for an additional 39 locations. The recordings of the nuclear explosions show marked amplitude variations which are consistently related to the local geologic conditions of the recording site. The average spectral amplifications observed for vertical and horizontal ground motions are, respectively: (1, 1) for granite, (1.5, 1.6) for the Franciscan Formation, (2.3, 2.3), for other pre-Tertiary and Tertiary rocks, (3.0, 2.7) for the Santa Clara Formation, (3.3, 4.4) for older bay sediments, and (3.7, 11.3) for younger bay mud. Spectral amplification curves define predominant ground frequencies for younger bay mud sites and for some older bay sediment sites. The predominant frequencies for most sites were not clearly defined by the amplitude spectra computed from the seismic background noise. The intensities ascribed to various sites in the San Francisco Bay region for the California earthquake of April 18, 1906, are strongly dependent on distance from the zone of surface faulting and the geological character of the ground. Considering only those sites (approximately one square city block in size) for which there is good evidence for the degree of ascribed intensity, the intensities for 917 sites on Franciscan rocks generally decrease with the logarithm of distance as Intensity = 2.69 - 1.90 log (Distance Km). For sites on other geologic units, intensity increments, derived from this empirical rela.tion, correlate strongly with the Average Horizontal Spectral Amplifications (MISA) according to the empirical relation Intensity Increment= 0.27 + 2.70 log(AHSA). Average intensity increments predicted for various geologic units are -0.3 for granite, 0.2 for Franciscan Formation, 0.6 for other pre-Tertiary, Tertiary bedrock, 0.8 for Santa Clara Formation, 1 .3 for older bay sediments, 2.4 for younger bay mud. These empirical relations, together with detailed geologic maps, delineate areas in the San Francisco Bay region of potentially high intensity from future earthquakes on either the San Andreas fault or the Hayward fault.

Structural geologic analysis of Nevada using ERTS-1 images: A preliminary report

NASA Technical Reports Server (NTRS)

Rowan, L. C.; Wetlaufer, P. H.

1973-01-01

Structural analysis of Nevada using ERTS-1 images showns several previously unrecognized lineaments which may be the surface manifestations of major fault or fracture zones. Principle trends are NE, NW, NNE-NNW, and ENE. Two lineament zones, the Walker Lane and Midas Trench lineament system, transect the predominantly NNE-NNW trending mountain ranges for more than 500 km. 50 circular features have been delineated. Comparison with known Tertiary volcanic centers and reference to geologic maps suggest 8 new centers. Preferred distribution of mines and Tertiary volcanic centers along some of the major lineament suggests a genetic relationship. The intersection of three previously unmapped lineaments in northwestern Nevada is the location of a highly productive metallogenic district. In the Walker Lane, ENE-trending lineament appear to be related to the occurrence of productive ore deposits.

Adolescent smoking and tertiary education: opposing pathways linking socio-economic background to alcohol consumption.

PubMed

Green, Michael J; Leyland, Alastair H; Sweeting, Helen; Benzeval, Michaela

2016-08-01

If socio-economic disadvantage is associated with more adolescent smoking, but less participation in tertiary education, and smoking and tertiary education are both associated with heavier drinking, these may represent opposing pathways to heavy drinking. This paper examines contextual variation in the magnitude and direction of these associations. Comparing cohort studies. United Kingdom. Participants were from the 1958 National Child Development Study (NCDS58; n = 15 672), the British birth cohort study (BCS70; n = 12 735) and the West of Scotland Twenty-07 1970s cohort (T07; n = 1515). Participants self-reported daily smoking and weekly drinking in adolescence (age 16 years) and heavy drinking (> 14/21 units in past week) in early adulthood (ages 22-26 years). Parental occupational class (manual versus non-manual) indicated socio-economic background. Education beyond age 18 was coded as tertiary. Models were adjusted for parental smoking and drinking, family structure and adolescent psychiatric distress. Respondents from a manual class were more likely to smoke and less likely to enter tertiary education (e.g. in NCDS58, probit coefficients were 0.201 and -0.765, respectively; P < 0.001 for both) than respondents from a non-manual class. Adolescent smokers were more likely to drink weekly in adolescence (0.346; P < 0.001) and more likely to drink heavily in early adulthood (0.178; P < 0.001) than adolescent non-smokers. Respondents who participated in tertiary education were more likely to drink heavily in early adulthood (0.110 for males, 0.182 for females; P < 0.001 for both) than respondents with no tertiary education. With some variation in magnitude, these associations were consistent across all three cohorts. In Britain, young adults are more likely to drink heavily both if they smoke and participate in tertiary education (college and university) despite socio-economic background being associated in opposite directions with these risk factors. © 2016 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

Blast-Induced Acceleration in a Shock Tube: Distinguishing Primary and Tertiary Blast Injury

DTIC Science & Technology

2016-10-01

objects of varied areal densities to define relations of blast flow conditions to acceleration and displacement , we have begun examination of the effects... displacement from other biomechanical components and effects of the shockwave. 15. SUBJECT TERMS Key words or phrases identifying major concepts in the...and total pressure, positive phase duration, and impulse) and acceleration and displacement of a wide range of inanimate objects, we have continued

Origin and late quaternary tectonism of a western Canadian continental shelf trough

NASA Astrophysics Data System (ADS)

Moslow, Thomas F.; Luternauer, John L.; Rohr, Kristin

1991-08-01

Analyses of high resolution and multi-channel seismic profiles from the central continental shelf of western Canada ascribe a late Quaternary glacial origin to large-scale troughs. Along the margins of Moresby Trough, one of three large-scale cross-shelf bathymetric depressions in Queen Charlotte Sound, seismic profiles within Quaternary sediments show a divergence of reflectors, thickening and folding of seismic units, and concavity of reflectors suggestive of drag. Compactional subsidence, growth faulting, and compaction faulting are also observed. Fault traces commonly terminate below the seabed. Deformation of Quaternary sediments due to faulting is plastic in nature and maximum offset of reflectors is 2.5 m. The observed Quaternary deformation appears to be a product of rapid deposition, loading and subsidence of late Quaternary sediment, which is unrelated to seismic activity. In addition, Quaternary faulting was probably activated by post-glacial loading and isostatic rebound of consolidated Tertiary strata along the margins of continental shelf troughs. The presence of mass movement (slump or debris flow) deposits overlying lithified Tertiary strata along the flanks of Moresby Trough provides the only evidence of seismic activity in the study area. The lack of a mud drape over these deposits implies a late Holocene age for the timing of their emplacement. The Quaternary troughs are incised into Tertiary-aged sedimentary fill of the Queen Charlotte basin. Previous workers had interpreted seafloor escarpments paralleling the trough margins to indicate that the location of Moresby Trough was controlled by renewed or continued activity on Tertiary-aged faults. A multi-channel seismic line across Moresby Trough shows that such an escarpment on the seafloor does not correlate to faults either in the Tertiary basin fill or the underlying basement. Tertiary reflectors are continuous underneath Moresby Trough; the seafloor escarpment is an erosional feature and was not created by reactivation of Tertiary structures. Trough erosion and subsequent fill (up to 175 m thick) are entirely of Quaternary age.

Managing patient pathways to achieve lung cancer waiting time targets: mixed methods study

PubMed Central

Ip, Hugh; Amer, Tarik; Dangoor, Michael; Zamir, Affan; Gibbings-Isaac, Darryl; Kochhar, Ranjeev; Heymann, Timothy

2012-01-01

Objectives England's National Health Service (NHS) introduced a 62-day target, from referral to treatment, to make lung cancer patient pathways more efficient. This study aims to understand pathway delays that lead to breaches of the target when patients need care in both secondary and tertiary setting, so more than one institution is involved. Design Mixed methods cross case analysis. Setting Two tertiary referral hospitals in London. Participants Database records of 53 patients were analysed. Nineteen sets of patient notes were used for pathway mapping. Seventeen doctors, four nurses, eight managers and administrators were interviewed. Main outcome measures Qualitative methods include pathway mapping and semi-structured interviews. Quantitative analysis of patient pathway times from cancer services records. Results The majority of the patient pathway (68.4%) is spent in secondary centres. There is more variability in the processes of secondary centres but tertiary centres do not have perfect processes either. Three themes emerged from discussions: information flows, pathway performance and the role of the multidisciplinary approach. Conclusions The actions of secondary centres have a greater influence on whether a patient breaches the 62-day target, compared with tertiary centres. Nevertheless variability exists in both, with potential for improvement. PMID:23162682

The complex folding pathways of protein A suggest a multiple-funnelled energy landscape

NASA Astrophysics Data System (ADS)

St-Pierre, Jean-Francois; Mousseau, Normand; Derreumaux, Philippe

2008-01-01

Folding proteins into their native states requires the formation of both secondary and tertiary structures. Many questions remain, however, as to whether these form into a precise order, and various pictures have been proposed that place the emphasis on the first or the second level of structure in describing folding. One of the favorite test models for studying this question is the B domain of protein A, which has been characterized by numerous experiments and simulations. Using the activation-relaxation technique coupled with a generic energy model (optimized potential for efficient peptide structure prediction), we generate more than 50 folding trajectories for this 60-residue protein. While the folding pathways to the native state are fully consistent with the funnel-like description of the free energy landscape, we find a wide range of mechanisms in which secondary and tertiary structures form in various orders. Our nonbiased simulations also reveal the presence of a significant number of non-native β and α conformations both on and off pathway, including the visit, for a non-negligible fraction of trajectories, of fully ordered structures resembling the native state of nonhomologous proteins.

Sequential events in the irreversible thermal denaturation of human brain-type creatine kinase by spectroscopic methods.

PubMed

Gao, Yan-Song; Su, Jing-Tan; Yan, Yong-Bin

2010-06-25

The non-cooperative or sequential events which occur during protein thermal denaturation are closely correlated with protein folding, stability, and physiological functions. In this research, the sequential events of human brain-type creatine kinase (hBBCK) thermal denaturation were studied by differential scanning calorimetry (DSC), CD, and intrinsic fluorescence spectroscopy. DSC experiments revealed that the thermal denaturation of hBBCK was calorimetrically irreversible. The existence of several endothermic peaks suggested that the denaturation involved stepwise conformational changes, which were further verified by the discrepancy in the transition curves obtained from various spectroscopic probes. During heating, the disruption of the active site structure occurred prior to the secondary and tertiary structural changes. The thermal unfolding and aggregation of hBBCK was found to occur through sequential events. This is quite different from that of muscle-type CK (MMCK). The results herein suggest that BBCK and MMCK undergo quite dissimilar thermal unfolding pathways, although they are highly conserved in the primary and tertiary structures. A minor difference in structure might endow the isoenzymes dissimilar local stabilities in structure, which further contribute to isoenzyme-specific thermal stabilities.

A first line of stress defense: small heat shock proteins and their function in protein homeostasis.

PubMed

Haslbeck, Martin; Vierling, Elizabeth

2015-04-10

Small heat shock proteins (sHsps) are virtually ubiquitous molecular chaperones that can prevent the irreversible aggregation of denaturing proteins. sHsps complex with a variety of non-native proteins in an ATP-independent manner and, in the context of the stress response, form a first line of defense against protein aggregation in order to maintain protein homeostasis. In vertebrates, they act to maintain the clarity of the eye lens, and in humans, sHsp mutations are linked to myopathies and neuropathies. Although found in all domains of life, sHsps are quite diverse and have evolved independently in metazoans, plants and fungi. sHsp monomers range in size from approximately 12 to 42kDa and are defined by a conserved β-sandwich α-crystallin domain, flanked by variable N- and C-terminal sequences. Most sHsps form large oligomeric ensembles with a broad distribution of different, sphere- or barrel-like oligomers, with the size and structure of the oligomers dictated by features of the N- and C-termini. The activity of sHsps is regulated by mechanisms that change the equilibrium distribution in tertiary features and/or quaternary structure of the sHsp ensembles. Cooperation and/or co-assembly between different sHsps in the same cellular compartment add an underexplored level of complexity to sHsp structure and function. Copyright © 2015 Elsevier Ltd. All rights reserved.

Use of optical coherence tomography in delineating airways microstructure: comparison of OCT images to histopathological sections

NASA Astrophysics Data System (ADS)

Yang, Ying; Whiteman, Suzanne; Gey van Pittius, Daniel; He, Yonghong; Wang, Ruikang K.; Spiteri, Monica A.

2004-04-01

An ideal diagnostic system for the human airways should be able to detect and define early development of premalignant pathological lesions, to facilitate optimal curative treatment and prevent irreversible and/or invasive lung disease. There is great need for exploration of safe, repeatable imaging techniques which can run at real-time and with high spatial resolution. In this study, optical coherence tomography (OCT) was utilized to acquire cross-sectional images of upper and lower airways using fresh pig lung resections as a model system. Obtained OCT images were compared with parallel tissue characterization by conventional histological analysis. Our objective was to determine whether OCT differentiates the composite structural layers and inherent anatomical variations along different airway locations. The data show that OCT can clearly display the multilayered structure of the airways. The subtle architectural differences in three separate anatomical locations including trachea, main bronchus and tertiary bronchus were clearly delineated. Images of the appropriate anatomical profiles, with depth of up to 2 mm and 10 µm spatial resolution were obtained by our current OCT system, which was sufficient for recognition of the epithelium, subepithelial tissues and cartilage. In addition, the relative thickness of individual structural components was accurately reflected and comparable to histological sections. These data support OCT as a highly feasible, optical biopsy tool, which merits further exploration for early diagnosis of human airway epithelial pathology.

Disorder and function: a review of the dehydrin protein family

PubMed Central

Graether, Steffen P.; Boddington, Kelly F.

2014-01-01

Dehydration proteins (dehydrins) are group 2 members of the late embryogenesis abundant (LEA) protein family. The protein architecture of dehydrins can be described by the presence of three types of conserved sequence motifs that have been named the K-, Y-, and S-segments. By definition, a dehydrin must contain at least one copy of the lysine-rich K-segment. Abiotic stresses such as drought, cold, and salinity cause the upregulation of dehydrin mRNA and protein levels. Despite the large body of genetic and protein evidence of the importance of these proteins in stress response, the in vivo protective mechanism is not fully known. In vitro experimental evidence from biochemical assays and localization experiments suggests multiple roles for dehydrins, including membrane protection, cryoprotection of enzymes, and protection from reactive oxygen species. Membrane binding by dehydrins is likely to be as a peripheral membrane protein, since the protein sequences are highly hydrophilic and contain many charged amino acids. Because of this, dehydrins in solution are intrinsically disordered proteins, that is, they have no well-defined secondary or tertiary structure. Despite their disorder, dehydrins have been shown to gain structure when bound to ligands such as membranes, and to possibly change their oligomeric state when bound to ions. We review what is currently known about dehydrin sequences and their structures, and examine the various ligands that have been shown to bind to this family of proteins. PMID:25400646

Gender norms in South Africa: implications for HIV and pregnancy prevention among African and Indian women students at a South African tertiary institution.

PubMed

Mantell, Joanne E; Needham, Sarah L; Smit, Jennifer Ann; Hoffman, Susie; Cebekhulu, Queen; Adams-Skinner, Jessica; Exner, Theresa M; Mabude, Zonke; Beksinska, Mags; Stein, Zena A; Milford, Cecilia

2009-02-01

In post-Apartheid South Africa, women are constitutionally guaranteed protections and freedoms that were previously unknown to them. These freedoms may have positive implications for women's ability to negotiate sexual protection with partners and hence prevent unintended pregnancy and decrease their risk of HIV. Among tertiary institution students, who are a relatively 'privileged' group, there is little information on gender norms that might shape responses to HIV-prevention programmes. To elicit gender norms regarding women's and men's roles, condom and contraceptive use, sexual communication and sexual pleasure, we conducted 10 semi-structured focus group discussions with African and Indian female tertiary institution students in order to understand how norms might be used to buttress HIV- and pregnancy-prevention. Participants reported dramatic changes in the structure of gender norms and relations with the formal recognition of women's rights in the post-Apartheid context. These generational shifts in norms are supported by other research in South Africa. At the same time, women recognized the co-existence of traditional constructions of gender that operate to constrain women's freedom. The perceived changes that have taken place provide an entry point for intervention, particularly for reinforcing emerging gender norms that promote women's protection against unintended pregnancy and HIV/STIs.

Systematic detection of internal symmetry in proteins using CE-Symm.

PubMed

Myers-Turnbull, Douglas; Bliven, Spencer E; Rose, Peter W; Aziz, Zaid K; Youkharibache, Philippe; Bourne, Philip E; Prlić, Andreas

2014-05-29

Symmetry is an important feature of protein tertiary and quaternary structures that has been associated with protein folding, function, evolution, and stability. Its emergence and ensuing prevalence has been attributed to gene duplications, fusion events, and subsequent evolutionary drift in sequence. This process maintains structural similarity and is further supported by this study. To further investigate the question of how internal symmetry evolved, how symmetry and function are related, and the overall frequency of internal symmetry, we developed an algorithm, CE-Symm, to detect pseudo-symmetry within the tertiary structure of protein chains. Using a large manually curated benchmark of 1007 protein domains, we show that CE-Symm performs significantly better than previous approaches. We use CE-Symm to build a census of symmetry among domain superfamilies in SCOP and note that 18% of all superfamilies are pseudo-symmetric. Our results indicate that more domains are pseudo-symmetric than previously estimated. We establish a number of recurring types of symmetry-function relationships and describe several characteristic cases in detail. With the use of the Enzyme Commission classification, symmetry was found to be enriched in some enzyme classes but depleted in others. CE-Symm thus provides a methodology for a more complete and detailed study of the role of symmetry in tertiary protein structure [availability: CE-Symm can be run from the Web at http://source.rcsb.org/jfatcatserver/symmetry.jsp. Source code and software binaries are also available under the GNU Lesser General Public License (version 2.1) at https://github.com/rcsb/symmetry. An interactive census of domains identified as symmetric by CE-Symm is available from http://source.rcsb.org/jfatcatserver/scopResults.jsp]. Copyright © 2014. Published by Elsevier Ltd.

Denaturation of RNA secondary and tertiary structure by urea: simple unfolded state models and free energy parameters account for measured m-values

PubMed Central

Lambert, Dominic; Draper, David E.

2012-01-01

To investigate the mechanism by which urea destabilizes RNA structure, urea-induced unfolding of four different RNA secondary and tertiary structures was quantified in terms of an m-value, the rate at which the free energy of unfolding changes with urea molality. From literature data and our osmometric study of a backbone analog, we derived average interaction potentials (per Å2 of solvent accessible surface) between urea and three kinds of RNA surfaces: phosphate, ribose, and base. Estimates of the increases in solvent accessible surface areas upon RNA denaturation were based on a simple model of unfolded RNA as a combination of helical and single strand segments. These estimates, combined with the three interaction potentials and a term to account for urea interactions with released ions, yield calculated m-values in good agreement with experimental values (200 mm monovalent salt). Agreement was obtained only if single-stranded RNAs were modeled in a highly stacked, A form conformation. The primary driving force for urea induced denaturation is the strong interaction of urea with the large surface areas of bases that become exposed upon denaturation of either RNA secondary or tertiary structure, though urea interactions with backbone and released ions may account for up to a third of the m-value. Urea m-values for all four RNA are salt-dependent, which we attribute to an increased extension (or decreased charge density) of unfolded RNAs with increased urea concentration. The sensitivity of the urea m-value to base surface exposure makes it a potentially useful probe of the conformations of RNA unfolded states. PMID:23088364

Tb3+-cleavage assays reveal specific Mg2+ binding sites necessary to pre-fold the btuB riboswitch for AdoCbl binding

NASA Astrophysics Data System (ADS)

Choudhary, Pallavi K.; Gallo, Sofia; Sigel, Roland K. O.

2017-03-01

Riboswitches are RNA elements that bind specific metabolites in order to regulate the gene expression involved in controlling the cellular concentration of the respective molecule or ion. Ligand recognition is mostly facilitated by Mg2+ mediated pre-organization of the riboswitch to an active tertiary fold. To predict these specific Mg2+ induced tertiary interactions of the btuB riboswitch from E. coli, we here report Mg2+ binding pockets in its aptameric part in both, the ligand-free and the ligand-bound form. An ensemble of weak and strong metal ion binding sites distributed over the entire aptamer was detected by terbium(III) cleavage assays, Tb3+ being an established Mg2+ mimic. Interestingly many of the Mn+ (n = 2 or 3) binding sites involve conserved bases within the class of coenzyme B12-binding riboswitches. Comparison with the published crystal structure of the coenzyme B12 riboswitch of S. thermophilum aided in identifying a common set of Mn+ binding sites that might be crucial for tertiary interactions involved in the organization of the aptamer. Our results suggest that Mn+ binding at strategic locations of the btuB riboswitch indeed facilitates the assembly of the binding pocket needed for ligand recognition. Binding of the specific ligand, coenzyme B12 (AdoCbl), to the btuB aptamer does however not lead to drastic alterations of these Mn+ binding cores, indicating the lack of a major rearrangement within the three-dimensional structure of the RNA. This finding is strengthened by Tb3+ mediated footprints of the riboswitch's structure in its ligand-free and ligand-bound state indicating that AdoCbl indeed induces local changes rather than a global structural rearrangement.

LCS-TA to identify similar fragments in RNA 3D structures.

PubMed

Wiedemann, Jakub; Zok, Tomasz; Milostan, Maciej; Szachniuk, Marta

2017-10-23

In modern structural bioinformatics, comparison of molecular structures aimed to identify and assess similarities and differences between them is one of the most commonly performed procedures. It gives the basis for evaluation of in silico predicted models. It constitutes the preliminary step in searching for structural motifs. In particular, it supports tracing the molecular evolution. Faced with an ever-increasing amount of available structural data, researchers need a range of methods enabling comparative analysis of the structures from either global or local perspective. Herein, we present a new, superposition-independent method which processes pairs of RNA 3D structures to identify their local similarities. The similarity is considered in the context of structure bending and bonds' rotation which are described by torsion angles. In the analyzed RNA structures, the method finds the longest continuous segments that show similar torsion within a user-defined threshold. The length of the segment is provided as local similarity measure. The method has been implemented as LCS-TA algorithm (Longest Continuous Segments in Torsion Angle space) and is incorporated into our MCQ4Structures application, freely available for download from http://www.cs.put.poznan.pl/tzok/mcq/ . The presented approach ties torsion-angle-based method of structure analysis with the idea of local similarity identification by handling continuous 3D structure segments. The first method, implemented in MCQ4Structures, has been successfully utilized in RNA-Puzzles initiative. The second one, originally applied in Euclidean space, is a component of LGA (Local-Global Alignment) algorithm commonly used in assessing protein models submitted to CASP. This unique combination of concepts implemented in LCS-TA provides a new perspective on structure quality assessment in local and quantitative aspect. A series of computational experiments show the first results of applying our method to comparison of RNA 3D models. LCS-TA can be used for identifying strengths and weaknesses in the prediction of RNA tertiary structures.

Constraining the age and magnitude of uplift in the northern National Petroleum Reserve in Alaska (NPRA)-apatite fission-track analysis of samples from three wells

USGS Publications Warehouse

Houseknecht, David W.; Bird, Kenneth J.; O'Sullivan, Paul

2011-01-01

A broad, post-mid-Cretaceous uplift is defined in the northern National Petroleum Reserve in Alaska (NPRA) by regional truncation of Cretaceous strata, thermal maturity patterns, and amounts of exhumation estimated from sonic logs. Apatite fission-track (AFT) analysis of samples from three wells (South Meade No. 1, Topagoruk No. 1, and Ikpikpuk No. 1) across the eastern flank of the uplift indicates Tertiary cooling followed by Quaternary heating. Results from all three wells indicate that cooling, presumably caused by uplift and erosion, started about 75-65 Ma (latest Cretaceous-earliest Tertiary) and continued through the Tertiary Period. Data from South Meade indicate more rapid cooling after about 35-15 Ma (latest Eocene-middle Miocene) followed by a significant increase in subsurface temperature during the Quaternary, probably the result of increased heat flow. Data from Topagoruk and Ikpikpuk include subtle evidence of accelerated cooling starting in the latest Eocene-middle Miocene and possible evidence of increased temperature during the Quaternary. Subsurface temperature perturbations related to the insulating effect of permafrost may have been responsible for the Quaternary temperature increase at Topagoruk and Ikpikpuk and may have been a contributing factor at South Meade. Multiple lines of geologic evidence suggest that the magnitude of exhumation resulting from uplift and erosion is 5,000-6,500 ft at South Meade, 4,000-5,500 ft at Topagoruk, and 2,500-4,000 ft at Ikpikpuk. The results from these wells help to define the broad geometry of the uplift, which increases in magnitude from less than 1,000 ft at the Colville River delta to perhaps more than 7,000 ft along the northwestern coast of NPRA, between Point Barrow and Peard Bay. Neither the origin nor the offshore extent of the uplift, west and north of the NPRA coast, have been determined.

Developing a core outcome set for infant colic for primary, secondary and tertiary care settings: a prospective study.

PubMed

Steutel, Nina F; Benninga, Marc A; Langendam, Miranda W; Korterink, Judith J; Indrio, Flavia; Szajewska, Hania; Tabbers, Merit M

2017-05-29

Infant colic (IC) is defined as recurrent and prolonged crying without an obvious cause or evidence of failure to thrive or illness. It is a common problem with a prevalence of 5%-25%. The unknown aetiology results in a wide variety in interventions and use of heterogeneous outcome measures across therapeutic trials. Our aim was to develop a core outcome set (COS) for IC to facilitate and improve evidence synthesis. Prospective study design; primary, secondary and tertiary care. The COS was developed using a modified Delphi technique. First, healthcare professionals (HCPs) and parents of infants with IC were asked to list up to five outcomes they considered relevant in the treatment of IC. Outcomes mentioned by >10% of participants were forwarded to a shortlist. In the second round, outcomes on this shortlist were rated and prioritised. The final COS was defined in a face-to-face expert meeting of paediatricians. F of invited stakeholders (133 HCPs and 55 parents of infants with IC) completed both Delphi rounds. Duration of crying, family stress, sleeping time of infant, quality of life (of family), discomfort of infant and hospital admission/duration were rated as most important outcomes in IC, framing the final COS. The use of this COS should serve as a minimum of outcomes to be measured and reported. This will benefit evidence synthesis, by enhancing homogeneity of outcomes, and enable evaluation of success in therapeutic trials on IC. Researchers are strongly encouraged to use this COS when setting up a clinical trial in primary, secondary and/or tertiary care or performing a systematic review on IC. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The Crystal Structure of a Maxi/Mini-Ferritin Chimera Reveals Guiding Principles for the Assembly of Protein Cages

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

Cornell, Thomas A.; Srivastava, Yogesh; Jauch, Ralf

Cage proteins assemble into nanoscale structures with large central cavities. They play roles, including those as virus capsids and chaperones, and have been applied to drug delivery and nanomaterials. Furthermore, protein cages have been used as model systems to understand and design protein quaternary structure. Ferritins are ubiquitous protein cages that manage iron homeostasis and oxidative damage. Two ferritin subfamilies have strongly similar tertiary structure yet distinct quaternary structure: maxi-ferritins normally assemble into 24-meric, octahedral cages with C-terminal E-helices centered around 4-fold symmetry axes, and mini-ferritins are 12-meric, tetrahedral cages with 3-fold axes defined by C-termini lacking E-domains. To understandmore » the role E-domains play in ferritin quaternary structure, we previously designed a chimera of a maxi-ferritin E-domain fused to the C-terminus of a mini-ferritin. The chimera is a 12-mer cage midway in size between those of the maxi- and mini-ferritin. The research described herein sets out to understand (a) whether the increase in size over a typical mini-ferritin is due to a frozen state where the E-domain is flipped out of the cage and (b) whether the symmetrical preference of the E-domain in the maxi-ferritin (4-fold axis) overrules the C-terminal preference in the mini-ferritin (3-fold axis). With a 1.99 Å resolution crystal structure, we determined that the chimera assembles into a tetrahedral cage that can be nearly superimposed with the parent mini-ferritin, and that the E-domains are flipped external to the cage at the 3-fold symmetry axes.« less

Using a Strategy of "Structured Conversation" to Enhance the Quality of Tutorial Time

ERIC Educational Resources Information Center

Robinson, Stephanie

2008-01-01

This article considers the impact of a technique of structured conversation to enhance a student-centred approach to tutorial time. It is suggested that the development of such an approach can provide enhanced learning support in the current challenge of widening diversity in the learner population. Many students in modern tertiary education show…

Water-stable helical structure of tertiary amides of bicyclic β-amino acid bearing 7-azabicyclo[2.2.1]heptane. Full control of amide cis-trans equilibrium by bridgehead substitution.

PubMed

Hosoya, Masahiro; Otani, Yuko; Kawahata, Masatoshi; Yamaguchi, Kentaro; Ohwada, Tomohiko

2010-10-27

Helical structures of oligomers of non-natural β-amino acids are significantly stabilized by intramolecular hydrogen bonding between main-chain amide moieties in many cases, but the structures are generally susceptible to the environment; that is, helices may unfold in protic solvents such as water. For the generation of non-hydrogen-bonded ordered structures of amides (tertiary amides in most cases), control of cis-trans isomerization is crucial, even though there is only a small sterical difference with respect to cis and trans orientations. We have established methods for synthesis of conformationally constrained β-proline mimics, that is, bridgehead-substituted 7-azabicyclo[2.2.1]heptane-2-endo-carboxylic acids. Our crystallographic, 1D- and 2D-NMR, and CD spectroscopic studies in solution revealed that a bridgehead methoxymethyl substituent completely biased the cis-trans equilibrium to the cis-amide structure along the main chain, and helical structures based on the cis-amide linkage were generated independently of the number of residues, from the minimalist dimer through the tetramer, hexamer, and up to the octamer, and irrespective of the solvent (e.g., water, alcohol, halogenated solvents, and cyclohexane). Generality of the control of the amide equilibrium by bridgehead substitution was also examined.

Distributed cooperative control of AC microgrids

NASA Astrophysics Data System (ADS)

Bidram, Ali

In this dissertation, the comprehensive secondary control of electric power microgrids is of concern. Microgrid technical challenges are mainly realized through the hierarchical control structure, including primary, secondary, and tertiary control levels. Primary control level is locally implemented at each distributed generator (DG), while the secondary and tertiary control levels are conventionally implemented through a centralized control structure. The centralized structure requires a central controller which increases the reliability concerns by posing the single point of failure. In this dissertation, the distributed control structure using the distributed cooperative control of multi-agent systems is exploited to increase the secondary control reliability. The secondary control objectives are microgrid voltage and frequency, and distributed generators (DGs) active and reactive powers. Fully distributed control protocols are implemented through distributed communication networks. In the distributed control structure, each DG only requires its own information and the information of its neighbors on the communication network. The distributed structure obviates the requirements for a central controller and complex communication network which, in turn, improves the system reliability. Since the DG dynamics are nonlinear and non-identical, input-output feedback linearization is used to transform the nonlinear dynamics of DGs to linear dynamics. Proposed control frameworks cover the control of microgrids containing inverter-based DGs. Typical microgrid test systems are used to verify the effectiveness of the proposed control protocols.

The Globular State of the Single-Stranded RNA: Effect of the Secondary Structure Rearrangements

PubMed Central

Grigoryan, Zareh A.; Karapetian, Armen T.

2015-01-01

The mutual influence of the slow rearrangements of secondary structure and fast collapse of the long single-stranded RNA (ssRNA) in approximation of coarse-grained model is studied with analytic calculations. It is assumed that the characteristic time of the secondary structure rearrangement is much longer than that for the formation of the tertiary structure. A nonequilibrium phase transition of the 2nd order has been observed. PMID:26345143

All-atom four-body knowledge-based statistical potential to distinguish native tertiary RNA structures from nonnative folds.

PubMed

Masso, Majid

2018-09-14

Scientific breakthroughs in recent decades have uncovered the capability of RNA molecules to fulfill a wide array of structural, functional, and regulatory roles in living cells, leading to a concomitantly significant increase in both the number and diversity of experimentally determined RNA three-dimensional (3D) structures. Atomic coordinates from a representative training set of solved RNA structures, displaying low sequence and structure similarity, facilitate derivation of knowledge-based energy functions. Here we develop an all-atom four-body statistical potential and evaluate its capacity to distinguish native RNA 3D structures from nonnative folds based on calculated free energy scores. Atomic four-body nearest-neighbors are objectively identified by their occurrence as tetrahedral vertices in the Delaunay tessellations of RNA structures, and rates of atomic quadruplet interactions expected by chance are obtained from a multinomial reference distribution. Our four-body energy function, referred to as RAMP (ribonucleic acids multibody potential), is subsequently derived by applying the inverted Boltzmann principle to the frequency data, yielding an energy score for each type of atomic quadruplet interaction. Several well-known benchmark datasets reveal that RAMP is comparable with, and often outperforms, existing knowledge- and physics-based energy functions. To the best of our knowledge, this is the first study detailing an RNA tertiary structure-based multibody statistical potential and its comparative evaluation. Copyright © 2018 Elsevier Ltd. All rights reserved.

Structure of the immature HIV-1 capsid in intact virus particles at 8.8 Å resolution

NASA Astrophysics Data System (ADS)

Schur, Florian K. M.; Hagen, Wim J. H.; Rumlová, Michaela; Ruml, Tomáš; Müller, Barbara; Kräusslich, Hans-Georg; Briggs, John A. G.

2015-01-01

Human immunodeficiency virus type 1 (HIV-1) assembly proceeds in two stages. First, the 55 kilodalton viral Gag polyprotein assembles into a hexameric protein lattice at the plasma membrane of the infected cell, inducing budding and release of an immature particle. Second, Gag is cleaved by the viral protease, leading to internal rearrangement of the virus into the mature, infectious form. Immature and mature HIV-1 particles are heterogeneous in size and morphology, preventing high-resolution analysis of their protein arrangement in situ by conventional structural biology methods. Here we apply cryo-electron tomography and sub-tomogram averaging methods to resolve the structure of the capsid lattice within intact immature HIV-1 particles at subnanometre resolution, allowing unambiguous positioning of all α-helices. The resulting model reveals tertiary and quaternary structural interactions that mediate HIV-1 assembly. Strikingly, these interactions differ from those predicted by the current model based on in vitro-assembled arrays of Gag-derived proteins from Mason-Pfizer monkey virus. To validate this difference, we solve the structure of the capsid lattice within intact immature Mason-Pfizer monkey virus particles. Comparison with the immature HIV-1 structure reveals that retroviral capsid proteins, while having conserved tertiary structures, adopt different quaternary arrangements during virus assembly. The approach demonstrated here should be applicable to determine structures of other proteins at subnanometre resolution within heterogeneous environments.

Determinants of career satisfaction among pediatric hospitalists: a qualitative exploration

PubMed Central

Leyenaar, JoAnna K.; Capra, Lisa A.; O'Brien, Emily R.; Leslie, Laurel K.; Mackie, Thomas I.

2014-01-01

Objectives To characterize determinants of career satisfaction among pediatric hospitalists working in diverse practice settings, and to develop a framework to conceptualize factors influencing career satisfaction. Methods Semi-structured interviews were conducted with community and tertiary care hospitalists, using purposeful sampling to attain maximum response diversity. We employed close- and open-ended questions to assess levels of career satisfaction and its determinants. Interviews were conducted by telephone, recorded, and transcribed verbatim. Emergent themes were identified and analyzed using an inductive approach to qualitative analysis. Results A total of 30 interviews were conducted with community and tertiary care hospitalists, representing 20 hospital medicine programs and 7 Northeastern states. Qualitative analysis yielded 657 excerpts which were coded and categorized into four domains and associated determinants of career satisfaction: (i) professional responsibilities; (ii) hospital medicine program administration; (iii) hospital and healthcare systems; and (iv) career development. While community and tertiary care hospitalists reported similar levels of career satisfaction, they expressed variation in perspectives across these four domains. While the role of hospital medicine program administration was consistently emphasized by all hospitalists, community hospitalists prioritized resource availability, work schedule and clinical responsibilities while tertiary care hospitalists prioritized diversity in non-clinical responsibilities and career development. Conclusions We illustrate how hospitalists in different organizational settings prioritize both consistent and unique determinants of career satisfaction. Given associations between physician satisfaction and healthcare quality, efforts to optimize modifiable factors within this framework, at both community and tertiary care hospitals, may have broad impacts. PMID:24976348

Mechanisms for creating accommodation space during early Tertiary sedimentation in Tibet.

NASA Astrophysics Data System (ADS)

Studnicki-Gizbert, C.; Burchfiel, B. C.

2003-12-01

The Tibetan plateau is for the most part underlain by rocks of pre-Cenozoic age, a fact that has hindered the identification of Cenozoic shortening structures that can be unequivocally related to the effects of India-Asia collision. Notably, however, the Qiangtang block contains a number of small, short wavelength basins filled with terrestrial sediments of early Tertiary age. Where these basins have been well studied, sedimentation is recognized as having occurred coevally with compressional deformation. The classic treatment of compressional basins appeals to accommodation space created by the flexure of an elastic plate in response to loads created by adjacent thrust fault bound ranges. It is unlikely that the Tertiary basins of the Qiangtang block formed in this manner. The wavelength of a classically modelled flexural basin is a basically a function of the thickness of the elastic plate and the density difference between sedimentary fill and ductile material underlying the plate. Assuming a model of elastic flexure, the very small wavelengths (5 - 30km) characteristic of Qiangtang basins would then imply extremely thin (~ 1-5 km) effective elastic plate thicknesses. These very low values are difficult to reconcile with any reasonable characterization of crustal rheology. Instead, these relatively small basins likely record the creation of accommodation space created by differential uplift across the strike of folds and faults. Stratal geometries and sedimentation rates reflect the kinematics and geometries of local compressional structures and the mechanical basis for the creation of accommodation space remains uncertain. Finally, the origin of these basins makes it unlikely that early Tertiary sedimentation represents a significant fraction of the upper crust of Tibetan plateau.

β-connectin studies by small-angle x-ray scattering and single-molecule force spectroscopy by atomic force microscopy

NASA Astrophysics Data System (ADS)

Marchetti, S.; Sbrana, F.; Toscano, A.; Fratini, E.; Carlà, M.; Vassalli, M.; Tiribilli, B.; Pacini, A.; Gambi, C. M. C.

2011-05-01

The three-dimensional structure and the mechanical properties of a β-connectin fragment from human cardiac muscle, belonging to the I band, from I27 to I34, were investigated by small-angle x-ray scattering (SAXS) and single-molecule force spectroscopy (SMFS). This molecule presents an entropic elasticity behavior, associated to globular domain unfolding, that has been widely studied in the last 10 years. In addition, atomic force microscopy based SMFS experiments suggest that this molecule has an additional elastic regime, for low forces, probably associated to tertiary structure remodeling. From a structural point of view, this behavior is a mark of the fact that the eight domains in the I27-I34 fragment are not independent and they organize in solution, assuming a well-defined three-dimensional structure. This hypothesis has been confirmed by SAXS scattering, both on a diluted and a concentrated sample. Two different models were used to fit the SAXS curves: one assuming a globular shape and one corresponding to an elongated conformation, both coupled with a Coulomb repulsion potential to take into account the protein-protein interaction. Due to the predominance of the structure factor, the effective shape of the protein in solution could not be clearly disclosed. By performing SMFS by atomic force microscopy, mechanical unfolding properties were investigated. Typical sawtooth profiles were obtained and the rupture force of each unfolding domain was estimated. By fitting a wormlike chain model to each peak of the sawtooth profile, the entropic elasticity of octamer was described.

The Physiological Molecular Shape of Spectrin: A Compact Supercoil Resembling a Chinese Finger Trap.

PubMed

Brown, Jeffrey W; Bullitt, Esther; Sriswasdi, Sira; Harper, Sandra; Speicher, David W; McKnight, C James

2015-06-01

The primary, secondary, and tertiary structures of spectrin are reasonably well defined, but the structural basis for the known dramatic molecular shape change, whereby the molecular length can increase three-fold, is not understood. In this study, we combine previously reported biochemical and high-resolution crystallographic data with structural mass spectroscopy and electron microscopic data to derive a detailed, experimentally-supported quaternary structure of the spectrin heterotetramer. In addition to explaining spectrin's physiological resting length of ~55-65 nm, our model provides a mechanism by which spectrin is able to undergo a seamless three-fold extension while remaining a linear filament, an experimentally observed property. According to the proposed model, spectrin's quaternary structure and mechanism of extension is similar to a Chinese Finger Trap: at shorter molecular lengths spectrin is a hollow cylinder that extends by increasing the pitch of each spectrin repeat, which decreases the internal diameter. We validated our model with electron microscopy, which demonstrated that, as predicted, spectrin is hollow at its biological resting length of ~55-65 nm. The model is further supported by zero-length chemical crosslink data indicative of an approximately 90 degree bend between adjacent spectrin repeats. The domain-domain interactions in our model are entirely consistent with those present in the prototypical linear antiparallel heterotetramer as well as recently reported inter-strand chemical crosslinks. The model is consistent with all known physical properties of spectrin, and upon full extension our Chinese Finger Trap Model reduces to the ~180-200 nm molecular model currently in common use.

Geologic assessment of undiscovered hydrocarbon resources of the Western Oregon and Washington Province

USGS Publications Warehouse

,; Brownfield, Michael E.; Charpentier, Ronald R.; Cook, Troy A.; Klett, Timothy R.; Pollastro, Richard M.; Schenk, Christopher J.; Le, P.A.; ,

2011-01-01

The purpose of the U.S. Geological Survey (USGS) National Oil and Gas Assessment is to develop geology-based hypotheses regarding the potential for additions to oil and gas reserves in priority areas of the United States, focusing on the distribution, quantity, and availability of oil and natural gas resources. The USGS has completed an assessment of the undiscovered, technically recoverable oil and gas resources in western Oregon and Washington (USGS Western Oregon and Washington Province 5004). The province includes all of Oregon and Washington north of the Klamath Mountains and west of the crest of the Cascade Range, and extends offshore to the 3-mi limit of State waters on the west and to the International Boundary in the Straits of Juan de Fuca and Canada on the north. It measures about 450 mi north-south and 50 to 160 mi east-west, encompassing more than 51,000 mi2. The assessment of the Western Oregon and Washington Province is geology based and used the total petroleum system (TPS) concept. The geologic elements of a TPS include hydrocarbon source rocks (source rock maturation and hydrocarbon generation and migration), reservoir rocks (quality and distribution), and traps for hydrocarbon accumulation. Using these geologic criteria, two conventional and one unconventional (continuous) total petroleum systems were defined, with one assessment unit (AU) in each TPS: (1) the Cretaceous-Tertiary Composite TPS and the Western Oregon and Washington Conventional Gas AU, (2) the Tertiary Marine TPS and the Tertiary-Marine Gas AU, and (3) the Tertiary Coalbed Gas TPS and the Eocene Coalbed Gas AU, in which a cell-based methodology was used to estimate coalbed-gas resources.

[Prevalence of depressive and anxiety disorders in cardiovascular outpatients from 14 tertiary general hospitals of 5 Chinese cities].

PubMed

Li, Guo; Jiang, Ronghuan; Guo, Chengjun; Liu, Meiyan; Zhang, Lijun

2014-12-01

To explore the prevalence of depression and (or) anxiety disorders among cardiovascular outpatients of tertiary general hospitals of five Chinese cities. A hospital-based cross-sectional survey was conducted in the cardiovascular out-patient departments of 14 tertiary general hospitals in five Chinese cities. The patients aged 18 years and over were recruited consecutively, who were conscious and with informed consent, and can finish the questionnaire independently. All the subjects were screened with Hospital Anxiety Depression Scale (HADS). The subjects with HADS score of 8 and over were interviewed and diagnosed by psychiatrists using mini international neuropsychiatric interview (MINI). The physicians made the diagnosis and management without knowing the results of MINI and HADS score. Subjects who refused MINI were defined as the case of loss of follow-up. A total 2 123 subjects were included in the survey. The adjusted prevalence rate of depressive and anxiety disorder was 4.05% (86/2 123), the depressive and/or anxiety disorder was 14.27 % (303/2 123), depressive and anxiety disorder and mixed depressive or anxiety disorder was 14.37% (305/2 123) according to MINI. The adjusted prevalence of lifetime depressive and anxiety disorder was 5.37% (114/2 123), depressive and/or anxiety disorder was 16.91% (359/2 123), depressive and anxiety disorder and mixed depressive-anxiety disorder was 17.00% (361/2 123). There is a high prevalence of depressive and anxiety disorder among cardiovascular outpatients from tertiary general hospitals in China. Therefore, doctors must pay attention to this disorder and try to reduce the impact of this disorder in cardiovascular patients.

Cultural Resources Survey for the Lake Darling-Souris River Project, North Dakota (1982).

DTIC Science & Technology

1985-06-13

order, of the Sentinel Butte, Tongue River, and Cannonball Formations of the Fort Union Group of the Tertiary System, and the Hell Creek and Fox Hills...epoch domi- nated by a general cultural pattern. Unfortunately, American archaeologists have chosen to mix and match their terms for cultural periods...period as defined by Antevs (1955), the Middle Plains Archaic which matched the early Middle Prehistoric Period of Mulloy, the Late Plains Archaic which

Studies on functional foods in Japan--state of the art.

PubMed

Arai, S

1996-01-01

This paper pinpoints the "tertiary" function of foods which, different from the conventional "primary" and "secondary" functions that are related to nutrition and preference, respectively, is understood to be directly involved in the modulation of our physiological systems such as the immune, endocrine, nerve, circulatory, and digestive systems. Insights into this newly defined function are particularly important in that the intake of some physiologically functional constituents of foods could be effective in preventing diseases that may be caused by disorders in these physiological systems. Technologically, it has become feasible to design and produce physiologically functional foods (simply, functional foods) that are expected to satisfy in whole or in part a today's demand for disease prevention by eating. Such public expectations are reflected in the activation and development of systematic, large-scale studies on foods as seen in "Grant-in-Aid" research sponsored by the Ministry of Education, Science, and Culture. Meanwhile, the Ministry of Health and Welfare has initiated a policy of officially approving functional foods in terms of "foods for specified health uses" as defined by new legislation. Up to now (October 1995), 58 items have thus been approved. The first was a hypoallergenic rice product approved as of June 1, 1993. Here I discuss details of studies on rice-based functional foods. Other basic and applied studies directed toward the tertiary function, with future perspectives for functional foods, are also discussed.

Carbon and nitrogen stable isotope analysis of three types of oyster tissue in an impacted estuary

NASA Astrophysics Data System (ADS)

Piola, Richard F.; Moore, Stephanie K.; Suthers, Iain M.

2006-01-01

The stable isotope ratios of carbon ( δ13C) and nitrogen ( δ15N) of the muscle, ctenidia and viscera of the Sydney rock oyster, Saccostrea glomerata, showed the dilution and assimilation of tertiary treated sewage along an estuarine gradient. The enriched 15N values of oyster ctenidia and viscera from within 50 m of the sewage outfall indicated the use of 15N-enriched tertiary treated sewage effluent (16 ± 2.3‰) as a nutrient source. The effect of sewage nitrogen on oyster δ15N was localised, with oysters 5 km upstream and downstream of the outfall not significantly enriched. Viscera δ15N was most sensitive to sewage nutrients and δ13C significantly defined an ocean-to-estuarine gradient. High variance in isotope ratios of viscera compromised its use as an indicator of anthropogenic nutrients, and this also reduced the utility of whole-body stable isotope ratios. Ctenidia was the most useful indicator tissue of sewage discharge at the scale of this study, being consistently and significantly enriched in δ15N close to the sewage outfall and δ13C clearly defined an estuarine gradient with less internal variability than viscera. Muscle δ15N was least sensitive to sewage effluent and showed the least variability, making it more suited to investigations of anthropogenic nutrient enrichment over larger spatio-temporal scales.

The Unfolding and Refolding Reactions of Triosephosphate Isomerase from Trypanosoma Cruzi Follow Similar Pathways. Guanidinium Hydrochloride Studies

NASA Astrophysics Data System (ADS)

Vázquez-Contreras, Edgar; Pérez Hernández, Gerardo; Sánchez-Rebollar, Brenda Guadalupe; Chánez-Cárdenas, María Elena

2005-04-01

The unfolding and refolding reactions of Trypanosoma cruzi triosephosphate isomerase (TcTIM) was studied under equilibrium conditions at increasing guanidinium hydrochloride concentrations. The changes in activity intrinsic fluorescence and far-ultraviolet circular dichroism as a function of denaturant were used as a quaternary, tertiary and secondary structural probes respectively. The change in extrinsic ANS fluorescence intensity was also investigated. The results show that the transition between the homodimeric native enzyme to the unfolded monomers (unfolding), and its inverse reaction (refolding) are described by similar pathways and two equilibrium intermediates were detected in both reactions. The mild denaturant concentrations intermediate is active and contains significant amount of secondary and tertiary structures. The medium denaturant concentrations intermediate is inactive and able to bind the fluorescent dye. This intermediates are maybe related with those observed in the denaturation pattern of TIMs from other species; the results are discussed in this context.

Tertiary and Quaternary Ammonium-Phosphate Ionic Liquids as Lubricant Additives

DOE PAGES

Barnhill, William C.; Luo, Huimin; Meyer, III, Harry M; ...

2016-06-23

In this work we investigated the feasibility of five quaternary (aprotic) and four tertiary (protic) ammonium ionic liquids (ILs) with an identical organophosphate anion as lubricant antiwear additives. Viscosity, oil solubility, thermal stability, and corrosivity of the candidate ILs were characterized and correlated to the molecular structure. The protic group exhibits higher oil solubility than the aprotic group, and longer alkyl chains seem to provide better oil solubility and higher thermal stability. Selected ILs were applied as oil additives in steel-cast iron tribological tests and demonstrated promising anti-scuffing and anti-wear functionality. The thickness, nanostructure, coverage and composition of the tribofilmmore » formed by the besting performing IL were revealed by surface characterization for mechanistic understanding of the tribochemical interactions between the IL and metal surface. Results provide fundamental insights of the correlations among the molecular structure, physiochemical properties and lubricating performance for ammonium-phosphate ILs.« less

Tertiary and Quaternary Ammonium-Phosphate Ionic Liquids as Lubricant Additives

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

Barnhill, William C.; Luo, Huimin; Meyer, III, Harry M

In this work we investigated the feasibility of five quaternary (aprotic) and four tertiary (protic) ammonium ionic liquids (ILs) with an identical organophosphate anion as lubricant antiwear additives. Viscosity, oil solubility, thermal stability, and corrosivity of the candidate ILs were characterized and correlated to the molecular structure. The protic group exhibits higher oil solubility than the aprotic group, and longer alkyl chains seem to provide better oil solubility and higher thermal stability. Selected ILs were applied as oil additives in steel-cast iron tribological tests and demonstrated promising anti-scuffing and anti-wear functionality. The thickness, nanostructure, coverage and composition of the tribofilmmore » formed by the besting performing IL were revealed by surface characterization for mechanistic understanding of the tribochemical interactions between the IL and metal surface. Results provide fundamental insights of the correlations among the molecular structure, physiochemical properties and lubricating performance for ammonium-phosphate ILs.« less

Electronic polarization stabilizes tertiary structure prediction of HP-36.

PubMed

Duan, Li L; Zhu, Tong; Zhang, Qing G; Tang, Bo; Zhang, John Z H

2014-04-01

Molecular dynamic (MD) simulations with both implicit and explicit solvent models have been carried out to study the folding dynamics of HP-36 protein. Starting from the extended conformation, the secondary structure of all three helices in HP-36 was formed in about 50 ns and remained stable in the remaining simulation. However, the formation of the tertiary structure was difficult. Although some intermediates were close to the native structure, the overall conformation was not stable. Further analysis revealed that the large structure fluctuation of loop and hydrophobic core regions was devoted mostly to the instability of the structure during MD simulation. The backbone root-mean-square deviation (RMSD) of the loop and hydrophobic core regions showed strong correlation with the backbone RMSD of the whole protein. The free energy landscape indicated that the distribution of main chain torsions in loop and turn regions was far away from the native state. Starting from an intermediate structure extracted from the initial AMBER simulation, HP-36 was found to generally fold to the native state under the dynamically adjusted polarized protein-specific charge (DPPC) simulation, while the peptide did not fold into the native structure when AMBER force filed was used. The two best folded structures were extracted and taken into further simulations in water employing AMBER03 charge and DPPC for 25 ns. Result showed that introducing polarization effect into interacting potential could stabilize the near-native protein structure.

Visualizing the global secondary structure of a viral RNA genome with cryo-electron microscopy

PubMed Central

Garmann, Rees F.; Gopal, Ajaykumar; Athavale, Shreyas S.; Knobler, Charles M.; Gelbart, William M.; Harvey, Stephen C.

2015-01-01

The lifecycle, and therefore the virulence, of single-stranded (ss)-RNA viruses is regulated not only by their particular protein gene products, but also by the secondary and tertiary structure of their genomes. The secondary structure of the entire genomic RNA of satellite tobacco mosaic virus (STMV) was recently determined by selective 2′-hydroxyl acylation analyzed by primer extension (SHAPE). The SHAPE analysis suggested a single highly extended secondary structure with much less branching than occurs in the ensemble of structures predicted by purely thermodynamic algorithms. Here we examine the solution-equilibrated STMV genome by direct visualization with cryo-electron microscopy (cryo-EM), using an RNA of similar length transcribed from the yeast genome as a control. The cryo-EM data reveal an ensemble of branching patterns that are collectively consistent with the SHAPE-derived secondary structure model. Thus, our results both elucidate the statistical nature of the secondary structure of large ss-RNAs and give visual support for modern RNA structure determination methods. Additionally, this work introduces cryo-EM as a means to distinguish between competing secondary structure models if the models differ significantly in terms of the number and/or length of branches. Furthermore, with the latest advances in cryo-EM technology, we suggest the possibility of developing methods that incorporate restraints from cryo-EM into the next generation of algorithms for the determination of RNA secondary and tertiary structures. PMID:25752599

Geologic and geophysical investigations of Climax Stock intrusive, Nevada

USGS Publications Warehouse

,

1983-01-01

The Climax stock is a composite granitic intrusive of Cretaceous age, composed of quartz monzonite and granodiorite, which intrudes rocks of Paleozoic and Precambrian age. Tertiary volcanic rocks, consisting of ashflow and ash-fall tuffs, and tuffaceous sedimentary rocks overlie the sedimentary rocks and the stock. Erosion has removed much of the Tertiary volcanic rocks. Hydrothermal alteration of quartz monzonite and granodiorite is found mainly along joints and faults and varies from location to location. The Paleozoic carbonate rocks have been thermally and metasomatically altered to marble and tactite as much as 457 m (1,500 ft) from the contact with the stock, although minor discontinuous metasomatic effects are noted in all rocks out to 914 m (3,000 ft). Three major faults which define the Climax area structurally are the Tippinip, Boundary and Yucca faults. North of the junction of the Boundary and Yucca faults, the faults are collectively referred to as the Butte fault. The dominant joint sets and their average attitudes are N. 32? W., 22? NE; N. 60? W., vertical and N. 35? E., vertical. Joints in outcrop are weathered and generally open, but in subsurface, the joints are commonly filled and healed with secondary mineral s. The location of the water table and the degree of saturation of the granitic rocks are presently unknown. Measurement from drill holes indicated that depth to perched water levels ranges from 30 to 244 m (100-800 ft). Recent field investigations have shown the contact between the Pogonip marble and the granodiorite is a contact rather than a fault as previously mapped. The thickness of the weathered granodiorite is estimated to be 8 to 46 m (25 to 150 ft).

Deformation of allochthonous salt and evolution of related salt-structural systems, eastern Louisiana Gulf Coast

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

Schuster, D.C.

1996-12-31

Salt tectonics in the northern Gulf of Mexico involves both vertical diapirism and lateral silling or flow of salt into wings and tablets (sheets). Combinations of these two modes of salt deformation, concurrent with sediment loading and salt evacuation, have produced complex structures in the coastal and offshore region of southeastern Louisiana, a prolific oil and gas province. Many large growth faults and salt domes in the study area root into intra-Tertiary salt welds that were formerly occupied by allochthonous salt tablets. Two end-member structural systems involving evacuation of former tabular salt are recognized: roho systems and stepped counter-regional systems.more » Both end-member systems share a similar multi-staged evolution, including (1) initial formation of a south-leaning salt dome or wall sourced from the Jurassic salt level; (2) progressive development into a semi-tabular allochthonous salt body; and (3) subsequent loading, evacuation, and displacement of the tabular salt into secondary domes. In both systems, it is not uncommon to find salt displaced as much as 16-24 km south of its autochthonous source, connected by a horizontal salt weld to an updip, deflated counter-regional feeder. Although both end-member structural systems may originate before loading of allochthonous salt having grossly similar geometry, their final structural configurations after loading and salt withdrawal are distinctly different. Roho systems are characterized by large-displacement, listric, south-dipping growth faults that sole into intra-Tertiary salt welds marked by high-amplitude reflections continuous with residual salt masses. Salt from the former salt tablets has been loaded and squeezed laterally and downdip. Stepped counter-regional systems, in contrast, comprise large salt domes and adjacent large-displacement, north-dipping growth faults that sole into intra-Tertiary salt welds before stepping down again farther north.« less

Organizational Commitment and Nurses' Characteristics as Predictors of Job Involvement.

PubMed

Alammar, Kamila; Alamrani, Mashael; Alqahtani, Sara; Ahmad, Muayyad

2016-01-01

To predict nurses' job involvement on the basis of their organizational commitment and personal characteristics at a large tertiary hospital in Saudi Arabia. Data were collected in 2015 from a convenience sample of 558 nurses working at a large tertiary hospital in Riyadh, Saudi Arabia. A cross-sectional correlational design was used in this study. Data were collected using a structured questionnaire. All commitment scales had significant relationships. Multiple linear regression analysis revealed that the model predicted a sizeable proportion of variance in nurses' job involvement (p < 0.001). High organizational commitment enhances job involvement, which may lead to more organizational stability and effectiveness.

The Silent Canyon caldera complex: a three-dimensional model based on drill-hole stratigraphy and gravity inversion

USGS Publications Warehouse

McKee, Edwin H.; Hildenbrand, Thomas G.; Anderson, Megan L.; Rowley, Peter D.; Sawyer, David A.

1999-01-01

The structural framework of Pahute Mesa, Nevada, is dominated by the Silent Canyon caldera complex, a buried, multiple collapse caldera complex. Using the boundary surface between low density Tertiary volcanogenic rocks and denser granitic and weakly metamorphosed sedimentary rocks (basement) as the outer fault surfaces for the modeled collapse caldera complex, it is postulated that the caldera complex collapsed on steeply- dipping arcuate faults two, possibly three, times following eruption of at least two major ash-flow tuffs. The caldera and most of its eruptive products are now deeply buried below the surface of Pahute Mesa. Relatively low-density rocks in the caldera complex produce one of the largest gravity lows in the western conterminous United States. Gravity modeling defines a steep sided, cup-shaped depression as much as 6,000 meters (19,800 feet) deep that is surrounded and floored by denser rocks. The steeply dipping surface located between the low-density basin fill and the higher density external rocks is considered to be the surface of the ring faults of the multiple calderas. Extrapolation of this surface upward to the outer, or topographic rim, of the Silent Canyon caldera complex defines the upper part of the caldera collapse structure. Rock units within and outside the Silent Canyon caldera complex are combined into seven hydrostratigraphic units based on their predominant hydrologic characteristics. The caldera structures and other faults on Pahute Mesa are used with the seven hydrostratigraphic units to make a three-dimensional geologic model of Pahute Mesa using the "EarthVision" (Dynamic Graphics, Inc.) modeling computer program. This method allows graphic representation of the geometry of the rocks and produces computer generated cross sections, isopach maps, and three-dimensional oriented diagrams. These products have been created to aid in visualizing and modeling the ground-water flow system beneath Pahute Mesa.

Crustal structure beneath western and eastern Iceland from surface waves and receiver functions

USGS Publications Warehouse

Du, Z.; Foulger, G.R.; Julian, B.R.; Allen, R.M.; Nolet, G.; Morgan, W.J.; Bergsson, B.H.; Erlendsson, P.; Jakobsdottir, S.; Ragnarsson, S.; Stefansson, R.; Vogfjord, K.

2002-01-01

We determine the crustal structures beneath 14 broad-band seismic stations, deployed in western, eastern, central and southern Iceland, using surface wave dispersion curves and receiver functions. We implement a method to invert receiver functions using constraints obtained from genetic algorithm inversion of surface waves. Our final models satisfy both data sets. The thickness of the upper crust, as defined by the velocity horizon Vs = 3.7 km s-1, is fairly uniform at ???6.5-9 km beneath the Tertiary intraplate areas of western and eastern Iceland, and unusually thick at 11 km beneath station HOT22 in the far south of Iceland. The depth to the base of the lower crust, as defined by the velocity horizon Vs = 4.1 km s-1 is ???20-26 km in western Iceland and ???27-33 km in eastern Iceland. These results agree with those of explosion profiles that detect a thinner crust beneath western Iceland than beneath eastern Iceland. An earlier report of a substantial low-velocity zone beneath the Middle Volcanic Zone in the lower crust is confirmed by a similar observation beneath an additional station there. As was found in previous receiver function studies, the most reliable feature of the results is the clear division into an upper sequence that is a few kilometres thick where velocity gradients are high, and a lower, thicker sequence where velocity gradients are low. The transition to typical mantle velocities is variable, and may range from being very gradational to being relatively sharp and clear. A clear Moho, by any definition, is rarely seen, and there is thus uncertainty in estimates of the thickness of the crust in many areas. Although a great deal of seismic data are now available constraining the structures of the crust and upper mantle beneath Iceland, their geological nature is not well understood.

Solution structure of murine macrophage inflammatory protein-2.

PubMed

Shao, W; Jerva, L F; West, J; Lolis, E; Schweitzer, B I

1998-06-09

The solution structure of murine macrophage inflammatory protein-2 (MIP-2), a heparin-binding chemokine that is secreted in response to inflammatory stimuli, has been determined using two-dimensional homonuclear and heteronuclear NMR spectroscopy. Structure calculations were carried out by means of torsion-angle molecular dynamics using the program X-PLOR. The structure is based on a total of 2390 experimental restraints, comprising 2246 NOE-derived distance restraints, 44 distance restraints for 22 hydrogen bonds, and 100 torsion angle restraints. The structure is well-defined, with the backbone (N, Calpha, C) and heavy atom atomic rms distribution about the mean coordinates for residues 9-69 of the dimer being 0.57 +/- 0.16 A and 0.96 +/- 0.12 A, respectively. The N- and C-terminal residues (1-8 and 70-73, respectively) are disordered. The overall structure of the MIP-2 dimer is similar to that reported previously for the NMR structures of MGSA and IL-8 and consists of a six-stranded antiparallel beta-sheet (residue 25-29, 39-44, and 48-52) packed against two C-terminal antiparallel alpha-helices. A best fit superposition of the NMR structure of MIP-2 on the structures of MGSA, NAP-2, and the NMR and X-ray structures of IL-8 are 1.11, 1.02, 1.27, and 1.19 A, respectively, for the monomers, and 1.28, 1.10, 1.55, and 1.36 A, respectively, for the dimers (IL-8 residues 7-14 and 16-67, NAP-2 residues 25-84). At the tertiary level, the main differences between the MIP-2 solution structure and the IL-8, MGSA, and NAP-2 structures involve the N-terminal loop between residues 9-23 and the loops formed by residues 30-38 and residues 53-58. At the quaternary level, the difference between MIP-2 and IL-8, MGSA, or NAP-2 results from differing interhelical angles and separations.

Structural changes in gluten protein structure after addition of emulsifier. A Raman spectroscopy study

NASA Astrophysics Data System (ADS)

Ferrer, Evelina G.; Gómez, Analía V.; Añón, María C.; Puppo, María C.

2011-06-01

Food protein product, gluten protein, was chemically modified by varying levels of sodium stearoyl lactylate (SSL); and the extent of modifications (secondary and tertiary structures) of this protein was analyzed by using Raman spectroscopy. Analysis of the Amide I band showed an increase in its intensity mainly after the addition of the 0.25% of SSL to wheat flour to produced modified gluten protein, pointing the formation of a more ordered structure. Side chain vibrations also confirmed the observed changes.

Structure and properties of fixed joints formed by ultrasonic-assisted friction-stir welding

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

Fortuna, S. V., E-mail: s-fortuna@ispms.ru; Ivanov, K. V., E-mail: ikv@ispms.ru; Eliseev, A. A., E-mail: alan@ispms.ru

2015-10-27

This paper deals with structure and properties of aluminum alloy 7475 and its joints obtained by friction stir welding including under ultrasonic action. Microhardness measurements show that ultrasonic action increases strength properties of the joints. Optical and transmission electron microscopy reveals that this effect is related to the precipitation of tertiary coherent S-and T-phase particles.

Students' Communicative Resources in Relation to Their Conceptual Understanding--The Role of Non-Conventionalized Expressions in Making Sense of Visualizations of Protein Function

ERIC Educational Resources Information Center

Rundgren, Carl-Johan; Hirsch, Richard; Chang Rundgren, Shu-Nu; Tibell, Lena A. E.

2012-01-01

This study examines how students explain their conceptual understanding of protein function using visualizations. Thirteen upper secondary students, four tertiary students (studying chemical biology), and two experts were interviewed in semi-structured interviews. The interviews were structured around 2D illustrations of proteins and an animated…

Recent Development in Spectroscopic and Chemical Characterization of Cellulose

DTIC Science & Technology

2005-01-01

specific to the reducing end groups of the polysaccharides , confirmed the parallel alignment of molecular chains within the microfibrils in native...they include primary, secondary, and tertiary structures. And indeed, crystallographic studies of the monosaccharides and of related structures...Two approaches were adopted for this purpose. The first was based on examining the Raman spectra of polysaccharide polymers and oligomers that

Geophysical studies of the Syncline Ridge area, Nevada Test Site, Nye County, Nevada

USGS Publications Warehouse

Hoover, D.B.; Hanna, W.F.; Anderson, L.A.; Flanigan, V.J.; Pankratz, L.W.

1982-01-01

A wide variety of geophysical methods were employed to study a proposed nuclear waste site at Syncline Ridge on the Nevada Test Site, Nev. The proposed site was believed to be a relatively undisturbed synclinal structure containing a thick argillite unit of Misslsslppian age, the Eleana Formation unit J, which would be the emplacement medium. Data acquisition for the geophysical studies was constrained because of rugged topography in a block of Tipplpah Limestone overlying the central part of the proposed site. This study employed gravity, magnetic, seismic refraction and reflection, and four distinct electrical methods to try and define the structural integrity and shape of the proposed repository medium. Detailed and regional gravity work revealed complex structure at the site. Magnetics helped only in identifying small areas of Tertiary volcanic rocks because of low magnetization of the rocks. Seismic refraction assisted in identifying near surface faulting and bedrock structure. Difficulty was experienced in obtaining good quality reflection data. This implied significant structural complexity but also revealed the principal features that were supported by other data. Electrical methods were used for fault identification and for mapping of a thick argillaceous unit of the Eleana Formation in which nuclear waste was to be emplaced. The geophysical studies indicate that major faults along the axis of Syncline Ridge and on both margins have large vertical offsets displacing units so as not only to make mining difficult, but also providing potential paths for waste migration to underlying carbonate aquifers. The Eleana Formation appeared heterogeneous, which was inferred to be due to structural complexity. Only a small region in the northwest part of the study area was found to contain a thick and relatively undisturbed volume of host rock.

Geodynamics Of Mid-Tertiary Extensional Phase In Southwest Texas And Relationship With The Rio Bravo Fault

NASA Astrophysics Data System (ADS)

Le Pichon, X. T.; Husson, L.; Henry, P.

2004-12-01

Three independent sets of data lead us to conclude that gravity collapse alone cannot account for the Cenozoic evolution of the Texas margin of the GOM and that there has been since Paleocene a significant reactivation of the extension there.1) We have examined an extensive set of thermal data from wells including 2000 Reservoir temperatures offshore Texas and Louisiana. Solving for 1-D thermal and stratigraphic evolution of 166 representative wells we obtain the basal heat flow that defines the existence of a well defined anomaly centred on the Corsair Fault. The basal heat flow increases over less than 100 km from 35 mW/m2 northwest of the Corsair Fault to 55 mW/m2 on the fault. This increase is best explained by a crustal extensional episode during Upper Cenozoic as demonstrated by a simple modelization. The thermal structure results in very high temperatures at depth. The deepest wellls at 6000 m depth give a temperature larger than 200C. Below the Corsair rift, the extrapolated temperature is more than 300C at 10 000 m (6 s twt), 375C at 12.5 km (7 s twt) and close to 500C at 18.5 km (9 s twt). 2) Velocity/depth data from refraction (Ebeniro et al., 1988), from Moho inversion based on gravity and from 11s TWT seismic reflection depth sections show that the deep decollement layer is indeed very deep and very hot and that there is little if any igneous crust below the Corsair Rift. The velocity structure lead us to conclude that the major decollement that is generally identified with the Middle-Cretaceous Unconformity (MCU) and that lies at a depth of 7 s twt increasing to 9 s below the Corsair Rift plunges from 12-13 km northwest of the Corsair Fault to 18-19 km below the Corsair Rift. There the Moho is localized at 21-22km. The 3 km thick material between these two depths could potentially include the Cretaceous, Jurassic and Triassic as well as the whole igneous crust. In any case at this depth the present extrapolated temperature is about 500°C. The brittle-ductile transition at the present time is then expected to be situated within the sedimentary section and the brittle - ductile transition is probably situated between 6 and 8 s twt. The material, whatever its composition, below the main décollement in the area of the Corsair Rift must be metarmorphized and ductile.3) Field data led to the identification a major left-lateral shear zone most active during the late Eocene-Oligocene that we have called the Rio Bravo Fault zone. The fault zone had been previously described in the literature as the N120° Texas lineament assumed to have been inherited from the Jurassic opening of the Gulf of Mexico and located at the boundary between Texas and Mexico, approximately coinciding with the Rio Bravo (or Rio Grande).We demonstrate that this zone of shear was active during Oligocene from about 31°N to about 25°N. We conclude that an approximately 1000 km long left-lateral shear zone was active during mid-Tertiary with a total offset of 40-60 km. Its activity affected the Tertiary depocenters in Texas and within the Burgos Basin. It could account for the Paleocene to Oligocene extension in Southwest Texas.

Efficient Ligation of the Schistosoma Hammerhead Ribozyme †

PubMed Central

Canny, Marella D.; Jucker, Fiona M.; Pardi, Arthur

2011-01-01

The hammerhead ribozyme from Schistosoma mansoni is the best characterized of the natural hammerhead ribozymes. Biophysical, biochemical, and structural studies have shown that the formation of the loop-loop tertiary interaction between stems I and II alters the global folding, cleavage kinetics, and conformation of the catalytic core of this hammerhead, leading to a ribozyme that is readily cleaved under physiological conditions. This study investigates the ligation kinetics and the internal equilibrium between cleavage and ligation for the Schistosoma hammerhead. Single turnover kinetic studies on a construct where the ribozyme cleaves and ligates substrate(s) in trans showed up to 23% ligation when starting from fully cleaved products. This was achieved by a ~2,000-fold increase in the rate of ligation compared to a minimal hammerhead without the loop-loop tertiary interaction, yielding an internal equilibrium that ranges from 2–3 at physiological Mg2+ ion concentrations (0.1 –1 mM). Thus, the natural Schistosoma hammerhead ribozyme is almost as efficient at ligation as it is at cleavage. The results here are consistent with a model where formation of the loop-loop tertiary interaction leads to a higher population of catalytically active molecules, and where formation of this tertiary interaction has a much larger effect on the ligation than the cleavage activity of the Schistosoma hammerhead ribozyme. PMID:17319693

The desirable qualities of future doctors--a study of medical student perceptions.

PubMed

Hurwitz, Steven; Kelly, Brian; Powis, David; Smyth, Robyn; Lewin, Terry

2013-07-01

There is a lack of consensus regarding the qualities possessed by the ideal doctor, and very limited research regarding the views of medical students on these qualities. To investigate the views of commencing medical students regarding the desirable qualities of doctors. A survey containing a set of proposed desirable qualities of doctors identified from the existing literature was completed by 158 first-year medical students. The survey had a 75% response rate. Students rated the individual qualities of empathy, motivation to be a doctor, good verbal communication, ethically sound, integrity and honesty as the most important. A factor analysis identified six categories of qualities: methodical processing, cognitive capacity, people skills, generic work ethic, role certainty and warmth. Significant differences in factor scores were found across subgroups of students (international and domestic students, with and without prior tertiary studies) on the following factors: methodical processing, which was scored highest by domestic students with prior tertiary studies, cognitive capacity, which was scored highest by domestic students without prior tertiary studies and generic work ethic, which was scored highest by international students. Medical students identified a range of desirable personal qualities of a doctor which varied according to student characteristics, including their prior educational experience. Future research aiming to define such desirable qualities should include a broader range of stakeholders, including students at different training levels and institutions.

The evolution of the River Nile. The buried saline rift lakes in Sudan—I. Bahr El Arab Rift, the Sudd buried saline lake

NASA Astrophysics Data System (ADS)

Salama, Ramsis B.

The River Nile in Sudan, was during the Tertiary, a series of closed lake basins. Each basin occupying one of the major Sudanese rift systems (Salama, 1985a). In this paper evidence is presented for the presence of the buried saline Sudd Lake in Bahr El Arab rift. The thick Tertiary sediments filling the deep grabens were eroded from the elevated blocks; Jebel Marra, Darfur Dome, Nuba Mountains and the Nile-Congo Divide. The thick carbonate deposits existing at the faulted boundaries of Bahr El Arab defines the possible boundaries between the fresh and saline water bodies. The widespread presence of kanker nodules in the sediments was a result of continuous efflorescence, leaching and evaporative processes. The highly saline zone in the central part of the Sudd was formed through the same processes with additional sulphate being added by the oxidation of the hydrogen sulphide gases emanating from the oil fields.

Identification of phosphates involved in catalysis by the ribozyme RNase P RNA.

PubMed Central

Harris, M E; Pace, N R

1995-01-01

The RNA subunit of ribonuclease P (RNase P RNA) is a catalytic RNA that cleaves precursor tRNAs to generate mature tRNA 5' ends. Little is known concerning the identity and arrangement of functional groups that constitute the active site of this ribozyme. We have used an RNase P RNA-substrate conjugate that undergoes rapid, accurate, and efficient self-cleavage in vitro to probe, by phosphorothioate modification-interference, functional groups required for catalysis. We identify four phosphate oxygens where substitution by sulfur significantly reduces the catalytic rate (50-200-fold). Interference at one site was partially rescued in the presence of manganese, suggesting a direct involvement in binding divalent metal ion cofactors required for catalysis. All sites are located in conserved sequence and secondary structure, and positioned adjacent to the substrate phosphate in a tertiary structure model of the ribozyme-substrate complex. The spatial arrangement of phosphorothioate-sensitive sites in RNase P RNA was found to resemble the distribution of analogous positions in the secondary and potential tertiary structures of other large catalytic RNAs. PMID:7585250

Structure-activity relationships in the fusion of small unilamellar phosphatidylcholine vesicles induced by a model peptide.

PubMed

da Costa, M H; Chaimovich, H

1997-09-01

Limited proteolysis of fatty acid-free bovine serum albumin by pepsin yields several well characterized peptides, one of which (P9, M(r) 9,000), induces fusion of small unilamellar vesicles (SUV) of phosphatidylcholine at pH 3.6. Circular dichroism (CD) of P9 solutions confirmed that the peptide undergoes a reversible transition between pH 7 and pH 3.6. The spectral changes observed with CD suggest that in the low pH conformation there is a decrease in the alpha-helical contents and an exposure of hydrophobic residues. CD and differential ultraviolet spectroscopy demonstrated that P9 binds to micelles of hexadecylphosphorylcholine and the binding produces changes in the tertiary structure of the peptide. Reduction and carboxymethylation of the two disulfide bridges of P9 produced loss of the ability to induce fusion of SUV, although the reduced peptide binds to vesicles, induces loss of entrapped marker and produces vesicle disruption. In the active form P9 exposes hydrophobic groups, one amphiphilic alpha-helix and requires the integrity of the disulfide bridge-stabilized tertiary structure.

Geology of the Attaka oil field, East Kalimantan, Indonesia

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

Schwartz, C.M.; Laughbaum, G.H. Jr.; Samsu, B.S.

1973-11-01

The Attaka field is the first commercial offshore oil field to be discovered in Kalimantan, Indonesia. After its discovery in 1970 and the drilling of confirmation wells during 1970 and 1971, a development program involving 50 wells from 6 platforms was begun. The field is 12 miles off shore from the E. Kalimantan coast in 200 ft of water. Areal and vertical closures of the Attaka structure are 26 sq miles and 600 ft, respectively, and the areal extent of oil accumulation is some 9.8 sq miles. The Attaka structure is located in the Tertiary Kutei Basin which contains earlymore » Tertiary to Quaternary sediments, and the oil in the Attaka field is in numerous deltaic sands deposited during a late Miocene advance of the ancestral Mahakam River delta. Seismic velocity and well velocity survey data indicate the presence of a low velocity region more or less coincident with the limits of oil and gas accumulation on the crest of the Attaka structure. Gravity of the Attaka oil ranges from 35' to 43' API and its sulfur content is 0.1% by wt.« less

The Heidelberg Basin Drilling Project - Sedimentology and Stratigraphy of the Quaternary succession

NASA Astrophysics Data System (ADS)

Ellwanger, Dietrich; Gabriel, Gerald; Hahne, Jürgen; Hoselmann, Christian; Menzies, John; Simon, Theo; Weidenfeller, Michael; Wielandt-Schuster, Ulrike

2010-05-01

Within the context of the Heidelberg Basin Drilling Project (Gabriel et al. 2008), a detailed sediment succession is presented here based upon deep drillings taken at Heidelberg UniNord and Mannheim Käfertal. Sediment structures, and micromorphological and pollen analyses were conducted and used to reconsider some of the climate transitions within the lower Pleistocene. A new and novel scenario is postulated regarding the preservation of Quaternary sediment packages within the Cenozoic Graben environment of the Heidelberg basin. The palynological evidence comprises the periods of warm climate of the Holsteinian (mainly Abies (fir), some Fagus (beech), Pterocarya & Azolla); the Cromerian (Pinus-Picea-QM (pine-spruce-QM)); the Bavelian (Abies, Tsuga (hemlock fir), QM & phases of increased NAP including Pinus); the Waalian (Abies, Tsuga, QM); and the Tiglian (Fagus & early Pleistocene taxa especially Sciadopytis, downward increasing Tertiary taxa). The sediment package was studied both macroscopically and microscopically. Both techniques provide evidence of fluvial, lacustrine and mass movement sedimentary processes. Some include evidence of periglacial processes (silt droplets within fine grained sands indicative of frozen ground conditions). The periglacial structures are often, not always, accompanied by pollen spectra dominated by pine and NAP. E.g. the Tiglian part of the succession shows periglacial sediment structures at its base and top but not in its middle sections. I.e. it appears not as a series of warm and cold phases but rather as a constant warm period with warm-cold-alternations at its bottom and top. All results illustrate sediment preservation in the Heidelberg basin almost throughout the Quaternary. This may be due to tectonic subsidence, but also to compaction by sediment loading of underlying fine sediments (Oligocene to Quaternary) leading to incomplete but virtually continuous sediment preservation (Tanner et al. 2009). References Gabriel, G., Ellwanger, D., Hoselmann, C. & Weidenfeller, M. (2008): The Heidelberg Basin Drilling Project. - Eiszeitalter u. Gegenwart (Quaternary Science Journal), 57, 3-4, 253-260, Hannover. Tanner, D.C., Martini, N., Buness, H. & Krawczyk, C.M. (2009): The 3D Geometry of the Quaternary and Tertiary strata in the Heidelberg Basin, as defined by reflection seismics. - DGG Tagung, Dresden, 30.9-02.10.09, Schriftenreihe der Deutschen Gesellschaft für Geowissenschaften, 63, 58.

Extensional faulting in the southern Klamath Mountains, California

USGS Publications Warehouse

Schweickert, R.A.; Irwin, W.P.

1989-01-01

Large northeast striking normal faults in the southern Klamath Mountains may indicate that substantial crustal extension occurred during Tertiary time. Some of these faults form grabens in the Jurassic and older bedrock of the province. The grabens contain continental Oligocene or Miocene deposits (Weaverville Formation), and in two of them the Oligocene or Miocene is underlain by Lower Cretaceous marine formations (Great Valley sequence). At the La Grange gold placer mine the Oligocene or Miocene strata dip northwest into the gently southeast dipping mylonitic footwall surface of the La Grange fault. The large normal displacement required by the relations at the La Grange mine is also suggested by omission of several kilometers of structural thickness of bedrock units across the northeast continuation of the La Grange fault, as well as by significant changes in bedrock across some northeast striking faults elsewhere in the Central Metamorphic and Eastern Klamath belts. The Trinity ultramafic sheet crops out in the Eastern Klamath terrane as part of a broad northeast trending arch that may be structurally analogous to the domed lower plate of metamorphic core complexes found in eastern parts of the Cordillera. The northeast continuation of the La Grange fault bounds the southeastern side of the Trinity arch in the Eastern Klamath terrane and locally cuts out substantial lower parts of adjacent Paleozoic strata of the Redding section. Faults bounding the northwestem side of the Trinity arch generally trend northeast and juxtapose stacked thrust sheets of lower Paleozoic strata of the Yreka terrane against the Trinity ultramafic sheet. Geometric relations suggest that the Tertiary extension of the southern Klamath Mountains was in NW-SE directions and that the Redding section and the southern part of the Central Metamorphic terrane may be a large Tertiary allochthon detached from the Trinity ultramafic sheet. Paleomagnetic data indicate a lack of rotation about a vertical axis during the extension. We propose that the Trinity ultramafic sheet is structurally analogous to a metamorphic core complex; if so, it is the first core complex to be described that involves ultramafic rocks. We infer that Mesozoic terrane accretion produced a large gravitational instability in the crust that spread laterally during Tertiary extension

RNA secondary structure prediction with pseudoknots: Contribution of algorithm versus energy model.

PubMed

Jabbari, Hosna; Wark, Ian; Montemagno, Carlo

2018-01-01

RNA is a biopolymer with various applications inside the cell and in biotechnology. Structure of an RNA molecule mainly determines its function and is essential to guide nanostructure design. Since experimental structure determination is time-consuming and expensive, accurate computational prediction of RNA structure is of great importance. Prediction of RNA secondary structure is relatively simpler than its tertiary structure and provides information about its tertiary structure, therefore, RNA secondary structure prediction has received attention in the past decades. Numerous methods with different folding approaches have been developed for RNA secondary structure prediction. While methods for prediction of RNA pseudoknot-free structure (structures with no crossing base pairs) have greatly improved in terms of their accuracy, methods for prediction of RNA pseudoknotted secondary structure (structures with crossing base pairs) still have room for improvement. A long-standing question for improving the prediction accuracy of RNA pseudoknotted secondary structure is whether to focus on the prediction algorithm or the underlying energy model, as there is a trade-off on computational cost of the prediction algorithm versus the generality of the method. The aim of this work is to argue when comparing different methods for RNA pseudoknotted structure prediction, the combination of algorithm and energy model should be considered and a method should not be considered superior or inferior to others if they do not use the same scoring model. We demonstrate that while the folding approach is important in structure prediction, it is not the only important factor in prediction accuracy of a given method as the underlying energy model is also as of great value. Therefore we encourage researchers to pay particular attention in comparing methods with different energy models.

Effect of homogenization and pasteurization on the structure and stability of whey protein in milk.

PubMed

Qi, Phoebe X; Ren, Daxi; Xiao, Yingping; Tomasula, Peggy M

2015-05-01

The effect of homogenization alone or in combination with high-temperature, short-time (HTST) pasteurization or UHT processing on the whey fraction of milk was investigated using highly sensitive spectroscopic techniques. In pilot plant trials, 1-L quantities of whole milk were homogenized in a 2-stage homogenizer at 35°C (6.9 MPa/10.3 MPa) and, along with skim milk, were subjected to HTST pasteurization (72°C for 15 s) or UHT processing (135°C for 2 s). Other whole milk samples were processed using homogenization followed by either HTST pasteurization or UHT processing. The processed skim and whole milk samples were centrifuged further to remove fat and then acidified to pH 4.6 to isolate the corresponding whey fractions, and centrifuged again. The whey fractions were then purified using dialysis and investigated using the circular dichroism, Fourier transform infrared, and Trp intrinsic fluorescence spectroscopic techniques. Results demonstrated that homogenization combined with UHT processing of milk caused not only changes in protein composition but also significant secondary structural loss, particularly in the amounts of apparent antiparallel β-sheet and α-helix, as well as diminished tertiary structural contact. In both cases of homogenization alone and followed by HTST treatments, neither caused appreciable chemical changes, nor remarkable secondary structural reduction. But disruption was evident in the tertiary structural environment of the whey proteins due to homogenization of whole milk as shown by both the near-UV circular dichroism and Trp intrinsic fluorescence. In-depth structural stability analyses revealed that even though processing of milk imposed little impairment on the secondary structural stability, the tertiary structural stability of whey protein was altered significantly. The following order was derived based on these studies: raw whole>HTST, homogenized, homogenized and pasteurized>skimmed and pasteurized, and skimmed UHT>homogenized UHT. The methodology demonstrated in this study can be used to gain insight into the behavior of milk proteins when processed and provides a new empirical and comparative approach for analyzing and assessing the effect of processing schemes on the nutrition and quality of milk and dairy product without the need for extended separation and purification, which can be both time-consuming and disruptive to protein structures. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Geometry at the aliphatic tertiary carbon atom: computational and experimental test of the Walsh rule.

PubMed

Böhm, Stanislav; Exner, Otto

2004-02-01

The geometrical parameters of molecules of 2-substituted 2-methylpropanes and 1-substituted bicyclo[2.2.2]octanes were calculated at the B3LYP/6-311+G(d,p) level. They agreed reasonably well with the mean crystallographic values retrieved from the Cambridge Structural Database for a set of diverse non-cyclic structures with a tertiary C atom. The angle deformations at this C atom produced by the immediately bonded substituent are also closely related to those observed previously in benzene mono derivatives (either as calculated or as derived from crystallographic data). The calculated geometrical parameters were used to test the classical Walsh rule: It is evidently true that an electron-attracting substituent increases the proportion of C-atom p-electrons in the bond to the substituent and leaves more s-electrons to the remaining bonds; as a consequence the C-C-C angles at a tertiary carbon are widened and the C-C bonds shortened. However, this rule describes only part of the reality since the bond angles and lengths are controlled by other factors as well, for instance by steric crowding. Another imperfection of the Walsh rule is that the sequence of substituents does not correspond to their electronegativities, as measured by any known scale; more probably it is connected with the inductive effect, but then only very roughly.

The structure of a Mesozoic basin beneath the Lake Tana area, Ethiopia, revealed by magnetotelluric imaging

NASA Astrophysics Data System (ADS)

Hautot, Sophie; Whaler, Kathryn; Gebru, Workneh; Desissa, Mohammednur

2006-03-01

The northwestern Plateau of Ethiopia is almost entirely covered with extensive Tertiary continental flood basalts that mask the underlying formations. Mesozoic and Tertiary sediments are exposed in a few locations surrounding the Lake Tana area suggesting that the Tana depression is an extensional basin buried by the 1-2 km thick Eocene-Oligocene flood basalt sequences in this region. A magnetotelluric survey has been carried out to investigate the deep structure of the Tana area. The objectives were to estimate the thickness of the volcanics and anticipated underlying sedimentary basin. We have collected 27 magnetotelluric soundings south and east of Lake Tana. Two-dimensional inversion of the data along a 160 km long profile gives a model consistent with a NW-SE trending sedimentary basin beneath the lava flows. The thickness of sediments overlying the Precambrian basement averages 1.5-2 km, which is comparable to the Blue Nile stratigraphic section, south of the area. A 1 km thickening of sediments over a 30-40 km wide section suggests that the form of the basin is a half-graben. It is suggested that electrically resistive features in the model are related to volcanic materials intruded within the rift basin sediments through normal faults. The results illustrate the strong control of the Precambrian fracture zones on the feeding of the Tertiary Trap series.

Biotransformation of Two Pharmaceuticals by the Ammonia-Oxidizing Archaeon Nitrososphaera gargensis.

PubMed

Men, Yujie; Han, Ping; Helbling, Damian E; Jehmlich, Nico; Herbold, Craig; Gulde, Rebekka; Onnis-Hayden, Annalisa; Gu, April Z; Johnson, David R; Wagner, Michael; Fenner, Kathrin

2016-05-03

The biotransformation of some micropollutants has previously been observed to be positively associated with ammonia oxidation activities and the transcript abundance of the archaeal ammonia monooxygenase gene (amoA) in nitrifying activated sludge. Given the increasing interest in and potential importance of ammonia-oxidizing archaea (AOA), we investigated the capabilities of an AOA pure culture, Nitrososphaera gargensis, to biotransform ten micropollutants belonging to three structurally similar groups (i.e., phenylureas, tertiary amides, and tertiary amines). N. gargensis was able to biotransform two of the tertiary amines, mianserin (MIA) and ranitidine (RAN), exhibiting similar compound specificity as two ammonia-oxidizing bacteria (AOB) strains that were tested for comparison. The same MIA and RAN biotransformation reactions were carried out by both the AOA and AOB strains. The major transformation product (TP) of MIA, α-oxo MIA was likely formed via a two-step oxidation reaction. The first hydroxylation step is typically catalyzed by monooxygenases. Three RAN TP candidates were identified from nontarget analysis. Their tentative structures and possible biotransformation pathways were proposed. The biotransformation of MIA and RAN only occurred when ammonia oxidation was active, suggesting cometabolic transformations. Consistently, a comparative proteomic analysis revealed no significant differential expression of any protein-encoding gene in N. gargensis grown on ammonium with MIA or RAN compared with standard cultivation on ammonium only. Taken together, this study provides first important insights regarding the roles played by AOA in micropollutant biotransformation.

Gender norms in South Africa: Implications for HIV and pregnancy prevention among African and Indian women students at a South African tertiary institution

PubMed Central

Mantell, Joanne E.; Needham, Sarah L.; Smit, Jennifer Ann; Hoffman, Susie; Cebekhulu, Queen; Adams-Skinner, Jessica; Exner, Theresa M.; Mabude, Zonke; Beksinska, Mags; Stein, Zena A.; Milford, Cecilia

2009-01-01

In post-Apartheid South Africa, women are constitutionally guaranteed protections and freedoms that were previously unknown to them. These freedoms may have positive implications for women’s ability to negotiate sexual protection with partners and hence prevent unintended pregnancy and decrease their risk of HIV. Among tertiary institution students who are a relatively ‘privileged’ group, there is little information on gender norms that might shape responses to HIV prevention programmes. To elicit gender norms regarding women’s and men’s roles, condom and contraceptive use, sexual communication, and sexual pleasure, we conducted 10 semi-structured focus group discussions with African and Indian female tertiary institution students so as to understand how norms might be used to buttress HIV and pregnancy prevention. Participants reported dramatic changes in the structure of gender norms and relations with the formal recognition of women’s rights in the post-Apartheid context. These generational shifts in norms are supported by other research in South Africa. At the same time, women recognized the co-existence of traditional constructions of gender that operate to constrain women’s freedom. The perceived changes that have taken place provide an entry point for intervention, particularly for reinforcing emerging gender norms that promote women’s protection against unintended pregnancy and HIV/STIs. PMID:19247859

Management Information in Tertiary Institutions.

ERIC Educational Resources Information Center

Findlay, A. W.

1981-01-01

A college or university's management information system corresponds roughly to the institution's structure, with these elements in descending order in the hierarchy: policy and planning, a planning system, control and coordination, and typical operating systems (payroll, exams, scheduling, library, facilities assignments, and accounting…

The K-turn motif in riboswitches and other RNA species☆

PubMed Central

Lilley, David M.J.

2014-01-01

The kink turn is a widespread structure motif that introduces a tight bend into the axis of duplex RNA. This generally functions to mediate tertiary interactions, and to serve as a specific protein binding site. K-turns or closely related structures are found in at least seven different riboswitch structures, where they function as key architectural elements that help generate the ligand binding pocket. This article is part of a Special Issue entitled: Riboswitches. PMID:24798078

The role of atomic level steric effects and attractive forces in protein folding.

PubMed

Lammert, Heiko; Wolynes, Peter G; Onuchic, José N

2012-02-01

Protein folding into tertiary structures is controlled by an interplay of attractive contact interactions and steric effects. We investigate the balance between these contributions using structure-based models using an all-atom representation of the structure combined with a coarse-grained contact potential. Tertiary contact interactions between atoms are collected into a single broad attractive well between the C(β) atoms between each residue pair in a native contact. Through the width of these contact potentials we control their tolerance for deviations from the ideal structure and the spatial range of attractive interactions. In the compact native state dominant packing constraints limit the effects of a coarse-grained contact potential. During folding, however, the broad attractive potentials allow an early collapse that starts before the native local structure is completely adopted. As a consequence the folding transition is broadened and the free energy barrier is decreased. Eventually two-state folding behavior is lost completely for systems with very broad attractive potentials. The stabilization of native-like residue interactions in non-perfect geometries early in the folding process frequently leads to structural traps. Global mirror images are a notable example. These traps are penalized by the details of the repulsive interactions only after further collapse. Successful folding to the native state requires simultaneous guidance from both attractive and repulsive interactions. Copyright © 2011 Wiley Periodicals, Inc.

Global RNA Fold and Molecular Recognition for a pfl Riboswitch Bound to ZMP, a Master Regulator of One-Carbon Metabolism

DOE PAGES

Ren, Aiming; Rajashankar, Kanagalaghatta R.; Patel, Dinshaw J.

2015-06-25

ZTP, the pyrophosphorylated analog of ZMP (5- amino-4-imidazole carboxamide ribose-5'-monophosphate), was identified as an alarmone that senses 10-formyl-tetrahydroflate deficiency in bacteria. Recently, a pfl riboswitch was identified that selectively binds ZMP and regulates genes associated with purine biosynthesis and one-carbon metabolism. Here we report on the structure of the ZMP-bound Thermosinus carboxydivorans pfl riboswitch sensing domain, thereby defining the pseudoknot-based tertiary RNA fold, the binding-pocket architecture, and principles underlying ligand recognition specificity. Molecular recognition involves shape complementarity, with the ZMP 5-amino and carboxamide groups paired with the Watson-Crick edge of an invariant uracil, and the imidazole ring sandwiched between guanines,more » while the sugar hydroxyls form intermolecular hydrogen bond contacts. The burial of the ZMP base and ribose moieties, together with unanticipated coordination of the carboxamide by Mg 2+, contrasts with exposure of the 5'-phosphate to solvent. Lastly, our studies highlight the principles underlying RNA-based recognition of ZMP, a master regulator of one-carbon metabolism.« less

Global RNA Fold and Molecular Recognition for a pfl Riboswitch Bound to ZMP, a Master Regulator of One-Carbon Metabolism

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

Ren, Aiming; Rajashankar, Kanagalaghatta R.; Patel, Dinshaw J.

ZTP, the pyrophosphorylated analog of ZMP (5- amino-4-imidazole carboxamide ribose-5'-monophosphate), was identified as an alarmone that senses 10-formyl-tetrahydroflate deficiency in bacteria. Recently, a pfl riboswitch was identified that selectively binds ZMP and regulates genes associated with purine biosynthesis and one-carbon metabolism. Here we report on the structure of the ZMP-bound Thermosinus carboxydivorans pfl riboswitch sensing domain, thereby defining the pseudoknot-based tertiary RNA fold, the binding-pocket architecture, and principles underlying ligand recognition specificity. Molecular recognition involves shape complementarity, with the ZMP 5-amino and carboxamide groups paired with the Watson-Crick edge of an invariant uracil, and the imidazole ring sandwiched between guanines,more » while the sugar hydroxyls form intermolecular hydrogen bond contacts. The burial of the ZMP base and ribose moieties, together with unanticipated coordination of the carboxamide by Mg 2+, contrasts with exposure of the 5'-phosphate to solvent. Lastly, our studies highlight the principles underlying RNA-based recognition of ZMP, a master regulator of one-carbon metabolism.« less

Rapid comparison of properties on protein surface

PubMed Central

Sael, Lee; La, David; Li, Bin; Rustamov, Raif; Kihara, Daisuke

2008-01-01

The mapping of physicochemical characteristics onto the surface of a protein provides crucial insights into its function and evolution. This information can be further used in the characterization and identification of similarities within protein surface regions. We propose a novel method which quantitatively compares global and local properties on the protein surface. We have tested the method on comparison of electrostatic potentials and hydrophobicity. The method is based on 3D Zernike descriptors, which provides a compact representation of a given property defined on a protein surface. Compactness and rotational invariance of this descriptor enable fast comparison suitable for database searches. The usefulness of this method is exemplified by studying several protein families including globins, thermophilic and mesophilic proteins, and active sites of TIM β/α barrel proteins. In all the cases studied, the descriptor is able to cluster proteins into functionally relevant groups. The proposed approach can also be easily extended to other surface properties. This protein surface-based approach will add a new way of viewing and comparing proteins to conventional methods, which compare proteins in terms of their primary sequence or tertiary structure. PMID:18618695

Rapid comparison of properties on protein surface.

PubMed

Sael, Lee; La, David; Li, Bin; Rustamov, Raif; Kihara, Daisuke

2008-10-01

The mapping of physicochemical characteristics onto the surface of a protein provides crucial insights into its function and evolution. This information can be further used in the characterization and identification of similarities within protein surface regions. We propose a novel method which quantitatively compares global and local properties on the protein surface. We have tested the method on comparison of electrostatic potentials and hydrophobicity. The method is based on 3D Zernike descriptors, which provides a compact representation of a given property defined on a protein surface. Compactness and rotational invariance of this descriptor enable fast comparison suitable for database searches. The usefulness of this method is exemplified by studying several protein families including globins, thermophilic and mesophilic proteins, and active sites of TIM beta/alpha barrel proteins. In all the cases studied, the descriptor is able to cluster proteins into functionally relevant groups. The proposed approach can also be easily extended to other surface properties. This protein surface-based approach will add a new way of viewing and comparing proteins to conventional methods, which compare proteins in terms of their primary sequence or tertiary structure.

Reconnaissance geology of the Central Mastuj Valley, Chitral State, Pakistan

USGS Publications Warehouse

Stauffer, Karl W.

1975-01-01

The Mastuj Valley in Chitral State is a part of the Hindu Kush Range, and is one of the structurally most complicated areas in northern Pakistan. Sedimentary rocks ranging from at least Middle Devonian to Cretaceous, and perhaps Early Tertiary age lie between ridge-forming granodiorite intrusions and are cut by thrust faults. The thrust planes dip 10? to 40? to the north- west. Movement of the upper thrust plates has been toward the southeast relative to the lower blocks. If this area is structurally typical of the Hindu-Kush and Karakoram Ranges, then these mountains are much more tectonically disturbed than previously recorded, and suggest compression on a scale compatible with the hypothesis that the Himalayan, Karakoram, and Hindu Kush Ranges form part of a continental collision zone. The thrust faults outline two plates consisting of distinctive sedimentary rocks. The lower thrust plate is about 3,000 feet thick and consists of the isoclinally folded Upper Cretaceous to perhaps lower Tertiary Reshun Formation. It has overridden the Paleozoic metasedimentary rocks of the Chitral Slate unit. This thrust plate is, in turn, overridden by an 8,000-foot thick sequence consisting largely of Devonian to Carboniferous limestones and quartzites. A key factor in the tectonic processes has been the relatively soft and plastic lithology of the siltstone layers in the Reshun Formation which have acted as lubricants along the principal thrust faults, where they are commonly found today as fault slices and smears. The stratigraphic sequence, in the central Mastuj Valley was tentatively divided into 9 mapped units. The fossiliferous shales and carbonates of the recently defined Shogram Formation and the clastlcs of the Reshun Formation have been fitted into a sequence of sedimentary rocks that has a total thick- ness of at least 13,000 feet and ranges in age from Devonian to Neogene. Minerals of potential economic significance include antimony sulfides which have been mined elsewhere in Chitral, the tungstate, scheelite, which occurs in relatively high concentrations in heavy-mineral fractions of stream sands, and an iron-rich lateritic rock.

Geophysical Studies Based on Gravity and Seismic Data of Tule Desert, Meadow Valley Wash, and California Wash Basins, Southern Nevada

USGS Publications Warehouse

Scheirer, Daniel S.; Page, William R.; Miller, John J.

2006-01-01

Gravity and seismic data from Tule Desert, Meadow Valley Wash, and California Wash, Nevada, provide insight into the subsurface geometry of these three basins that lie adjacent to rapidly developing areas of Clark County, Nevada. Each of the basins is the product of Tertiary extension accommodated with the general form of north-south oriented, asymmetrically-faulted half-grabens. Geophysical inversion of gravity observations indicates that Tule Desert and Meadow Valley Wash basins are segmented into subbasins by shallow, buried basement highs. In this study, basement refers to pre-Cenozoic bedrock units that underlie basins filled with Cenozoic sedimentary and volcanic units. In Tule Desert, a small, buried basement high inferred from gravity data appears to be a horst whose placement is consistent with seismic reflection and magnetotelluric observations. Meadow Valley Wash consists of three subbasins separated by basement highs at structural zones that accommodated different styles of extension of the adjacent subbasins, an interpretation consistent with geologic mapping of fault traces oblique to the predominant north-south fault orientation of Tertiary extension in this area. California Wash is a single structural basin. The three seismic reflection lines analyzed in this study image the sedimentary basin fill, and they allow identification of faults that offset basin deposits and underlying basement. The degree of faulting and folding of the basin-fill deposits increases with depth. Pre-Cenozoic units are observed in some of the seismic reflection lines, but their reflections are generally of poor quality or are absent. Factors that degrade seismic reflector quality in this area are rough land topography due to erosion, deformed sedimentary units at the land surface, rock layers that dip out of the plane of the seismic profile, and the presence of volcanic units that obscure underlying reflectors. Geophysical methods illustrate that basin geometry is more complicated than would be inferred from extrapolation of surface topography and geology, and these methods aid in defining a three-dimensional framework to understand groundwater storage and flow in southern Nevada.

Preliminary Isostatic Gravity Map of Joshua Tree National Park and Vicinity, Southern California

USGS Publications Warehouse

Langenheim, V.E.; Biehler, Shawn; McPhee, D.K.; McCabe, C.A.; Watt, J.T.; Anderson, M.L.; Chuchel, B.A.; Stoffer, P.

2007-01-01

This isostatic residual gravity map is part of an effort to map the three-dimensional distribution of rocks in Joshua Tree National Park, southern California. This map will serve as a basis for modeling the shape of basins beneath the Park and in adjacent valleys and also for determining the location and geometry of faults within the area. Local spatial variations in the Earth's gravity field, after accounting for variations caused by elevation, terrain, and deep crustal structure, reflect the distribution of densities in the mid- to upper crust. Densities often can be related to rock type, and abrupt spatial changes in density commonly mark lithologic or structural boundaries. High-density basement rocks exposed within the Eastern Transverse Ranges include crystalline rocks that range in age from Proterozoic to Mesozoic and these rocks are generally present in the mountainous areas of the quadrangle. Alluvial sediments, usually located in the valleys, and Tertiary sedimentary rocks are characterized by low densities. However, with increasing depth of burial and age, the densities of these rocks may become indistinguishable from those of basement rocks. Tertiary volcanic rocks are characterized by a wide range of densities, but, on average, are less dense than the pre-Cenozoic basement rocks. Basalt within the Park is as dense as crystalline basement, but is generally thin (less than 100 m thick; e.g., Powell, 2003). Isostatic residual gravity values within the map area range from about 44 mGal over Coachella Valley to about 8 mGal between the Mecca Hills and the Orocopia Mountains. Steep linear gravity gradients are coincident with the traces of several Quaternary strike-slip faults, most notably along the San Andreas Fault bounding the east side of Coachella Valley and east-west-striking, left-lateral faults, such as the Pinto Mountain, Blue Cut, and Chiriaco Faults (Fig. 1). Gravity gradients also define concealed basin-bounding faults, such as those beneath the Chuckwalla Valley (e.g. Rotstein and others, 1976). These gradients result from juxtaposing dense basement rocks against thick Cenozoic sedimentary rocks.

Quality assessment of structure and language elements of written responses given by seven Scandinavian drug information centres.

PubMed

Reppe, Linda Amundstuen; Spigset, Olav; Kampmann, Jens Peter; Damkier, Per; Christensen, Hanne Rolighed; Böttiger, Ylva; Schjøtt, Jan

2017-05-01

The aim of this study was to identify structure and language elements affecting the quality of responses from Scandinavian drug information centres (DICs). Six different fictitious drug-related queries were sent to each of seven Scandinavian DICs. The centres were blinded for which queries were part of the study. The responses were assessed qualitatively by six clinical pharmacologists (internal experts) and six general practitioners (GPs, external experts). In addition, linguistic aspects of the responses were evaluated by a plain language expert. The quality of responses was generally judged as satisfactory to good. Presenting specific advice and conclusions were considered to improve the quality of the responses. However, small nuances in language formulations could affect the individual judgments of the experts, e.g. on whether or not advice was given. Some experts preferred the use of primary sources to the use of secondary and tertiary sources. Both internal and external experts criticised the use of abbreviations, professional terminology and study findings that was left unexplained. The plain language expert emphasised the importance of defining and explaining pharmacological terms to ensure that enquirers understand the response as intended. In addition, more use of active voice and less compressed text structure would be desirable. This evaluation of responses to DIC queries may give some indications on how to improve written responses on drug-related queries with respect to language and text structure. Giving specific advice and precise conclusions and avoiding too compressed language and non-standard abbreviations may aid to reach this goal.

A Preliminary Investigation of The Structure of Southern Yucca Flat, Massachusetts Mountain, and CP Basin, Nevada Test Site, Nevada, Based on Geophysical Modeling

USGS Publications Warehouse

Phelps, Geoffrey A.; Justet, Leigh; Moring, Barry C.; Roberts, Carter W.

2006-01-01

New gravity and magnetic data collected in the vicinity of Massachusetts Mountain and CP basin (Nevada Test Site, NV) provides a more complex view of the structural relationships present in the vicinity of CP basin than previous geologic models, helps define the position and extent of structures in southern Yucca Flat and CP basin, and better constrains the configuration of the basement structure separating CP basin and Frenchman Flat. The density and gravity modeling indicates that CP basin is a shallow, oval-shaped basin which trends north-northeast and contains ~800 m of basin-filling rocks and sediment at its deepest point in the northeast. CP basin is separated from the deeper Frenchman Flat basin by a subsurface ridge that may represent a Tertiary erosion surface at the top of the Paleozoic strata. The magnetic modeling indicates that the Cane Spring fault appears to merge with faults in northwest Massachusetts Mountain, rather than cut through to Yucca Flat basin and that the basin is downed-dropped relative to Massachusetts Mountain. The magnetic modeling indicates volcanic units within Yucca Flat basin are down-dropped on the west and supports the interpretations of Phelps and KcKee (1999). The magnetic data indicate that the only faults that appear to be through-going from Yucca Flat into either Frenchman Flat or CP basin are the faults that bound the CP hogback. In general, the north-trending faults present along the length of Yucca Flat bend, merge, and disappear before reaching CP hogback and Massachusetts Mountain or French Peak.

Supramolecular Architectures and Mimics of Complex Natural Folds Derived from Rationally Designed alpha-Helical Protein Structures

NASA Astrophysics Data System (ADS)

Tavenor, Nathan Albert

Protein-based supramolecular polymers (SMPs) are a class of biomaterials which draw inspiration from and expand upon the many examples of complex protein quaternary structures observed in nature: collagen, microtubules, viral capsids, etc. Designing synthetic supramolecular protein scaffolds both increases our understanding of natural superstructures and allows for the creation of novel materials. Similar to small-molecule SMPs, protein-based SMPs form due to self-assembly driven by intermolecular interactions between monomers, and monomer structure determines the properties of the overall material. Using protein-based monomers takes advantage of the self-assembly and highly specific molecular recognition properties encodable in polypeptide sequences to rationally design SMP architectures. The central hypothesis underlying our work is that alpha-helical coiled coils, a well-studied protein quaternary folding motif, are well-suited to SMP design through the addition of synthetic linkers at solvent-exposed sites. Through small changes in the structures of the cross-links and/or peptide sequence, we have been able to control both the nanoscale organization and the macroscopic properties of the SMPs. Changes to the linker and hydrophobic core of the peptide can be used to control polymer rigidity, stability, and dimensionality. The gaps in knowledge that this thesis sought to fill on this project were 1) the relationship between the molecular structure of the cross-linked polypeptides and the macroscopic properties of the SMPs and 2) a means of creating materials exhibiting multi-dimensional net or framework topologies. Separate from the above efforts on supramolecular architectures was work on improving backbone modification strategies for an alpha-helix in the context of a complex protein tertiary fold. Earlier work in our lab had successfully incorporated unnatural building blocks into every major secondary structure (beta-sheet, alpha-helix, loops and beta-turns) of a small protein with a tertiary fold. Although the tertiary fold of the native sequence was mimicked by the resulting artificial protein, the thermodynamic stability was greatly compromised. Most of this energetic penalty derived from the modifications present in the alpha-helix. The contribution within this thesis was direct comparison of several alpha-helical design strategies and establishment of the thermodynamic consequences of each.

Geology and ground-water resources of the northern part of the Ranegras Plain area, Yuma County, Arizona

USGS Publications Warehouse

Metzger, Donald George

1951-01-01

The Ranegras Plain area is part of the Basin and Range province in west-central Arizona. The report discusses rocks of pre-Cambrian, pre-Cambrian (?), Paleozoic (?), Mesozoic (?), Cretaceous (?), Cretaceous and Tertiary, Tertiary (?), Quaternary (?), and Quaternary age. All the Paleozoic (?) and Cretaceous (?) rocks and parts of the Mesozoic (?),Cretaceous and Tertiary, and Tertiary (?) rocks have been mapped as a unit because they are so intensely faulted that detailed mapping was not practical. Rocks older than Quaternary form the mountain ranges bordering the Ranegras Plain. Quaternary alluvium underlies the broad, gently sloping valley floor to depths of generally a few hundred feet, locally more. Well logs indicate that the underlying Tertiary (?) alluvium exceeds 1,100 feet in thickness. The structure of the area is controlled by faulting typical of the Basin and Range province, but the major faults are covered by alluvium and are inferred from topographic features. Ground water occurs in Quaternary and Tertiary (?) alluvium and the best aquifers are in sand and gravel of the Quaternary alluvium. Ground-water movement is, in general, to the northwest. Recharge to the aquifers is predominantly from stream flow resulting from heavy rains. There is also minor or unevaluated recharge from underflow from Butler Valley to the east, andsince 1948seepage from irrigation. Discharge is by pumping and by natural processes of underflow and evapotranspiration. In addition to small domestic and stock wells, only two irrigation wells, in the vicinity of Utting, are in use. No accurate data on pumpage are available. The safe yield from the ground-water reservoir may be less than 5,000 acre-feet and probably does not exceed 10,000 to 15,000 acre-feet per year. The quality of ground water ranges from permissible to unsuitable for irrigation purposes. The fluoride content is generally too high for the water to be considered satisfactory for use by young children.

Chemical Properties, Decomposition, and Methane Production of Tertiary Relict Plant Litters: Implications for Atmospheric Trace Gas Production in the Early Tertiary

NASA Astrophysics Data System (ADS)

Yavitt, J. B.; Bartella, T. M.; Williams, C. J.

2006-12-01

Throughout the early Tertiary (ca. 65-38 Ma) Taxodiaceae-dominated (redwood) wetland forests occupied the high latitudes and were circumpolar in their distribution. Many of these forests had high standing biomass with moderate primary productivity. The geographic extent and amount of Tertiary coals and fossil forests throughout Arctic Canada suggests large areas of wetland forests that may have cycled substantial quantities of carbon, particularly methane until they were replaced by cold tolerant Pinus, Picea, and Larix following climatic cooling associated with the Terminal Eocene Event. To test this hypothesis we compared physiochemical properties, decomposition, and trace gas production of litter from extant Metasequoia, Pinus, Picea, and Larix. Initial results from plantation-grown trees indicate Metasequoia litter is a better source of labile organic substrate than pinaceous litter. Metasequoia litter contained the least lignin and highest amounts of water-soluble compounds of the four litter types studied. Analysis of the lignin structure using cupric oxide oxidation indicates that Metasequoia lignin is enriched in 4'-hydroxyacetophenone and 4'- Hydroxy-3'-methoxyacetophenone relative to the pinaceous litter. In a 12-month decomposition study using litterbags, average litter mass loss was greater for Metasequoia litter (62%) compared to the pinaceous species (50%). Moreover, Metasequoia litter incubated under anoxic conditions produced nearly twice as much CO2 (ca. 4.2 umol/g.day) and CH4 (2.1 umol/g.day) as the pinaceous litter (2.4 umol/g.day for CO2; 1.2 umol/g.day for CH4). Our results support the idea of greater decomposability and palatability of Metasequoia litter as compared to Larix, Picea, or Pinus. Provided that the biochemical properties of Metasequoia have remained relatively stable through geologic time, it appears that early Tertiary Metasequoia-dominated wetland forests may have had higher microbial driven trace gas production than the Pinaceae-dominated forests that replaced them in the late Tertiary.

Protein Folding and Structure Prediction from the Ground Up: The Atomistic Associative Memory, Water Mediated, Structure and Energy Model.

PubMed

Chen, Mingchen; Lin, Xingcheng; Zheng, Weihua; Onuchic, José N; Wolynes, Peter G

2016-08-25

The associative memory, water mediated, structure and energy model (AWSEM) is a coarse-grained force field with transferable tertiary interactions that incorporates local in sequence energetic biases using bioinformatically derived structural information about peptide fragments with locally similar sequences that we call memories. The memory information from the protein data bank (PDB) database guides proper protein folding. The structural information about available sequences in the database varies in quality and can sometimes lead to frustrated free energy landscapes locally. One way out of this difficulty is to construct the input fragment memory information from all-atom simulations of portions of the complete polypeptide chain. In this paper, we investigate this approach first put forward by Kwac and Wolynes in a more complete way by studying the structure prediction capabilities of this approach for six α-helical proteins. This scheme which we call the atomistic associative memory, water mediated, structure and energy model (AAWSEM) amounts to an ab initio protein structure prediction method that starts from the ground up without using bioinformatic input. The free energy profiles from AAWSEM show that atomistic fragment memories are sufficient to guide the correct folding when tertiary forces are included. AAWSEM combines the efficiency of coarse-grained simulations on the full protein level with the local structural accuracy achievable from all-atom simulations of only parts of a large protein. The results suggest that a hybrid use of atomistic fragment memory and database memory in structural predictions may well be optimal for many practical applications.

How to Create a Navigational Wireframe in Word, With Site Map Example

EPA Pesticide Factsheets

Use Microsoft Word's graphic tools to create a wireframe: an organization chart showing the top three levels of HTML content (Home page, secondary pages, and tertiary pages). This is an important step in planning the structure of a website.

Kaltag fault, northern Yukon, Canada: Constraints on evolution of Arctic Alaska

NASA Astrophysics Data System (ADS)

Lane, Larry S.

1992-07-01

The Kaltag fault has been linked to several strike-slip models of evolution of the western Arctic Ocean. Hundreds of kilometres of Cretaceous-Tertiary displacement have been hypothesized in models that emplace Arctic Alaska into its present position by either left- or right-lateral strike slip. However, regional-scale displacement is precluded by new potential-field data. Postulated transform emplacement of Arctic Alaska cannot be accommodated by motion on the Kaltag fault or adjacent structures. The Kaltag fault of the northern Yukon is an eastward extrapolation of its namesake in west-central Alaska; however, a connection cannot be demonstrated. Cretaceous-Tertiary displacement on the Alaskan Kaltag fault is probably accommodated elsewhere.

Chronic effects of temperature and nitrate pollution on Daphnia magna: Is this cladoceran suitable for widespread use as a tertiary treatment?

PubMed

Maceda-Veiga, Alberto; Webster, Gordon; Canals, Oriol; Salvadó, Humbert; Weightman, Andrew J; Cable, Jo

2015-10-15

Effluent clarification and disinfection are major challenges in wastewater management. The cladoceran Daphnia magna has been proposed as a cost-effective and ecosystem-friendly option to clarify and disinfect secondary effluents, but its efficacy has not been fully tested under different sewage conditions. The present study explores the effects of temperature and nitrate on the efficacy of D. magna as a tertiary treatment at two different scales (individual assays and microcosms). Individual assays were employed to determine direct effects of temperature and/or nitrate on D. magna cultured in a suspension of organic matter. Using microcosms under the same environmental conditions, we explored the clearing efficacy of D. magna interacting with a natural microbial community. Individual assays revealed that D. magna mortality increased by 17% at 26 °C, 21% at >250 mg NO3(-)/l and by 60% at 26 °C and at >250 mg NO3(-)/l, and individuals displayed reduced body size, filtering rates and fecundity when compared to those at 21 °C and <40 mg NO3(-)/l. Improved performance under these conditions was also mirrored in the microcosms, with a higher density of D. magna (>100 ind/l) at 21 °C and <40 mg NO3(-)/l compared to the number (0-21 ind/l) at 26 °C and/or >250 mg NO3(-)/l. In the microcosms at 21 °C and <40 mg NO3(-)/l, turbidity and the density of bacteria, protists and micro-metazoa decreased in relation to those at 26 °C and/or >250 mg NO3(-)/l. Each treatment developed a unique and characteristic microbial assemblage, and D. magna was identified as the major driver of the community structure of protists and micro-metazoa. This enabled us to determine taxa vulnerability to D. magna grazing, and to re-define their tolerance thresholds for nitrate. In conclusion, this study increases our knowledge of how microbes respond to temperature and nitrate pollution, and highlights that D. magna efficacy as a tertiary treatment can be seriously compromised by variable environmental conditions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Magnetotelluric Data, Rainier Mesa/Shoshone Mountain, Nevada Test Site, Nevada.

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

Jackie M. Williams; Jay A. Sampson; Brian D. Rodriguez

2006-11-03

The United States Department of Energy (DOE) and the National Nuclear Security Administration (NNSA) at their Nevada Site Office (NSO) are addressing ground-water contamination resulting from historical underground nuclear testing through the Environmental Management (EM) program and, in particular, the Underground Test Area (UGTA) project. From 1951 to 1992, 828 underground nuclear tests were conducted at the Nevada Test Site northwest of Las Vegas. Most of these tests were conducted hundreds of feet above the ground-water table; however, more than 200 of the tests were near or within the water table. This underground testing was limited to specific areas ofmore » the Nevada Test Site, including Pahute Mesa, Rainier Mesa/Shoshone Mountain, Frenchman Flat, and Yucca Flat. One issue of concern is the nature of the somewhat poorly constrained pre-Tertiary geology, and its effects on ground-water flow. Ground-water modelers would like to know more about the hydrostratigraphy and geologic structure to support a hydrostratigraphic framework model that is under development for the Rainier Mesa/Shoshone Mountain Corrective Action Unit (Bechtel Nevada, 2006). During 2005, the U.S. Geological Survey (USGS), in cooperation with the DOE and NNSA-NSO, collected and processed data from twenty-six magnetotelluric (MT) and audio-magnetotelluric (AMT) sites at the Nevada Test Site. The 2005 data stations were located on and near Rainier Mesa and Shoshone Mountain to assist in characterizing the pre-Tertiary geology in those areas. These new stations extend the area of the hydrogeologic study previously conducted in Yucca Flat. This work will help refine what is known about the character, thickness, and lateral extent of pre-Tertiary confining units. In particular, a major goal has been to define the upper clastic confining unit (UCCU – late Devonian to Mississippian-age siliciclastic rocks assigned to the Eleana Formation and Chainman Shale) from the Yucca Flat area and west towards Shoshone Mountain, to Buckboard Mesa in the south, and onto Rainier Mesa in the north. Subsequent interpretation will include a three-dimensional (3-D) character analysis and a two-dimensional (2-D) resistivity model. The purpose of this report is to release the MT sounding data for the twenty-six stations shown in figure 1. No interpretation of the data is included here.« less

Structural evolution of the Chugach-Prince William terrane at the hinge of the orocline in Prince William Sound, and implications for ore deposits: A section in Geologic studies in Alaska by the U.S. Geological Survey, 1992

USGS Publications Warehouse

Haeussler, Peter J.; Nelson, Steven W.

1993-01-01

The Chugach-Prince William terrane is a Mesozoic through Tertiary accretionary complex that lies along coastal southern and southeastern Alaska. In Prince William Sound, the regional structural fabric bends about 90°, forming an orocline. Rocks at the hinge of the orocline consist of turbidites, conglomerate, and minor volcanic rocks and limestone. The structural geology in the hinge region defines a number of domains (each >15 km2) consisting of kilometer-scale tight folds. Adjacent domains may have up to a 90° difference in the strike of bedding and trend of fold axes. Four granite to tonalitic or gabbro plutons are dated or inferred to be about 35 Main age, and all were emplaced after regional folding. Base-metal sulfide mineral occurrences, barren quartz veins, and strikeslip late faults locally cut the plutons and generally strike north-south. The mineral occurrences often have a dendritic network of quartz veinlets adjacent to the mineralized zone and brecciated wall rock within the zone. Oroclinal bending, in the style of bending a bar, is consistent with the origin of the complicated domainal geometry of the structures. The Contact fault, thought by some workers to juxtapose two parts of the accretionary prism, truncates one of these 35-Ma plutons with strike-slip offset, but previous reverse motion cannot be ruled out. A magmatic source for the ore-forming fluids is consistent with the structural and mineralogical data. The north-south orientation of mineralized zones suggests that east-west extension occurred possibly during release of fluids from the plutons, which locally hydrofractured the wall rocks and allowed migration of ore-forming fluids along preexisting fractures.

Tertiary Structural studies of Myotoxin a from Crotalus viridis viridis Venom by Nuclear Magnetic Resonance

DTIC Science & Technology

1993-05-01

in real time. RMSDs were calculated only to a single structure on which the others were then superimposed. To get a pairwise listing of RMSDs, a group...to fix the chirality, minimize and anneal in 4-D (if necessary) an increasing number of residues until the entire structure is treated as one get /sym...nstr "Number of structures to create: get /sym refseq "Sequence to use: . get /sym refbmx "Bounds matrix to use: get /sym fname "Filename for written

Raman Optical Activity of Biological Molecules

NASA Astrophysics Data System (ADS)

Blanch, Ewan W.; Barron, Laurence D.

Now an incisive probe of biomolecular structure, Raman optical activity (ROA) measures a small difference in Raman scattering from chiral molecules in right- and left-circularly polarized light. As ROA spectra measure vibrational optical activity, they contain highly informative band structures sensitive to the secondary and tertiary structures of proteins, nucleic acids, viruses and carbohydrates as well as the absolute configurations of small molecules. In this review we present a survey of recent studies on biomolecular structure and dynamics using ROA and also a discussion of future applications of this powerful new technique in biomedical research.

3D Model of the McGinness Hills Geothermal Area

DOE Data Explorer

Faulds, James E.

2013-12-31

The McGinness Hills geothermal system lies in a ~8.5 km wide, north-northeast trending accommodation zone defined by east-dipping normal faults bounding the Toiyabe Range to the west and west-dipping normal faults bounding the Simpson Park Mountains to the east. Within this broad accommodation zone lies a fault step-over defined by north-northeast striking, west-dipping normal faults which step to the left at roughly the latitude of the McGinness Hills geothermal system. The McGinness Hills 3D model consists of 9 geologic units and 41 faults. The basal geologic units are metasediments of the Ordovician Valmy and Vininni Formations (undifferentiated in the model) which are intruded by Jurassic granitic rocks. Unconformably overlying is a ~100s m-thick section of Tertiary andesitic lava flows and four Oligocene-to-Miocene ash-flow tuffs: The Rattlesnake Canyon Tuff, tuff of Sutcliffe, the Cambell Creek Tuff and the Nine Hill tuff. Overlying are sequences of pre-to-syn-extensional Quaternary alluvium and post-extensional Quaternary alluvium. 10-15º eastward dip of the Tertiary stratigraphy is controlled by the predominant west-dipping fault set. Geothermal production comes from two west dipping normal faults in the northern limb of the step over. Injection is into west dipping faults in the southern limb of the step over. Production and injection sites are in hydrologic communication, but at a deep level, as the northwest striking fault that links the southern and northern limbs of the step-over has no permeability.

Hydrogen Bonded Squaramide-Based Foldable Module Induces Both β- and α-Turns in Hairpin Structures of α-Peptides in Water.

PubMed

Martínez, Luís; Martorell, Gabriel; Sampedro, Ángel; Ballester, Pablo; Costa, Antoni; Rotger, Carmen

2015-06-19

A novel tertiary squaramido-based reverse-turn module SQ is reported, and its conformational properties are evaluated. This module is easily incorporated into a α-peptide sequence by conventional solid-phase peptide synthesis. The structure characterization of the hybrid squaramido-peptide 4 is described, showing that the turn segment induces the formation of hairpin structures in water through the formation of both αSQ- and βSQ-turns.

Cold Vacuum Drying facility civil structural system design description (SYS 06)

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

PITKOFF, C.C.

This document describes the Cold Vacuum Drying (CVD) Facility civil - structural system. This system consists of the facility structure, including the administrative and process areas. The system's primary purpose is to provide for a facility to house the CVD process and personnel and to provide a tertiary level of containment. The document provides a description of the facility and demonstrates how the design meets the various requirements imposed by the safety analysis report and the design requirements document.

F-actin and G-actin binding are uncoupled by mutation of conserved tyrosine residues in maize actin depolymerizing factor (ZmADF)

PubMed Central

Jiang, Chang-Jie; Weeds, Alan G.; Khan, Safina; Hussey, Patrick J.

1997-01-01

Actin depolymerizing factors (ADF) are stimulus responsive actin cytoskeleton modulating proteins. They bind both monomeric actin (G-actin) and filamentous actin (F-actin) and, under certain conditions, F-actin binding is followed by filament severing. In this paper, using mutant maize ADF3 proteins, we demonstrate that the maize ADF3 binding of F-actin can be spatially distinguished from that of G-actin. One mutant, zmadf3–1, in which Tyr-103 and Ala-104 (equivalent to destrin Tyr-117 and Ala-118) have been replaced by phenylalanine and glycine, respectively, binds more weakly to both G-actin and F-actin compared with maize ADF3. A second mutant, zmadf3–2, in which both Tyr-67 and Tyr-70 are replaced by phenylalanine, shows an affinity for G-actin similar to maize ADF3, but F-actin binding is abolished. The two tyrosines, Tyr-67 and Tyr-70, are in the equivalent position to Tyr-82 and Tyr-85 of destrin, respectively. Using the tertiary structure of destrin, yeast cofilin, and Acanthamoeba actophorin, we discuss the implications of removing the aromatic hydroxyls of Tyr-82 and Tyr-85 (i.e., the effect of substituting phenylalanine for tyrosine) and conclude that Tyr-82 plays a critical role in stabilizing the tertiary structure that is essential for F-actin binding. We propose that this tertiary structure is maintained as a result of a hydrogen bond between the hydroxyl of Tyr-82 and the carbonyl of Tyr-117, which is located in the long α-helix; amino acid components of this helix (Leu-111 to Phe-128) have been implicated in G-actin and F-actin binding. The structures of human destrin and yeast cofilin indicate a hydrogen distance of 2.61 and 2.77 Å, respectively, with corresponding bond angles of 99.5° and 113°, close to the optimum for a strong hydrogen bond. PMID:9275236

Pediatric emergency care in europe: a descriptive survey of 53 tertiary medical centers.

PubMed

Mintegi, Santiago; Shavit, Itai; Benito, Javier

2008-06-01

To examine determinants of quality of care provided by pediatric emergency departments (PEDs) in tertiary European centers. Analysis of questionnaires was sent to directors of PEDs. Questionnaires were sent through the pediatric research group of the European Society for Emergency Medicine. Three major descriptive categories were included in a 28-point questionnaire: institution's pediatric inpatient capabilities, scope of services, and medical staff education and structure. Sixty-five questionnaires were completed in full. Fifty-three tertiary medical centers from 14 countries were included in the study. In 86.8% of these institutions, the PED is separated from the adult emergency department; 91% have a pediatric intensive care unit, and 72% have an in-patient pediatric trauma service. Eighty-eight percent of the PEDs have incorporated triage protocols. Social service was not available in 17% of the departments. Sedation for painful procedures is provided by the staff in 77% of the PEDs. Only 24% of the PED medical directors have been formally trained in pediatric emergency medicine. In 17% of the departments, there is a 24-hour 7-day residents' coverage with no attending pediatrician or pediatric emergency medicine-trained physician. According to this pilot study, the basic services provided by tertiary PEDs in Europe appear to be appropriate. Physicians training level and staffing may not be adequate to achieve optimal patient outcome.

Molecular data and ecological niche modelling reveal a highly dynamic evolutionary history of the East Asian Tertiary relict Cercidiphyllum (Cercidiphyllaceae).

PubMed

Qi, Xin-Shuai; Chen, Chen; Comes, Hans Peter; Sakaguchi, Shota; Liu, Yi-Hui; Tanaka, Nobuyuki; Sakio, Hitoshi; Qiu, Ying-Xiong

2012-10-01

East Asia's temperate deciduous forests served as sanctuary for Tertiary relict trees, but their ages and response to past climate change remain largely unknown. To address this issue, we elucidated the evolutionary and population demographic history of Cercdiphyllum, comprising species in China/Japan (Cercdiphyllum japonicum) and central Japan (Cercdiphyllum magnificum). Fifty-three populations were genotyped using chloroplast and ribosomal DNA sequences and microsatellite loci to assess molecular structure and diversity in relation to past (Last Glacial Maximum) and present distributions based on ecological niche modelling. Late Tertiary climate cooling was reflected in a relatively recent speciation event, dated at the Mio-/Pliocene boundary. During glacials, the warm-temperate C. japonicum experienced massive habitat losses in some areas (north-central China/north Japan) but increases in others (southwest/-east China, East China Sea landbridge, south Japan). In China, the Sichuan Basin and/or the middle-Yangtze were source areas of postglacial northward recolonization; in Japan, this may have been facilitated through introgressive hybridization with the cool-temperate C. magnificum. Our findings challenge the notion of relative evolutionary and demographic stability of Tertiary relict trees, and may serve as a guideline for assessing the impact of Neogene climate change on the evolution and distribution of East Asian temperate plants. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

Total petroleum systems of the Pelagian Province, Tunisia, Libya, Italy, and Malta; the Bou Dabbous, Tertiary and Jurassic-Cretaceous composite

USGS Publications Warehouse

Klett, T.R.

2001-01-01

Undiscovered conventional oil and gas resources were assessed within total petroleum systems of the Pelagian Province (2048) as part of the U.S. Geological Survey World Petroleum Assessment 2000. The Pelagian Province is located mainly in eastern Tunisia and northwestern Libya. Small portions of the province extend into Malta and offshore Italy. Although several petroleum systems may exist, only two ?composite? total petroleum systems were identified. Each total petroleum system comprises a single assessment unit. These total petroleum systems are called the Bou Dabbous?Tertiary and Jurassic-Cretaceous Composite, named after the source-rock intervals and reservoir-rock ages. The main source rocks include mudstone of the Eocene Bou Dabbous Formation; Cretaceous Bahloul, Lower Fahdene, and M?Cherga Formations; and Jurassic Nara Formation. Known reservoirs are in carbonate rocks and sandstone intervals throughout the Upper Jurassic, Cretaceous, and Tertiary sections. Traps for known accumulations include fault blocks, low-amplitude anticlines, high-amplitude anticlines associated with reverse faults, wrench fault structures, and stratigraphic traps. The estimated means of the undiscovered conventional petroleum volumes in total petroleum systems of the Pelagian Province are as follows: [MMBO, million barrels of oil; BCFG, billion cubic feet of gas; MMBNGL, million barrels of natural gas liquids] Total Petroleum System MMBO BCFG MMBNGL Bou Dabbous?Tertiary 667 2,746 64 Jurassic-Cretaceous Composite 403 2,280 27

Enhanced Product Stability in the Hammerhead Ribozyme†

PubMed Central

Shepotinovskaya, Irina; Uhlenbeck, Olke C.

2010-01-01

The rate of dissociation of P1, the 5′ product of hammerhead cleavage, is 100–300-fold slower in full-length hammerheads than in hammerheads that either lack or have disrupting mutations in the loop-loop tertiary interaction. The added stability requires the presence of residue 17 at the 3′ terminus of P1 but not the 2′, 3′ terminal phosphate. Since residue 17 is buried within the catalytic core of the hammerhead in the x-ray structure, we propose that the enhanced P1 stability is the result of the cooperative folding of the hammerhead around this residue. However, since the P1 is fully stabilized above 2.5 mM MgCl2 while hammerhead activity continues to increase with increasing MgCl2, it is clear that the hammerhead structure in the transition state must differ from that of the product complex. The product stabilization assay is used to test our earlier proposal that different tertiary interactions modulate the cleavage rate by differentially stabilizing the core. PMID:20423112

Immunoinformatic Analysis of Crimean Congo Hemorrhagic Fever Virus Glycoproteins and Epitope Prediction for Synthetic Peptide Vaccine.

PubMed

Tipu, Hamid Nawaz

2016-02-01

To determine the Crimean Congo Hemorrhagic Fever (CCHF) virus M segement glycoprotein's immunoinformatic parameters, and identify Human Leukocyte Antigen (HLA) class I binders as candidates for synthetic peptide vaccines. Cross-sectional study. Combined Military Hospital, Khuzdar Cantt, in May 2015. Data acquisition, antigenicity prediction, secondary and tertiary structure prediction, residue analysis were done using immunoinformatics tools. HLAclass I binders in glycoprotein's sequence were identified at nanomer length using NetMHC 3.4 and mapped onto tertiary structure. Docking was done for strongest binder against its corresponding allele with CABS-dock. HLAA*0101, 0201, 0301, 2402, 2601 and B*0702, 0801, 2705, 3901, 4001, 5801, 1501 were analyzed against two glycoprotein components of the virus. Atotal of 35 nanomers from GP1, and 3 from GP2 were identified. HLAB*0702 bound maximum number of peptides (6), while HLAB*4001 showed strongest binding affinity. HLAspecific glycoproteins epitope prediction can help identify synthetic peptide vaccine candidates.

Subsurface stratigraphic cross sections of cretaceous and lower tertiary rocks in the Wind River Basin, central Wyoming: Chapter 9 in Petroleum systems and geologic assessment of oil and gas resources in the Wind River Basin Province, Wyoming

USGS Publications Warehouse

Finn, Thomas M.

2007-01-01

The stratigraphic cross sections presented in this report were constructed as part of a project conducted by the U.S. Geological Survey to characterize and evaluate the undiscovered oil and gas resources of the Wind River Basin (WRB) in central Wyoming. The primary purpose of the cross sections is to show the stratigraphic framework and facies relations of Cretaceous and lower Tertiary rocks in this large, intermontane structural and sedimentary basin, which formed in the Rocky Mountain foreland during the Laramide orogeny (Late Cretaceous through early Eocene time). The WRB is nearly 200 miles (mi) long, 70 mi wide, and encompasses about 7,400 square miles (mi2) (fig. 1). The basin is structurally bounded by the Owl Creek and Bighorn Mountains on the north, the Casper arch on the east, the Granite Mountains on the south, and the Wind River Range on the west.

Physiologically based pharmacokinetic model for ethyl tertiary-butyl ether and tertiary-butyl alcohol in rats: Contribution of binding to α2u-globulin in male rats and high-exposure nonlinear kinetics to toxicity and cancer outcomes.

PubMed

Borghoff, Susan J; Ring, Caroline; Banton, Marcy I; Leavens, Teresa L

2017-05-01

In cancer bioassays, inhalation, but not drinking water exposure to ethyl tertiary-butyl ether (ETBE), caused liver tumors in male rats, while tertiary-butyl alcohol (TBA), an ETBE metabolite, caused kidney tumors in male rats following exposure via drinking water. To understand the contribution of ETBE and TBA kinetics under varying exposure scenarios to these tumor responses, a physiologically based pharmacokinetic model was developed based on a previously published model for methyl tertiary-butyl ether, a structurally similar chemical, and verified against the literature and study report data. The model included ETBE and TBA binding to the male rat-specific protein α2u-globulin, which plays a role in the ETBE and TBA kidney response observed in male rats. Metabolism of ETBE and TBA was described as a single, saturable pathway in the liver. The model predicted similar kidney AUC 0-∞ for TBA for various exposure scenarios from ETBE and TBA cancer bioassays, supporting a male-rat-specific mode of action for TBA-induced kidney tumors. The model also predicted nonlinear kinetics at ETBE inhalation exposure concentrations above ~2000 ppm, based on blood AUC 0-∞ for ETBE and TBA. The shift from linear to nonlinear kinetics at exposure concentrations below the concentration associated with liver tumors in rats (5000 ppm) suggests the mode of action for liver tumors operates under nonlinear kinetics following chronic exposure and is not relevant for assessing human risk. Copyright © 2016 The Authors Journal of Applied Toxicology Published by John Wiley & Sons Ltd. Copyright © 2016 The Authors Journal of Applied Toxicology Published by John Wiley & Sons Ltd.

Disaster content in Australian tertiary postgraduate emergency nursing courses: a survey.

PubMed

Ranse, Jamie; Shaban, Ramon Z; Considine, Julie; Hammad, Karen; Arbon, Paul; Mitchell, Belinda; Lenson, Shane

2013-05-01

Emergency nurses play a pivotal role in disaster relief during the response to, and recovery of both in-hospital and out-of-hospital disasters. Postgraduate education is important in preparing and enhancing emergency nurses' preparation for disaster nursing practice. The disaster nursing content of Australian tertiary postgraduate emergency nursing courses has not been compared across courses and the level of agreement about suitable content is not known. To explore and describe the disaster content in Australian tertiary postgraduate emergency nursing courses. A retrospective, exploratory and descriptive study of the disaster content of Australian tertiary postgraduate emergency nursing courses conducted in 2009. Course convenors from 12 universities were invited to participate in a single structured telephone survey. Data was analysed using descriptive statistics. Ten of the twelve course convenors from Australian tertiary postgraduate emergency nursing courses participated in this study. The content related to disasters was varied, both in terms of the topics covered and duration of disaster content. Seven of these courses included some content relating to disaster health, including types of disasters, hospital response, nurses' roles in disasters and triage. The management of the dead and dying, and practical application of disaster response skills featured in only one course. Three courses had learning objectives specific to disasters. The majority of courses had some disaster content but there were considerable differences in the content chosen for inclusion across courses. The incorporation of core competencies such as those from the International Council of Nurses and the World Health Organisation, may enhance content consistency in curriculum. Additionally, this content could be embedded within a proposed national education framework for disaster health. Copyright © 2013 College of Emergency Nursing Australasia Ltd. Published by Elsevier Ltd. All rights reserved.

Effects of urea induced protein conformational changes on ion exchange chromatographic behavior.

PubMed

Hou, Ying; Hansen, Thomas B; Staby, Arne; Cramer, Steven M

2010-11-19

Urea is widely employed to facilitate protein separations in ion exchange chromatography at various scales. In this work, five model proteins were used to examine the chromatographic effects of protein conformational changes induced by urea in ion exchange chromatography. Linear gradient experiments were carried out at various urea concentrations and the protein secondary and tertiary structures were evaluated by far UV CD and fluorescence measurements, respectively. The results indicated that chromatographic retention times were well correlated with structural changes and that they were more sensitive to tertiary structural change. Steric Mass Action (SMA) isotherm parameters were also examined and the results indicated that urea induced protein conformational changes could affect both the characteristic charge and equilibrium constants in these systems. Dynamic light scattering analysis of changes in protein size due to urea-induced unfolding indicated that the size of the protein was not correlated with SMA parameter changes. These results indicate that while urea-induced structural changes can have a marked effect on protein chromatographic behavior in IEX, this behavior can be quite complicated and protein specific. These differences in protein behavior may provide insight into how these partially unfolded proteins are interacting with the resin material. Copyright © 2010 Elsevier B.V. All rights reserved.

Defining and classifying medical error: lessons for patient safety reporting systems.

PubMed

Tamuz, M; Thomas, E J; Franchois, K E

2004-02-01

It is important for healthcare providers to report safety related events, but little attention has been paid to how the definition and classification of events affects a hospital's ability to learn from its experience. To examine how the definition and classification of safety related events influences key organizational routines for gathering information, allocating incentives, and analyzing event reporting data. In semi-structured interviews, professional staff and administrators in a tertiary care teaching hospital and its pharmacy were asked to describe the existing programs designed to monitor medication safety, including the reporting systems. With a focus primarily on the pharmacy staff, interviews were audio recorded, transcribed, and analyzed using qualitative research methods. Eighty six interviews were conducted, including 36 in the hospital pharmacy. Examples are presented which show that: (1) the definition of an event could lead to under-reporting; (2) the classification of a medication error into alternative categories can influence the perceived incentives and disincentives for incident reporting; (3) event classification can enhance or impede organizational routines for data analysis and learning; and (4) routines that promote organizational learning within the pharmacy can reduce the flow of medication error data to the hospital. These findings from one hospital raise important practical and research questions about how reporting systems are influenced by the definition and classification of safety related events. By understanding more clearly how hospitals define and classify their experience, we may improve our capacity to learn and ultimately improve patient safety.

Geologic assessment of undiscovered oil and gas resources in Aptian carbonates, onshore northern Gulf of Mexico Basin, United States

USGS Publications Warehouse

Hackley, Paul C.; Karlsen, Alexander W.

2014-01-01

Carbonate lithofacies of the Lower Cretaceous Sligo Formation and James Limestone were regionally evaluated using established U.S. Geological Survey (USGS) assessment methodology for undiscovered conventional hydrocarbon resources. The assessed area is within the Upper Jurassic–Cretaceous–Tertiary Composite total petroleum system, which was defined for the assessment. Hydrocarbons reservoired in carbonate platform Sligo-James oil and gas accumulations are interpreted to originate primarily from the Jurassic Smackover Formation. Emplacement of hydrocarbons occurred via vertical migration along fault systems; long-range lateral migration also may have occurred in some locations. Primary reservoir facies include porous patch reefs developed over paleostructural salt highs, carbonate shoals, and stacked linear reefs at the carbonate shelf margin. Hydrocarbon traps dominantly are combination structural-stratigraphic. Sealing lithologies include micrite, calcareous shale, and argillaceous lime mudstone. A geologic model, supported by discovery history analysis of petroleum geology data, was used to define a single regional assessment unit (AU) for conventional reservoirs in carbonate facies of the Sligo Formation and James Limestone. The AU is formally entitled Sligo-James Carbonate Platform Oil and Gas (50490121). A fully risked mean undiscovered technically recoverable resource in the AU of 50 million barrels of oil (MMBO), 791 billion cubic feet of natural gas (BCFG), and 26 million barrels of natural gas liquids was estimated. Substantial new development through horizontal drilling has occurred since the time of this assessment (2010), resulting in cumulative production of >200 BCFG and >1 MMBO.

Tectonic evolution of the Songpan Garzê and adjacent areas (NE Tibet) from Triassic to Present : a synthesis.

NASA Astrophysics Data System (ADS)

Roger, F.; Jolivet, M.; Malavieille, J.

2009-04-01

The 12th May 2008 Wenchuan earthquake in the Longmen Shan occurred on a large thrust fault largely inherited from an Indosinian structure itself probably controlled by an older structural heritage of the South China block continental margin. Within the whole northeast Tibet region, such a structural inheritance has had a major impact on the Tertiary deformation. It appears of primary importance to assess the pre-Tertiary tectonic evolution of the main blocks involved to understand the actual deformation in the eastern edge of Tibet. Over the past decades, the Proterozoic to Cenozoic tectonic, metamorphic and geochronologic history of the Longmen Shan and Songpan Garzê area have been largely studied. We present a synthesis of the tectonic evolution of the Songpan Garzê fold and thrust belt from Triassic to present. The Songpan-Garzê belt was formed during closure of a wide oceanic basin filled with a thick (5 to 15 km) sequence of Triassic flyschoid sediments [10]. Closure of the basin due to Triassic subduction involved strong shortening, intense folding and faulting of the Triassic series. A large-scale décollement, that presently outcrops along the eastern boundary of the belt (Danba area), allowed the growth of a wide and thick accretionary wedge [9]. It develops in the Paleozoic and Triassic series and separates the accretionary prism from an autochthonous crystalline basement [5, 12, 6] which shares many similarities with the basement of the Yangtze Craton (0.7-0.9 Ga). To the north and northwest, below the thickened Triassic series of the belt, the composition (oceanic or continental) of the basement remains unknown. During the Indosinian orogeny the emplacement of orogenic granites (220 - 150 Ma) was associated to crustal thickening [12, 13, 17, 15]. The isotopic composition of granitoids shows that their magma source were predominantly derived from melting of the proterozoic basement with varying degrees of sedimentary material and negligible mantle source contribution. In the Danba area, the décollement outcrops in a large tertiary antiform with a NNW-SSE axis [6, 12, 18]. It has been exhumed too in the hanging wall of the NE-SW faults of the Tertiary Longmen-Shan belt that marks the present day transition from the Tibetan plateau to the Sichuan basin. These faults have episodically absorbed significant shortening since the Late Triassic [3]. The amount and precise timing of post-triassic deformation are difficult to constrain especially because of the difficulty to isolate the tertiary thermochronological signal from the protracted late Triassic - Cretaceous thermal history (e.g. [14]). Nonetheless it is generally accepted that Jurassic - Cretaceous tectonism did not modified the general Triassic architecture of eastern Tibet contrarily to the Tertiary deformation (e.g. [2, 12, 5, 14]). The long-term cooling histories obtained on Mesozoic granites and on the metamorphic series of the Danba dome are very similar showing a very slow and regular cooling during Jurassic and Cretaceous, confirming the absence of major tectonic event between c.a. 150 and 30 Ma [16, 7, 6, 12, 18]. Low temperature thermochronology data indicate that final exhumation and cooling occurred in the Tertiary with an acceleration between 10 and 5 Ma along the major tectonic structures [11, 12, 1, 16, 7,14, 8]. Within the Longmen Shan range, a total denudation of 7 to 10 km is estimated for the late Cenozoic period [1, 7, 4]. Similar amounts of late Tertiary denudation have been estimated along an east-west section across the Xianshuihe fault [16]. 1 : Arne et al., (1997), Tectonophysics 280, 239-256. 2 : Burchfield et al. (1995), International Geology Review 37, 661-735. 3 : Chen and Wilson, (1996), Journal of Structural Geology 18, 413-440. 4 : Clark et al., (2005), Geology 33, 525-528. 5 : Harrowfield and Wilson, (2005), Journal of Structural Geology 27, 101-117. 6 : Huang et al., (2003), Journal of Metamorphic Geology 21(3), 223-240. 7 : Kirby et al., (2002), Tectonics 21(1), 10.1029/2000TC001246. 8 : Lai et al., (2007), Science in China Series D: Eath Sciences 50(2), 172-183. 9 : Mattauer et al., (1992), Comptes Rendus de l'Académie des Sciences Paris 314(6), 619-626. 10 : Nie et al., (1994), Geology 22, 999-1002. 12 : Roger et al., (1995), Earth and Planetary Science Letters 130, 201-216. 13 : Roger et al., (2004), Journal of Asian Earth Sciences 22, 465-481. 14 : Roger et al., (2008), Comptes Rendus Geoscience, Académie des sciences, Paris 340(2-3), 180-189. 15 : Wilson et al., (2006), Journal of Southeast Asian Earth Sciences 27, 341-357. 16 : Xiao et al., (2007), Lithos 96, 436-452. 17 : Xu and Kamp, (2000), Journal of Geophysical Research 105(B8), 19,231-19,251. 18 : Zhang et al., (2006), Journal of Asian Earth Sciences 27, 751-764. 19 : Zhou et al., (2008), Journal of Southeast Asian Earth Sciences 33, 414-427.

Coinage metal coordination chemistry of stable primary, secondary and tertiary ferrocenylethyl-based phosphines.

PubMed

Azizpoor Fard, M; Rabiee Kenaree, A; Boyle, P D; Ragogna, P J; Gilroy, J B; Corrigan, J F

2016-02-21

Ferrocene-based phosphines constitute an important auxiliary ligand in inorganic chemistry. Utilizing the (ferrocenylethyl)phosphines (FcCH2CH2)3-nHnP (Fc = ferrocenyl; n = 2, 1; n = 1, 2; n = 0, 3) the synthesis of a series of coordination complexes [(FcCH2CH2)3-nHnPCuCl]4 (n = 2, 1-CuCl; n = 0, 3-CuCl), [(FcCH2CH2)2HPCuCl] (2-CuCl), {[(FcCH2CH2)H2P]2AgCl}2 (1-AgCl), [(FcCH2CH2)2HPAgCl] (2-AgCl), [(FcCH2CH2)3PAgCl]4 (3-AgCl), [(FcCH2CH2)3PM(OAc)]4 (M = Cu, 3-CuOAc M = Ag, 3-AgOAc), [(FcCH2CH2)3-nHnPAuCl] (n = 1, 2-AuCl; n = 0, 3-AuCl), via the reaction between the free phosphine and MX (M = Cu, Ag and Au; X = Cl, OAc), is described. The reaction between the respective phosphine with a suspension of metal-chloride or -acetate in a 1 : 1 ratio in THF at ambient temperature affords coordinated phosphine-coinage metal complexes. Varying structural motifs are observed in the solid state, as determined via single crystal X-ray analysis of 1-CuCl, 3-CuCl, 1-AgCl, 3-AgCl, 3-CuOAc, 3-AgOAc, 2-AuCl and 3-AuCl. Complexes 1-CuCl and 3-CuCl are tetrameric Cu(i) cubane-like structures with a Cu4Cl4 core, whereas silver complexes with primary and tertiary phosphine reveal two different structural types. The structure of 1-AgCl, unlike the rest, displays the coordination of two phosphines to each silver atom and shows a quadrangle defined by two Ag and two Cl atoms. In contrast, 3-AgCl is distorted from a cubane structure via elongation of one of the ClAg distances. 3-CuOAc and 3-AgOAc are isostructural with step-like cores, while complexes 2-AuCl and 3-AuCl reveal a linear geometry of a phosphine gold(i) chloride devoid of any aurophilic interactions. All of the complexes were characterized in solution by multinuclear (1)H, (13)C{(1)H} and (31)P NMR spectroscopic techniques; the redox chemistry of the series of complexes was examined using cyclic voltammetry. This class of complexes has been found to exhibit one reversible Fe(ii)/Fe(iii) oxidation couple, suggesting the absence of electronic communication between the ferrocenyl units on individual phosphine ligands as well as between different phosphines on the polymetallic cores.

Metal stabilization of collagen and de novo designed mimetic peptides

PubMed Central

Parmar, Avanish S.; Xu, Fei; Pike, Douglas H.; Belure, Sandeep V.; Hasan, Nida F.; Drzewiecki, Kathryn E.; Shreiber, David I.; Nanda, Vikas

2017-01-01

We explore the design of metal binding sites to modulate triple-helix stability of collagen and collagen-mimetic peptides. Globular proteins commonly utilize metals to connect tertiary structural elements that are well separated in sequence, constraining structure and enhancing stability. It is more challenging to engineer structural metals into fibrous protein scaffolds, which lack the extensive tertiary contacts seen in globular proteins. In the collagen triple helix, the structural adjacency of the carboxy-termini of the three chains makes this region an attractive target for introducing metal binding sites. We engineered His3 sites based on structural modeling constraints into a series of designed homotrimeric and heterotrimeric peptides, assessing the capacity of metal binding to improve stability and in the case of heterotrimers, affect specificity of assembly. Notable enhancements in stability for both homo and heteromeric systems were observed upon addition of zinc(II) and several other metal ions only when all three histidine ligands were present. Metal binding affinities were consistent with the expected Irving-Williams series for imidazole. Unlike other metals tested, copper(II) also bound to peptides lacking histidine ligands. Acetylation of the peptide N-termini prevented copper binding, indicating proline backbone amide metal-coordination at this site. Copper similarly stabilized animal extracted Type I collagen in a metal specific fashion, highlighting the potential importance of metal homeostasis within the extracellular matrix. PMID:26225466

Covalent Bonding of Chlorogenic Acid Induces Structural Modifications on Sunflower Proteins.

PubMed

Karefyllakis, Dimitris; Salakou, Stavroula; Bitter, J Harry; van der Goot, Atze J; Nikiforidis, Constantinos V

2018-02-19

Proteins and phenols coexist in the confined space of plant cells leading to reactions between them, which result in new covalently bonded complex molecules. This kind of reactions has been widely observed during storage and processing of plant materials. However, the nature of the new complex molecules and their physicochemical properties are largely unknown. Therefore, we investigated the structural characteristics of covalently bonded complexes between sunflower protein isolate (SFPI, protein content 85 wt %) and the dominant phenol in the confined space of a sunflower seed cell (chlorogenic acid, CGA). It was shown that the efficiency of bond formation goes through a maximum as a function of the SFPI:CGA ratio. Moreover, the bonding of CGA with proteins resulted in changes in the secondary and tertiary structure of the protein. It was also shown that the phenol bound strongly to the protein, which resulted in new crosslinks between the polypeptide chains. As a result, secondary structures like α-helices and β-sheets diminished, which in turn resulted in more disordered domains and a subsequent modification of the tertiary structure of the proteins. These findings are relevant for establishing future protocols for extraction of high-quality proteins and phenols when utilizing plant material and offer insight into the impact of processing that these ingredients endure. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Solution structure of a small protein containing a fluorinated side chain in the core

PubMed Central

Cornilescu, Gabriel; Hadley, Erik B.; Woll, Matthew G.; Markley, John L.; Gellman, Samuel H.; Cornilescu, Claudia C.

2007-01-01

We report the first high-resolution structure for a protein containing a fluorinated side chain. Recently we carried out a systematic evaluation of phenylalanine to pentafluorophenylalanine (Phe → F5-Phe) mutants for the 35-residue chicken villin headpiece subdomain (c-VHP), the hydrophobic core of which features a cluster of three Phe side chains (residues 6, 10, and 17). Phe → F5-Phe mutations are interesting because aryl–perfluoroaryl interactions of optimal geometry are intrinsically more favorable than either aryl–aryl or perfluoroaryl–perfluoroaryl interactions, and because perfluoroaryl units are more hydrophobic than are analogous aryl units. Only one mutation, Phe10 → F5-Phe, was found to provide enhanced tertiary structural stability relative to the native core (by ∼1 kcal/mol, according to guanidinium chloride denaturation studies). The NMR structure of this mutant, described here, reveals very little variation in backbone conformation or side chain packing relative to the wild type. Thus, although Phe → F5-Phe mutations offer the possibility of greater tertiary structural stability from side chain–side chain attraction and/or side chain desolvation, the constraints associated with the native c-VHP fold apparently prevent the modified polypeptide from taking advantage of this possibility. Our findings are important because they complement several studies that have shown that fluorination of saturated side chain carbon atoms can provide enhanced conformational stability. PMID:17123960

Metal Stabilization of Collagen and de Novo Designed Mimetic Peptides.

PubMed

Parmar, Avanish S; Xu, Fei; Pike, Douglas H; Belure, Sandeep V; Hasan, Nida F; Drzewiecki, Kathryn E; Shreiber, David I; Nanda, Vikas

2015-08-18

We explore the design of metal binding sites to modulate triple-helix stability of collagen and collagen-mimetic peptides. Globular proteins commonly utilize metals to connect tertiary structural elements that are well separated in sequence, constraining structure and enhancing stability. It is more challenging to engineer structural metals into fibrous protein scaffolds, which lack the extensive tertiary contacts seen in globular proteins. In the collagen triple helix, the structural adjacency of the carboxy-termini of the three chains makes this region an attractive target for introducing metal binding sites. We engineered His3 sites based on structural modeling constraints into a series of designed homotrimeric and heterotrimeric peptides, assessing the capacity of metal binding to improve stability and in the case of heterotrimers, affect specificity of assembly. Notable enhancements in stability for both homo- and heteromeric systems were observed upon addition of zinc(II) and several other metal ions only when all three histidine ligands were present. Metal binding affinities were consistent with the expected Irving-Williams series for imidazole. Unlike other metals tested, copper(II) also bound to peptides lacking histidine ligands. Acetylation of the peptide N-termini prevented copper binding, indicating proline backbone amide metal-coordination at this site. Copper similarly stabilized animal extracted Type I collagen in a metal-specific fashion, highlighting the potential importance of metal homeostasis within the extracellular matrix.

Along-Strike Variation in Geometry and Kinematics of a Major, Active Intracontinental Thrust System: the Pred-Terskey Fault Zone, Kyrgyz Tien Shan, Central Asia

NASA Astrophysics Data System (ADS)

Burgette, R. J.; Weldon, R. J.; Abdrakhmatov, K. Y.; Ormukov, C.

2004-12-01

The Pred-Terskey fault zone defines the southern margin of the Issyk-Kul basin, extending eastward over 250 km from at least the Chu River to the Kazakhstan border, and appears to be one of the most active zones in the Kyrgyz Tien Shan. Despite a diversity of structural styles and changes of vergence at the surface, the lateral continuity and overall geometry of the zone is consistent with a single north vergent thrust at depth, which uplifts the Terskey Range and generally tilts the south margin of the basin to the north. This northward tilting of the margin is probably due to a flattening of the fault as it approaches the surface. In spite of historical quiescence, it is likely capable of producing great earthquakes. We have conducted detailed field mapping coupled with terrace profiling and dating at seven representative, well-exposed areas of the fault zone. Based on these field observations and satellite image and air photo interpretation along the entire zone, we identify three major divisions in structural style expressed at the surface. The western segment is typified by the Tura-Su, Ak-Terek and Ton areas. A series of left-stepping, south-vergent, basement-involved reverse faults and folds are uplifting the southern margin of the Issyk-Kul basin in this area. The resulting uphill-facing scarps have trapped and diverted many of the rivers flowing north from the Terskey Range. Tertiary strata and Quaternary geomorphic surfaces show consistent, progressive northward tilting across the entire zone. The west-central segment is represented by the Kajy-Say area. South-vergent reverse faults and a north-vergent backthrust have uplifted an arcuate granite block. Offshore of this area, the lake floor descends to a sharp break in slope with a low relief area at a depth of about 650 m. Late Quaternary geomorphic features do not show evidence of tilting. In contrast to the areas east and west, the major north-dipping thrust is likely planar over this segment and daylights at the lake floor break in slope. The east-central segment is exemplified by the Barskaun and Jety Oguz areas. A high angle reverse fault juxtaposes Paleozoic rock against Tertiary sediments. To the north, a thrust fault with a sinuous trace places north-dipping Tertiary rock over the nearly horizontal basin floor. Quaternary terraces in the hanging wall of this fault record progressive northward tilting. North of the thrust fault a series of anticlines are growing out of the basin sediments. The eastern segment, which includes the Jergalan River valley, lacks a low angle thrust fault at the basin margin. Along this segment, the basement reverse fault uplifts Paleozoic rock against Quaternary basin sediment. To the north of this range-bounding structure, late Quaternary terraces are offset by south-vergent scarps. We are calculating geologic slip rates for each of the seven sites along the Pred-Terskey zone by dating terraces and constructing structural models consistent with both the rock and terrace records. Based on preliminary radiocarbon dates, a prominent Jety Oguz River terrace is 50 +/- 10 ka. The terrace is tilted 0.5° relative to the modern river, and with the low angle fault branching off of the basement reverse fault at dips ranging between 45° and 90° , the slip rate of this fault is 6 +/- 4 mm/yr. This is consistent with the GPS shortening rate across the Pred-Terskey zone at this longitude.

An imbalance between apoptosis and proliferation contributes to follicular persistence in polycystic ovaries in rats

PubMed Central

Salvetti, Natalia R; Panzani, Carolina G; Gimeno, Eduardo J; Neme, Leandro G; Alfaro, Natalia S; Ortega, Hugo H

2009-01-01

Background Cystic ovarian disease is an important cause of infertility that affects bovine, ovine, caprine and porcine species and even human beings. Alterations in the ovarian micro-environment of females with follicular cysts could alter the normal processes of proliferation and programmed cell death in ovarian cells. Thus, our objective was to evaluate apoptosis and proliferation in ovarian cystic follicles in rats in order to investigate the cause of cystic follicle formation and persistence. Methods We compared the number of in situ apoptotic cells by TUNEL assay, expression of active caspase-3 and members of Bcl-2 family by immunohistochemistry; and cell proliferation by the expression of the proliferation markers: PCNA and Ki-67. Results The proliferation index was low in granulosa of tertiary and cystic follicles of light exposed rats when compared with tertiary follicles of control animals, while in theca interna only cystic follicles presented low proliferation index when compared with tertiary follicles (p < 0.05). The granulosa of cysts exhibited a similar cell DNA fragmentation to early atretic follicles. In the granulosa and theca interna, active caspase-3 shown similar immunostaining levels in tertiary and cystic follicles (p < 0.05). The granulosa cells presented high expression of Bcl-2, Bcl-xL and Bcl-w in the tertiary and cystic follicles with diminishing intensity in the atretic follicles, except with Bcl-w where the intensity was maintained in the atretic follicles (p < 0.05). The expression of Bax was weak in the healthy and cystic follicles. In the theca interna, Bcl-2 expression was the same as the pattern found in the granulosa; no differences were found between tertiary and cystic follicles from both groups for Bcl-xL and Bcl-w. The expression of Bax in this layer was higher in the tertiary follicles of the treated animals (p < 0.05) while the values for cystic follicles were similar to those in the tertiary follicles of controls. The theca externa showed low expression of the pro and anti-apoptotic proteins. Conclusion These results show that the combination of weak proliferation indices and low apoptosis observed in follicular cysts, could explain the cause of the slow growth of cystic follicles and the maintenance of a static condition without degeneration, which leads to their persistence. These alterations may be due to structural and functional modifications that take place in these cells and could be related to hormonal changes in animals with this condition. PMID:19570211

Tertiary carbonate-dissolution cycles on the Sierra Leone Rise, eastern equatorial Atlantic Ocean

USGS Publications Warehouse

Dean, W.E.; Gardner, J.V.; Cepek, P.

1981-01-01

Most of the Tertiary section on Sierra Leone Rise off northwest Africa consists of chalk, marl, and limestone that show cyclic alterations of clay-rich and clay-poor beds about 20-60 cm thick. On the basis of biostratigraphic accumulation rates, the cycles in Oligocene and Miocene chalk have periods which average about 44,000 years, and those in Eocene siliceous limestone have periods of 4000-27,000 years. Several sections were sampled in detail to further define the cycles in terms of content of CaCO3, clay minerals, and relative abundances of calcareous nannofossils. Extending information gained by analyses of Pleistocene cores from the continental margin of northwest Africa to the Tertiary cycles on Sierra Leone Rise, both dilution by noncarbonate material and dissolution of CaCO3 could have contributed to the observed relative variations in clay and CaCO3. However, dissolution of CaCO3 as the main cause of the carbonate-clay cycles on the Sierra Leone Rise, rather than dilution by clay, is suggested by the large amount of change (several thousand percent) in terrigenous influx required to produce the observed variations in amount of clay and by the marked increase in abundance of dissolution-resistant discoasters relative to more easily dissolved coccoliths in low-carbonate parts of cycles. The main cause of dissolution of CaCO3 was shoaling of the carbonate compensation depth (CCD) during the early Neogene and climatically induced fluctuations in the thickness of Antarctic Bottom Water. ?? 1981.

Ethiopian Tertiary dike swarms

NASA Technical Reports Server (NTRS)

Mohr, P. A.

1971-01-01

Mapping of the Ethiopian rift and Afar margins revealed the existence of Tertiary dike swarms. The structural relations of these swarms and the fed lava pile to monoclinal warping of the margins partly reflect a style of continental margin tectonics found in other parts of the world. In Ethiopia, however, conjugate dike trends appear to be unusually strongly developed. Relation of dikes to subsequent margin faulting is ambiguous, and there are instances where the two phenomena are spatially separate and of differing trends. There is no evidence for lateral migration with time of dike injection toward the rift zone. No separate impingement of Red Sea, Gulf of Aden, and African rift system stress fields on the Ethiopian region can be demonstrated from the Tertiary dike swarms. Rather, a single, regional paleostress field existed, suggestive of a focus beneath the central Ethiopian plateau. This stress field was dominated by tension: there is no cogent evidence for shearing along the rift margins. A gentle compression along the rift floor is indicated. A peculiar sympathy of dike hade directions at given localities is evident.

Petroleum Systems and Geologic Assessment of Oil and Gas Resources in the Wind River Basin Province, Wyoming

USGS Publications Warehouse

,

2007-01-01

The purpose of the U.S. Geological Survey's (USGS) National Oil and Gas Assessment is to develop geologically based hypotheses regarding the potential for additions to oil and gas reserves in priority areas of the United States. The U.S. Geological Survey (USGS) recently completed an assessment of the undiscovered oil and gas potential of the Wind River Basin Province which encompasses about 4.7 million acres in central Wyoming. The assessment is based on the geologic elements of each total petroleum system (TPS) defined in the province, including hydrocarbon source rocks (source-rock maturation, hydrocarbon generation, and migration), reservoir rocks (sequence stratigraphy and petrophysical properties), and hydrocarbon traps (trap formation and timing). Using this geologic framework, the USGS defined three TPSs: (1) Phosphoria TPS, (2) Cretaceous-Tertiary TPS, and (3) Waltman TPS. Within these systems, 12 Assessment Units (AU) were defined and undiscovered oil and gas resources were quantitatively estimated within 10 of the 12 AUs.

The Talara Basin province of northwestern Peru: cretaceous-tertiary total petroleum system

USGS Publications Warehouse

Higley, Debra K.

2004-01-01

More than 1.68 billion barrels of oil (BBO) and 340 billion cubic feet of gas (BCFG) have been produced from the Cretaceous-Tertiary Total Petroleum System in the Talara Basin province, northwestern Peru. Oil and minor gas fields are concentrated in the onshore northern third of the province. Current production is primarily oil, but there is excellent potential for offshore gas resources, which is a mostly untapped resource because of the limited local market for gas and because there are few pipelines. Estimated mean recoverable resources from undiscovered fields in the basin are 1.71 billion barrels of oil (BBO), 4.79 trillion cubic feet of gas (TCFG), and 255 million barrels of natural gas liquids (NGL). Of this total resource, 15 percent has been allocated to onshore and 85 percent to offshore; volumes are 0.26 BBO and 0.72 TCFG onshore, and 1.45 BBO and 4.08 TCFG offshore. The mean estimate of numbers of undiscovered oil and gas fields is 83 and 27, respectively. Minimum size of fields that were used in this analysis is 1 million barrels of oil equivalent and (or) 6 BCFG. The Paleocene Talara forearc basin is superimposed on a larger, Mesozoic and pre-Mesozoic basin. Producing formations, ranging in age from Pennsylvanian to Oligocene, are mainly Upper Cretaceous through Oligocene sandstones of fluvial, deltaic, and nearshore to deep-marine depositional origins. The primary reservoirs and greatest potential for future development are Eocene sandstones that include turbidites of the Talara and Salinas Groups. Additional production and undiscovered resources exist within Upper Cretaceous, Paleocene, and Oligocene formations. Pennsylvanian Amotape quartzites may be productive where fractured. Trap types in this block-faulted basin are mainly structural or a combination of structure and stratigraphy. Primary reservoir seals are interbedded and overlying marine shales. Most fields produce from multiple reservoirs, and production is reported commingled. For this reason, and also because geochemical data on oils and source rocks is very limited, Tertiary and Cretaceous production is grouped into one total petroleum system. The most likely source rocks are Tertiary marine shales, but some of the Cretaceous marine shales are also probable source rocks, and these would represent separate total petroleum systems. Geochemical data on one oil sample from Pennsylvanian rock indicates that it was probably also sourced from Tertiary shales.

Forgotten, excluded or included? Students with disabilities: A case study at the University of Mauritius.

PubMed

Pudaruth, Sameerchand; Gunputh, Rajendra P; Singh, Upasana G

2017-01-01

Students with disabilities in the tertiary education sector are more than a just a phenomenon, they are a reality. In general, little attention is devoted to their needs despite the fact that they need more care and attention. This paper, through a case study at the University of Mauritius, sought to answer some pertinent questions regarding students with disabilities. Does the University of Mauritius have sufficient facilities to support these students? Are students aware of existing facilities? What additional structures need to be put in place so that students with any form of disability are neither victimised, nor their education undermined? Are there any local laws about students with disabilities in higher education? To answer these questions and others, an online questionnaire was sent to 500 students and the responses were then analysed and discussed. The response rate was 24.4% which showed that students were not reticent to participate in this study. Our survey revealed that most students were not aware of existing facilities and were often neglected in terms of supporting structures and resources. ICT facilities were found to be the best support that is provided at the University of Mauritius. The right legal framework for tertiary education was also missing. Ideally, students with disabilities should have access to special facilities to facilitate their learning experiences at tertiary institutions. Awareness about existing facilities must also be raised in order to offer equal opportunities to them and to enable a seamless inclusion.

Tertiary to secondary reduction of aminomethylphosphane derived from 1-ethylpiperazine as a result of its coordination to ruthenium(II) centre - The first insight into the nature of process

NASA Astrophysics Data System (ADS)

Płotek, Michał; Starosta, Radosław; Komarnicka, Urszula K.; Skórska-Stania, Agnieszka; Kołoczek, Przemysław; Dudek, Karol; Kyzioł, Agnieszka

2016-10-01

Introduction of tertiary aminomethylphosphane P{CH2N(CH2CH2)2NCH2CH3}3 (B; tris{1-[4-ethyl(tetrahydro-1,4-diazino)]methyl}phosphane) to methanolic solution of [Ru(η5-C5H5)Cl(PPh3)2] (1) and NaBF4, instead of straightforward substitution of the chloride leads to concomitant cleavage of aminomethylphosphane's Psbnd CH2 bond. The obtained complex [Ru(η5-C5H5)PH{CH2N(CH2CH2)2NCH2CH3}2(PPh3)2]BF4 (2B‧) was fully characterized by spectroscopic methods ((NMR, IR, ESI-MS) and its solid state structure was determined with single crystal X-ray diffraction method. It was proven that the structure of 2B‧ is similar to the previously synthesized morpholine counterpart [Ru(η5-C5H5)PH{CH2N(CH2CH2)2O}2(PPh3)2]BF4 (2A‧). DFT calculations (B3LYP with the D95V(d,p) basis set for C, N, H and O and LanL2DZ with Los Alamos ECPs for Ru, P and Cl) revealed that the binding of aminomethylphosphanes to the ruthenium centre leads to the Psbnd C bonds elongation, which may finally result in breaking one of them and phosphane's reduction from tertiary to secondary ones.

Biotransformation of Two Pharmaceuticals by the Ammonia-Oxidizing Archaeon Nitrososphaera gargensis

PubMed Central

2016-01-01

The biotransformation of some micropollutants has previously been observed to be positively associated with ammonia oxidation activities and the transcript abundance of the archaeal ammonia monooxygenase gene (amoA) in nitrifying activated sludge. Given the increasing interest in and potential importance of ammonia-oxidizing archaea (AOA), we investigated the capabilities of an AOA pure culture, Nitrososphaera gargensis, to biotransform ten micropollutants belonging to three structurally similar groups (i.e., phenylureas, tertiary amides, and tertiary amines). N. gargensis was able to biotransform two of the tertiary amines, mianserin (MIA) and ranitidine (RAN), exhibiting similar compound specificity as two ammonia-oxidizing bacteria (AOB) strains that were tested for comparison. The same MIA and RAN biotransformation reactions were carried out by both the AOA and AOB strains. The major transformation product (TP) of MIA, α-oxo MIA was likely formed via a two-step oxidation reaction. The first hydroxylation step is typically catalyzed by monooxygenases. Three RAN TP candidates were identified from nontarget analysis. Their tentative structures and possible biotransformation pathways were proposed. The biotransformation of MIA and RAN only occurred when ammonia oxidation was active, suggesting cometabolic transformations. Consistently, a comparative proteomic analysis revealed no significant differential expression of any protein-encoding gene in N. gargensis grown on ammonium with MIA or RAN compared with standard cultivation on ammonium only. Taken together, this study provides first important insights regarding the roles played by AOA in micropollutant biotransformation. PMID:27046099

Three-dimensional hydrogeologic framework model for use with a steady-state numerical ground-water flow model of the Death Valley regional flow system, Nevada and California

USGS Publications Warehouse

Belcher, Wayne R.; Faunt, Claudia C.; D'Agnese, Frank A.

2002-01-01

The U.S. Geological Survey, in cooperation with the Department of Energy and other Federal, State, and local agencies, is evaluating the hydrogeologic characteristics of the Death Valley regional ground-water flow system. The ground-water flow system covers an area of about 100,000 square kilometers from latitude 35? to 38?15' North to longitude 115? to 118? West, with the flow system proper comprising about 45,000 square kilometers. The Death Valley regional ground-water flow system is one of the larger flow systems within the Southwestern United States and includes in its boundaries the Nevada Test Site, Yucca Mountain, and much of Death Valley. Part of this study includes the construction of a three-dimensional hydrogeologic framework model to serve as the foundation for the development of a steady-state regional ground-water flow model. The digital framework model provides a computer-based description of the geometry and composition of the hydrogeologic units that control regional flow. The framework model of the region was constructed by merging two previous framework models constructed for the Yucca Mountain Project and the Environmental Restoration Program Underground Test Area studies at the Nevada Test Site. The hydrologic characteristics of the region result from a currently arid climate and complex geology. Interbasinal regional ground-water flow occurs through a thick carbonate-rock sequence of Paleozoic age, a locally thick volcanic-rock sequence of Tertiary age, and basin-fill alluvium of Tertiary and Quaternary age. Throughout the system, deep and shallow ground-water flow may be controlled by extensive and pervasive regional and local faults and fractures. The framework model was constructed using data from several sources to define the geometry of the regional hydrogeologic units. These data sources include (1) a 1:250,000-scale hydrogeologic-map compilation of the region; (2) regional-scale geologic cross sections; (3) borehole information, and (4) gridded surfaces from a previous three-dimensional geologic model. In addition, digital elevation model data were used in conjunction with these data to define ground-surface altitudes. These data, properly oriented in three dimensions by using geographic information systems, were combined and gridded to produce the upper surfaces of the hydrogeologic units used in the flow model. The final geometry of the framework model is constructed as a volumetric model by incorporating the intersections of these gridded surfaces and by applying fault truncation rules to structural features from the geologic map and cross sections. The cells defining the geometry of the hydrogeologic framework model can be assigned several attributes such as lithology, hydrogeologic unit, thickness, and top and bottom altitudes.

Impact of the structural integrity of the three-way junction of adenovirus VAI RNA on PKR inhibition

PubMed Central

Dzananovic, Edis; Astha; Chojnowski, Grzegorz; Deo, Soumya; Booy, Evan P.; Padilla-Meier, Pauline; McEleney, Kevin; Bujnicki, Janusz M.; McKenna, Sean A.

2017-01-01

Highly structured RNA derived from viral genomes is a key cellular indicator of viral infection. In response, cells produce the interferon inducible RNA-dependent protein kinase (PKR) that, when bound to viral dsRNA, phosphorylates eukaryotic initiation factor 2α and attenuates viral protein translation. Adenovirus can evade this line of defence through transcription of a non-coding RNA, VAI, an inhibitor of PKR. VAI consists of three base-paired regions that meet at a three-way junction; an apical stem responsible for the interaction with PKR, a central stem required for inhibition, and a terminal stem. Recent studies have highlighted the potential importance of the tertiary structure of the three-way junction to PKR inhibition by enabling interaction between regions of the central and terminal stems. To further investigate the role of the three-way junction, we characterized the binding affinity and inhibitory potential of central stem mutants designed to introduce subtle alterations. These results were then correlated with small-angle X-ray scattering solution studies and computational tertiary structural models. Our results demonstrate that while mutations to the central stem have no observable effect on binding affinity to PKR, mutations that appear to disrupt the structure of the three-way junction prevent inhibition of PKR. Therefore, we propose that instead of simply sequestering PKR, a specific structural conformation of the PKR-VAI complex may be required for inhibition. PMID:29053745

Tertiary model of a plant cellulose synthase

PubMed Central

Sethaphong, Latsavongsakda; Haigler, Candace H.; Kubicki, James D.; Zimmer, Jochen; Bonetta, Dario; DeBolt, Seth; Yingling, Yaroslava G.

2013-01-01

A 3D atomistic model of a plant cellulose synthase (CESA) has remained elusive despite over forty years of experimental effort. Here, we report a computationally predicted 3D structure of 506 amino acids of cotton CESA within the cytosolic region. Comparison of the predicted plant CESA structure with the solved structure of a bacterial cellulose-synthesizing protein validates the overall fold of the modeled glycosyltransferase (GT) domain. The coaligned plant and bacterial GT domains share a six-stranded β-sheet, five α-helices, and conserved motifs similar to those required for catalysis in other GT-2 glycosyltransferases. Extending beyond the cross-kingdom similarities related to cellulose polymerization, the predicted structure of cotton CESA reveals that plant-specific modules (plant-conserved region and class-specific region) fold into distinct subdomains on the periphery of the catalytic region. Computational results support the importance of the plant-conserved region and/or class-specific region in CESA oligomerization to form the multimeric cellulose–synthesis complexes that are characteristic of plants. Relatively high sequence conservation between plant CESAs allowed mapping of known mutations and two previously undescribed mutations that perturb cellulose synthesis in Arabidopsis thaliana to their analogous positions in the modeled structure. Most of these mutation sites are near the predicted catalytic region, and the confluence of other mutation sites supports the existence of previously undefined functional nodes within the catalytic core of CESA. Overall, the predicted tertiary structure provides a platform for the biochemical engineering of plant CESAs. PMID:23592721

Massive integration of diverse protein quality assessment methods to improve template based modeling in CASP11

PubMed Central

Cao, Renzhi; Bhattacharya, Debswapna; Adhikari, Badri; Li, Jilong; Cheng, Jianlin

2015-01-01

Model evaluation and selection is an important step and a big challenge in template-based protein structure prediction. Individual model quality assessment methods designed for recognizing some specific properties of protein structures often fail to consistently select good models from a model pool because of their limitations. Therefore, combining multiple complimentary quality assessment methods is useful for improving model ranking and consequently tertiary structure prediction. Here, we report the performance and analysis of our human tertiary structure predictor (MULTICOM) based on the massive integration of 14 diverse complementary quality assessment methods that was successfully benchmarked in the 11th Critical Assessment of Techniques of Protein Structure prediction (CASP11). The predictions of MULTICOM for 39 template-based domains were rigorously assessed by six scoring metrics covering global topology of Cα trace, local all-atom fitness, side chain quality, and physical reasonableness of the model. The results show that the massive integration of complementary, diverse single-model and multi-model quality assessment methods can effectively leverage the strength of single-model methods in distinguishing quality variation among similar good models and the advantage of multi-model quality assessment methods of identifying reasonable average-quality models. The overall excellent performance of the MULTICOM predictor demonstrates that integrating a large number of model quality assessment methods in conjunction with model clustering is a useful approach to improve the accuracy, diversity, and consequently robustness of template-based protein structure prediction. PMID:26369671

Recovery of bioactive protein from bacterial inclusion bodies using trifluoroethanol as solubilization agent.

PubMed

Upadhyay, Vaibhav; Singh, Anupam; Jha, Divya; Singh, Akansha; Panda, Amulya K

2016-06-08

Formation of inclusion bodies poses a major hurdle in recovery of bioactive recombinant protein from Escherichia coli. Urea and guanidine hydrochloride have routinely been used to solubilize inclusion body proteins, but many times result in poor recovery of bioactive protein. High pH buffers, detergents and organic solvents like n-propanol have been successfully used as mild solubilization agents for high throughput recovery of bioactive protein from bacterial inclusion bodies. These mild solubilization agents preserve native-like secondary structures of proteins in inclusion body aggregates and result in improved recovery of bioactive protein as compared to conventional solubilization agents. Here we demonstrate solubilization of human growth hormone inclusion body aggregates using 30% trifluoroethanol in presence of 3 M urea and its refolding into bioactive form. Human growth hormone was expressed in E. coli M15 (pREP) cells in the form of inclusion bodies. Different concentrations of trifluoroethanol with or without addition of low concentration (3 M) of urea were used for solubilization of inclusion body aggregates. Thirty percent trifluoroethanol in combination with 3 M urea was found to be suitable for efficient solubilization of human growth hormone inclusion bodies. Solubilized protein was refolded by dilution and purified by anion exchange and size exclusion chromatography. Purified protein was analyzed for secondary and tertiary structure using different spectroscopic tools and was found to be bioactive by cell proliferation assay. To understand the mechanism of action of trifluoroethanol, secondary and tertiary structure of human growth hormone in trifluoroethanol was compared to that in presence of other denaturants like urea and guanidine hydrochloride. Trifluoroethanol was found to be stabilizing the secondary structure and destabilizing the tertiary structure of protein. Finally, it was observed that trifluoroethanol can be used to solubilize inclusion bodies of a number of proteins. Trifluoroethanol was found to be a suitable mild solubilization agent for bacterial inclusion bodies. Fully functional, bioactive human growth hormone was recovered in high yield from inclusion bodies using trifluoroethanol based solubilization buffer. It was also observed that trifluoroethanol has potential to solubilize inclusion bodies of different proteins.

Correlation of RNA secondary structure statistics with thermodynamic stability and applications to folding.

PubMed

Wu, Johnny C; Gardner, David P; Ozer, Stuart; Gutell, Robin R; Ren, Pengyu

2009-08-28

The accurate prediction of the secondary and tertiary structure of an RNA with different folding algorithms is dependent on several factors, including the energy functions. However, an RNA higher-order structure cannot be predicted accurately from its sequence based on a limited set of energy parameters. The inter- and intramolecular forces between this RNA and other small molecules and macromolecules, in addition to other factors in the cell such as pH, ionic strength, and temperature, influence the complex dynamics associated with transition of a single stranded RNA to its secondary and tertiary structure. Since all of the factors that affect the formation of an RNAs 3D structure cannot be determined experimentally, statistically derived potential energy has been used in the prediction of protein structure. In the current work, we evaluate the statistical free energy of various secondary structure motifs, including base-pair stacks, hairpin loops, and internal loops, using their statistical frequency obtained from the comparative analysis of more than 50,000 RNA sequences stored in the RNA Comparative Analysis Database (rCAD) at the Comparative RNA Web (CRW) Site. Statistical energy was computed from the structural statistics for several datasets. While the statistical energy for a base-pair stack correlates with experimentally derived free energy values, suggesting a Boltzmann-like distribution, variation is observed between different molecules and their location on the phylogenetic tree of life. Our statistical energy values calculated for several structural elements were utilized in the Mfold RNA-folding algorithm. The combined statistical energy values for base-pair stacks, hairpins and internal loop flanks result in a significant improvement in the accuracy of secondary structure prediction; the hairpin flanks contribute the most.

New functions of an old protein: the eukaryotic porin or voltage dependent anion selective channel (VDAC).

PubMed

De Pinto, Vito; Messina, Angela; Accardi, Rosita; Aiello, Rita; Guarino, Francesca; Tomasello, Marianna Flora; Tommasino, Massimo; Tasco, Gianluca; Casadio, Rita; Benz, Roland; De Giorgi, Francesca; Ichas, François; Baker, Mark; Lawen, Alfons

2003-03-01

Mitochondrial porin or VDAC (Voltage Dependent Anion selective Channels) was identified for the first time in 1976, on the basis of the evolutionary similarity between the gram negative and mitochondrial outer membranes. Since this achievement VDAC has been extensively investigated: its functional features have been sharply defined upon reconstitution in artificial membranes and its sequence has been determined in many genomes. Unfortunately the tertiary structure has not yet been solved, mainly because it proved to be very difficult to get suitable crystals. Despite this established knowledge, in the last few years this protein has attracted renewed interest. There are two main reasons for this interest: the discovery, in most eukaryotes, of a family of genes encoding VDAC isoforms and the claims of VDAC involvement in the intrinsic pathway of apoptosis and in particular in the mechanism of cytochrome c release from mitochondria. We can affirm that nowadays the eukaryotic porin (or VDAC) is studied in a more general cellular contest, looking at the interactions and integration with other molecules, since VDAC is in a crucial position in the cell, forming the main interface between the mitochondrial and the cellular metabolisms. In this minireview we will briefly focus our attention onto the following topics: 1) recent advances about the structure of VDAC; 2) the VDAC-related multigene families; 3) the presence, targeting and function of VDAC in various cell membranes.

Statistical Process Control: A Quality Tool for a Venous Thromboembolic Disease Registry.

PubMed

Posadas-Martinez, Maria Lourdes; Rojas, Liliana Paloma; Vazquez, Fernando Javier; De Quiros, Fernan Bernaldo; Waisman, Gabriel Dario; Giunta, Diego Hernan

2016-01-01

We aim to describe Statistical Control Process as a quality tool for the Institutional Registry of Venous Thromboembolic Disease (IRTD), a registry developed in a community-care tertiary hospital in Buenos Aires, Argentina. The IRTD is a prospective cohort. The process of data acquisition began with the creation of a computerized alert generated whenever physicians requested imaging or laboratory study to diagnose venous thromboembolism, which defined eligible patients. The process then followed a structured methodology for patient's inclusion, evaluation, and posterior data entry. To control this process, process performance indicators were designed to be measured monthly. These included the number of eligible patients, the number of included patients, median time to patient's evaluation, and percentage of patients lost to evaluation. Control charts were graphed for each indicator. The registry was evaluated in 93 months, where 25,757 patients were reported and 6,798 patients met inclusion criteria. The median time to evaluation was 20 hours (SD, 12) and 7.7% of the total was lost to evaluation. Each indicator presented trends over time, caused by structural changes and improvement cycles, and therefore the central limit suffered inflexions. Statistical process control through process performance indicators allowed us to control the performance of the registry over time to detect systematic problems. We postulate that this approach could be reproduced for other clinical registries.

Global discourses and experiential speculation: Secondary and tertiary graduate Malawians dissect the HIV/AIDS epidemic

PubMed Central

2011-01-01

Background Since the beginning of the HIV/AIDS epidemic, the perspectives of secondary and tertiary school graduates in sub-Saharan Africa regarding the effectiveness of government and international HIV/AIDS policies and programmes have not been thoroughly examined. When extensive monetary aid is directed toward "development" in a country like Malawi, it is the educated elites - secondary and tertiary graduates who are heavily involved and influential in the domestic re-distribution and implementation of millions of dollars worth of aid - on whom international expectations fall to decrease the transmission of HIV. Many Malawian jobs related to public health and HIV/AIDS are created as a direct result of this funding and are occupied by the few secondary and tertiary graduates. Thus, it is a practical venture to understand their perspectives on highly contentious and heavily funded HIV/AIDS issues that affect their nation. Methods Qualitative data was collected in this study in efforts to discover in-depth perspectives on the HIV/AIDS epidemic. Thirty-eight secondary and tertiary graduate Malawians took part in semi-structured interviews. Data was analysed using an early grounded theory approach and subsequent themes of "global discourses" and "experiential knowledge of HIV/AIDS" emerged. Results This group of Malawians frequently responded to questions regarding healthcare and access to medicine, sexual behaviours and methods of reducing the spread of HIV/AIDS by citing and explaining the widespread, international and "proper" responses. The secondary and tertiary graduate Malawians also discussed these same topics in terms of what they perceive or have experienced. Experiential responses, such as the counter-productivity of circumcision and condoms, the overestimation of HIV/AIDS prevalence, and calls for more authoritarian policing of commercial sex work, were remarkably divergent from the HIV/AIDS discourse. Conclusions The opinions of this group of secondary and tertiary graduate Malawians do not always coincide with the current literature and policies. They give deeper insight into what is perceived and what may be taking place, and hint at what the future holds for their people. The widespread and divergent perspectives must be seriously considered because these experiences describe the potential positive and negative consequences that occur on the ground throughout Malawi as a result of HIV/AIDS policies. PMID:21970719

Global discourses and experiential speculation: Secondary and tertiary graduate Malawians dissect the HIV/AIDS epidemic.

PubMed

Myroniuk, Tyler W

2011-10-04

Since the beginning of the HIV/AIDS epidemic, the perspectives of secondary and tertiary school graduates in sub-Saharan Africa regarding the effectiveness of government and international HIV/AIDS policies and programmes have not been thoroughly examined. When extensive monetary aid is directed toward "development" in a country like Malawi, it is the educated elites - secondary and tertiary graduates who are heavily involved and influential in the domestic re-distribution and implementation of millions of dollars worth of aid - on whom international expectations fall to decrease the transmission of HIV. Many Malawian jobs related to public health and HIV/AIDS are created as a direct result of this funding and are occupied by the few secondary and tertiary graduates. Thus, it is a practical venture to understand their perspectives on highly contentious and heavily funded HIV/AIDS issues that affect their nation. Qualitative data was collected in this study in efforts to discover in-depth perspectives on the HIV/AIDS epidemic. Thirty-eight secondary and tertiary graduate Malawians took part in semi-structured interviews. Data was analysed using an early grounded theory approach and subsequent themes of "global discourses" and "experiential knowledge of HIV/AIDS" emerged. This group of Malawians frequently responded to questions regarding healthcare and access to medicine, sexual behaviours and methods of reducing the spread of HIV/AIDS by citing and explaining the widespread, international and "proper" responses. The secondary and tertiary graduate Malawians also discussed these same topics in terms of what they perceive or have experienced. Experiential responses, such as the counter-productivity of circumcision and condoms, the overestimation of HIV/AIDS prevalence, and calls for more authoritarian policing of commercial sex work, were remarkably divergent from the HIV/AIDS discourse. The opinions of this group of secondary and tertiary graduate Malawians do not always coincide with the current literature and policies. They give deeper insight into what is perceived and what may be taking place, and hint at what the future holds for their people. The widespread and divergent perspectives must be seriously considered because these experiences describe the potential positive and negative consequences that occur on the ground throughout Malawi as a result of HIV/AIDS policies.

Experiences of visually impaired students in higher education: Bodily perspectives on inclusive education.

PubMed

Lourens, Heidi; Swartz, Leslie

Although previous literature sheds light on the experiences of visually impaired students on tertiary grounds, these studies failed to provide an embodied understanding of their lives. In-depth interviews with 15 visually impaired students at one university demonstrated the ways in which they experienced their disability and the built environment in their bodies. At the same time, lost, fearful, shameful and aching bodies revealed prevailing gaps in provision for disabled students. Through this research it becomes clear how the environment is acutely felt within fleshly worlds, while bodies do not fail to tell of disabling societal structures. Based on the bodily stories, we thus make recommendations to improve the lives of visually impaired students on tertiary campuses.

Extent and character of early tertiary penetrative deformation, Sonora, Northwest Mexico

NASA Technical Reports Server (NTRS)

Anderson, T. H.

1985-01-01

Reconnaissance field work has led to the recognition of extensive Early Tertiary gneiss and schist which are distinguished by weakly developed to highly conspicous northeast to east-trending stretching lineation commonly accompanied by low-dipping foliation. This structural fabric has been imposed on Precambrian to Paleogene rocks. Regionally, minimum ages of deformation are based upon interpreted U-Pb isotopic ages from suites of cogenetic zircon from the Paleogene orthogneiss. Locally, the interpreted ages indicate that ductile deformation continued as late as Oligocene (Anderson and others, 1980; Silver and Anderson, 1984). The consistency of the deformational style is such that, although considerable variation in intensity exists, the fabric can be recognized and correlated in rocks away from the Paleogene orthogneiss.

Hydrogeology, groundwater levels, and generalized potentiometric-surface map of the Green River Basin lower Tertiary aquifer system, 2010–14, in the northern Green River structural basin

USGS Publications Warehouse

Bartos, Timothy T.; Hallberg, Laura L.; Eddy-Miller, Cheryl

2015-07-14

The groundwater-level measurements were used to construct a generalized potentiometric-surface map of the Green River Basin lower Tertiary aquifer system. Groundwater-level altitudes measured in nonflowing and flowing wells used to construct the potentiometric-surface map ranged from 6,451 to 7,307 feet (excluding four unmeasured flowing wells used for contour construction purposes). The potentiometric-surface map indicates that groundwater in the study area generally moves from north to south, but this pattern of flow is altered locally by groundwater divides, groundwater discharge to the Green River, and possibly to a tributary river (Big Sandy River) and two reservoirs (Fontenelle and Big Sandy Reservoirs).

Experiences of visually impaired students in higher education: Bodily perspectives on inclusive education

PubMed Central

Lourens, Heidi; Swartz, Leslie

2016-01-01

Although previous literature sheds light on the experiences of visually impaired students on tertiary grounds, these studies failed to provide an embodied understanding of their lives. In-depth interviews with 15 visually impaired students at one university demonstrated the ways in which they experienced their disability and the built environment in their bodies. At the same time, lost, fearful, shameful and aching bodies revealed prevailing gaps in provision for disabled students. Through this research it becomes clear how the environment is acutely felt within fleshly worlds, while bodies do not fail to tell of disabling societal structures. Based on the bodily stories, we thus make recommendations to improve the lives of visually impaired students on tertiary campuses. PMID:27917028

Lead isotope compositions of Late Cretaceous and early Tertiary igneous rocks and sulfide minerals in Arizona: Implications for the sources of plutons and metals in porphyry copper deposits

USGS Publications Warehouse

Bouse, R.M.; Ruiz, J.; Titley, S.R.; Tosdal, R.M.; Wooden, J.L.

1999-01-01

Porphyry copper deposits in Arizona are genetically associated with Late Cretaceous and early Tertiary igneous complexes that consist of older intermediate volcanic rocks and younger intermediate to felsic intrusions. The igneous complexes and their associated porphyry copper deposits were emplaced into an Early Proterozoic basement characterized by different rocks, geologic histories, and isotopic compositions. Lead isotope compositions of the Proterozoic basement rocks define, from northwest to southeast, the Mojave, central Arizona, and southeastern Arizona provinces. Porphyry copper deposits are present in each Pb isotope province. Lead isotope compositions of Late Cretaceous and early Tertiary plutons, together with those of sulfide minerals in porphyry copper deposits and of Proterozoic country rocks, place important constraints on genesis of the magmatic suites and the porphyry copper deposits themselves. The range of age-corrected Pb isotope compositions of plutons in 12 Late Cretaceous and early Tertiary igneous complexes is 206Pb/204Pb = 17.34 to 22.66, 207Pb/204Pb = 15.43 to 15.96, and 208Pb/204Pb = 37.19 to 40.33. These Pb isotope compositions and calculated model Th/U are similar to those of the Proterozoic rocks in which the plutons were emplaced, thereby indicating that Pb in the younger rocks and ore deposits was inherited from the basement rocks and their sources. No Pb isotope differences distinguish Late Cretaceous and early Tertiary igneous complexes that contain large economic porphyry copper deposits from less rich or smaller deposits that have not been considered economic for mining. Lead isotope compositions of Late Cretaceous and early Tertiary plutons and sulfide minerals from 30 metallic mineral districts, furthermore, require that the southeastern Arizona Pb province be divided into two subprovinces. The northern subprovince has generally lower 206Pb/204Pb and higher model Th/U, and the southern subprovince has higher 206Pb/204Pb and lower model Th/U. These Pb isotope differences are inferred to result from differences in their respective post-1.7 Ga magmatic histories. Throughout Arizona, Pb isotope compositions of Late Cretaceous and early Tertiary plutons and associated sulfide minerals are distinct from those of Jurassic plutons and also middle Tertiary igneous rocks and sulfide minerals. These differences most likely reflect changes in tectonic setting and magmatic sources. Within Late Cretaceous and early Tertiary igneous complexes that host economic porphyry copper deposits, there is commonly a decrease in Pb isotope composition from older to younger plutons. This decrease in Pb isotope values with time suggests an increasing involvement of crust with lower U/Pb than average crust in the source(s) of Late Cretaceous and early Tertiary magmas. Lead isotope compositions of the youngest porphyries in the igneous complexes are similar to those in most sulfide minerals within the associated porphyry copper deposit. This Pb isotope similarity argues for a genetic link between them. However, not all Pb in the sulfide minerals in porphyry copper deposits is magmatically derived. Some sulfide minerals, particularly those that are late stage, or distal to the main orebody, or in Proterozoic or Paleozoic rocks, have elevated Pb isotope compositions displaced toward the gross average Pb isotope composition of the local country rocks. The more radiogenic isotopic compositions argue for a contribution of Pb from those rocks at the site of ore deposition. Combining the Pb isotope data with available geochemical, isotopic, and petrologic data suggests derivation of the young porphyry copper-related plutons, most of their Pb, and other metals from a hybridized lower continental crustal source. Because of the likely involvement of subduction-related mantle-derived basaltic magma in the hybridized lower crustal source, an indiscernible mantle contribution is probable in the porphyry magmas. Clearly, in addition

Ground Truth, Magnitude Calibration, and Regional Phase Propagation and Detection in the Middle East and the Horn of Africa

DTIC Science & Technology

2008-09-01

Arabian Shield. Background The Arabian Shield consists of a late Proterozoic crystalline basement overlain by Tertiary and Quaternary volcanic...mantle structure under the Arabian Shield using body waves, we measured and inverted relative travel times from stations in Arabia. We augmented the...Rodgers, and A. Al-Amri (2008). S wave velocity structure of the Arabian Shield upper mantle from Rayleigh wave tomography, Geochem. Geophys

European Science Notes, Volume 40, Number 7.

DTIC Science & Technology

1986-07-01

for example, University of i.e., the details of protein-protein, Gbttingen--have departments of biochem- protein-nucleic acid , and nucleic acid ...istry but do not award degrees in bio- nucleic acid interactions and their reg- chemistry.) The Institute for Biochem- ulation is still to be resolved. A...tertiary structure acids structure and function; protein/ of the 5S rRNA molecule--the folding of nucleic- acid interactions; molecular the entire molecule of

Polyphase tertiary fold-and-thrust tectonics in the Belluno Dolomites: new mapping, kinematic analysis, and 3D modelling

NASA Astrophysics Data System (ADS)

Chistolini, Filippo; Bistacchi, Andrea; Massironi, Matteo; Consonni, Davide; Cortinovis, Silvia

2014-05-01

The Belluno Dolomites are comprised in the eastern sector of the Southern Alps, which corresponds to the fold-and-thrust belt at the retro-wedge of the Alpine collisional orogen. They are characterized by a complex and polyphase fold-and-thrust tectonics, highlighted by multiple thrust sheets and thrust-related folding. We have studied this tectonics in the Vajont area where a sequence of Jurassic, Cretaceous and Tertiary units have been involved in multiple deformations. The onset of contractional tectonics in this part of the Alps is constrained to be Tertiary (likely Post-Eocene) by structural relationships with the Erto Flysch, whilst in the Mesozoic tectonics was extensional. We have recognized two contractional deformation phases (D1 and D2 in the following), of which only the second was mentioned in previous studies of the area and attributed to the Miocene Neoalpine event. D1 and D2 are characterized by roughly top-to-WSW (possibly Dinaric) and top-to-S (Alpine) transport directions respectively, implying a 90° rotation of the regional-scale shortening axis, and resulting in complex thrust and fold interference and reactivation patterns. Geological mapping and detailed outcrop-scale kinematic analysis allowed us to characterize the kinematics and chronology of deformations. Particularly, relative chronology was unravelled thanks to (1) diagnostic fold interference patterns and (2) crosscutting relationships between thrust faults and thrust-related folds. A km-scale D1 syncline, filled with the Eocene Erto Flysch and "decapitated" by a D2 thrust fault, provides the best map-scale example of crosscutting relationships allowing to reconstruct the faulting history. Due to the strong competence contrast between Jurassic carbonates and Tertiary flysch, in this syncline spectacular duplexes were also developed during D2. In order to quantitatively characterize the complex interference pattern resulting from two orthogonal thrusting and folding events, we performed a dip-domain analysis that allowed to categorize the different fold limbs and reduce the uncertainty in the reconstruction of the fault network topology in map view. This enabled us to reconstruct a high-quality, low-uncertainty 3D structural and geological model, which unambiguously proves that deformations with a top-to-WSW Dinaric transport direction propagate farther to the west than previously supposed in this part of the Southern Alps. Our new structural reconstruction of the Vajont valley have also clarified the structural control on the 1963 catastrophic landslide (which caused over 2000 losses). Besides being a challenging natural laboratory for testing analysis and modelling methodologies to be used when reconstructing in 3D this kind of complex interference structures, the Vajont area also provides useful clues on the still-enigmatic structures in the frontal part of the Friuli-Venetian Southern Alps, buried in the Venetian Plain foredeep. These include active seismogenic thrust-faults and, at the same time, represent a growing interest for the oil industry.

Higher Education in Europe. Higher Education Policy Series 16.

ERIC Educational Resources Information Center

Gellert, Claudius, Ed.

This book addresses some of the major institutional and structural changes that have occurred in European universities and other tertiary institutions in recent years. It includes descriptive accounts of new developments in organizational patterns and discusses how new demands from the labor market and changing sociopolitical expectations have…

Quality Assurance in Sub-Saharan Africa

ERIC Educational Resources Information Center

Materu, Peter; Righetti, Petra

2010-01-01

This article assesses the status and practice of higher education quality assurance in sub-Saharan Africa, focusing on degree-granting tertiary institutions. A main finding is that structured national-level quality assurance processes in African higher education are a very recent phenomenon and that most countries face major capacity constraints.…

Designing Journalism Capstone Units That Demonstrate Student Skills

ERIC Educational Resources Information Center

Cullen, Trevor

2016-01-01

There are considerable differences in the structure, content, and delivery of tertiary journalism degrees in Australia as identified in a 2014 Office for Learning and Teaching (OLT) Innovation and Development Project report on graduate qualities and journalism curriculum renewal. To address this situation, the author argues for journalism capstone…

Crediting Vocational Education and Training for Learner Mobility

ERIC Educational Resources Information Center

Walls, Sandra; Pardy, John

2010-01-01

Reforms in the tertiary education sector place student transitions between vocational education and training (VET) and university at the fore. Informed by existing structures between Deakin University and three Victorian technical and further education (TAFE) institutes, this project explores the notion of credit transfer in practice, as well as…

Colleges and the Governance of Higher Education

ERIC Educational Resources Information Center

Parry, Gareth

2013-01-01

The governance of higher education in colleges and college sectors that offer other types of education and training is distinctive in four main respects. First, governance structures are frequently separate and different for higher education and for other segments of tertiary education. Second, the size and scope of the higher-level education…

Social Ecology as Innovative Tertiary Environmental Education.

ERIC Educational Resources Information Center

White, Lesley

1992-01-01

This paper explains the origin of the University of West Sidney's Bachelor of Applied Science in Social Ecology degree, and describes underlying philosophical framework, the major course organizing principles, and the proposed structure of the course. Highlights the problematic nature of setting up a dialectical, nondisciplinary-based program.…

Analysis of the tertiary structure of the ribonuclease P ribozyme-substrate complex by site-specific photoaffinity crosslinking.

PubMed Central

Harris, M E; Kazantsev, A V; Chen, J L; Pace, N R

1997-01-01

Bacterial ribonuclease P (RNase P), an endonuclease involved in tRNA maturation, is a ribonucleoprotein containing a catalytic RNA. The secondary structure of this ribozyme is well-established, and a low-resolution model of the three-dimensional structure of the ribozyme-substrate complex has been proposed based on site-specific crosslinking and phylogenetic comparative data [Harris ME et al., 1994 EMBO J 13:3953-3963]. However, several substructures of that model were poorly constrained by the available data. In the present analysis, additional constraints between elements within the Escherichia coli RNase P RNA-pre-tRNA complex were determined by intra- and intermolecular crosslinking experiments. Circularly permuted RNase P RNAs were used to position an azidophenacyl photoactive crosslinking agent specifically at strategic sites within the ribozyme-substrate complex. Crosslink sites were mapped by primer extension and confirmed by analysis of the mobility of the crosslinked RNA lariats on denaturing acrylamide gels relative to circular and linear RNA standards. Crosslinked species generally retained significant catalytic activity, indicating that the results reflect the native ribozyme structure. The crosslinking results support the general configuration of the structure model and predicate new positions and orientations for helices that were previously poorly constrained by the data set. The expanded library of crosslinking constraints was used, together with secondary and tertiary structure identified by phylogenetic sequence comparisons, to refine significantly the model of RNase P RNA with bound substrate pre-tRNA. The crosslinking results and data from chemical-modification and mutational studies are discussed in the context of the current structural perspective on this ribozyme. PMID:9174092

Effect of poly and mono-unsaturated fatty acids on stability and structure of recombinant S100A8/A9.

PubMed

Asghari, Hamideh; Chegini, Koorosh Goodarzvand; Amini, Abbas; Gheibi, Nematollah

2016-03-01

Recombinant pET 15b vectors containing the coding sequences S100A8 and S100A9 are expressed in Escherichia coli BL21 (DE3) and purified using Ni-NTA affinity chromatography. The structural changes of S100A8/A9 complex are analyzed upon interaction with poly/mono-unsaturated fatty acids (UFAs). The thermodynamic values, Gibbs free energy and the protein melting point, are obtained through thermal denaturation of protein both with and without UFAs by thermal scanning of protein emission using the fluorescence spectroscopy technique. The far-ultraviolet circular dichroism spectra show that all studied unsaturated fatty acids, including arachidonic, linoleic, alpha-linolenic and oleic acids, induce changes in the secondary structure of S100A8/A9 by reducing the α-helix and β-sheet structures. The tertiary structure of S100A8/A9 has fluctuations in the fluorescence emission spectra after the incubation of protein with UFAs. The blue-shift of emission maximum wavelength and the increase in fluorescence intensity of anilino naphthalene-8-sulfonic acid confirm that the partial unfolding is caused by the conformational changes in the tertiary structure in the presence of UFAs. The structural changes in S100A8/A9 and its lower stability in the presence of UFAs may be necessary for S100A8/A9 to play a biological role in the inflammatory milieu. Copyright © 2015 Elsevier B.V. All rights reserved.