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

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…

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

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.

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.

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.

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.

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.

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.

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.

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

Thioesterases: A new perspective based on their primary and tertiary structures

PubMed Central

Cantu, David C; Chen, Yingfei; Reilly, Peter J

2010-01-01

Thioesterases (TEs) are classified into EC 3.1.2.1 through EC 3.1.2.27 based on their activities on different substrates, with many remaining unclassified (EC 3.1.2.–). Analysis of primary and tertiary structures of known TEs casts a new light on this enzyme group. We used strong primary sequence conservation based on experimentally proved proteins as the main criterion, followed by verification with tertiary structure superpositions, mechanisms, and catalytic residue positions, to accurately define TE families. At present, TEs fall into 23 families almost completely unrelated to each other by primary structure. It is assumed that all members of the same family have essentially the same tertiary structure; however, TEs in different families can have markedly different folds and mechanisms. Conversely, the latter sometimes have very similar tertiary structures and catalytic mechanisms despite being only slightly or not at all related by primary structure, indicating that they have common distant ancestors and can be grouped into clans. At present, four clans encompass 12 TE families. The new constantly updated ThYme (Thioester-active enzYmes) database contains TE primary and tertiary structures, classified into families and clans that are different from those currently found in the literature or in other databases. We review all types of TEs, including those cleaving CoA, ACP, glutathione, and other protein molecules, and we discuss their structures, functions, and mechanisms. PMID:20506386

A constraint logic programming approach to associate 1D and 3D structural components for large protein complexes.

PubMed

Dal Palù, Alessandro; Pontelli, Enrico; He, Jing; Lu, Yonggang

2007-01-01

The paper describes a novel framework, constructed using Constraint Logic Programming (CLP) and parallelism, to determine the association between parts of the primary sequence of a protein and alpha-helices extracted from 3D low-resolution descriptions of large protein complexes. The association is determined by extracting constraints from the 3D information, regarding length, relative position and connectivity of helices, and solving these constraints with the guidance of a secondary structure prediction algorithm. Parallelism is employed to enhance performance on large proteins. The framework provides a fast, inexpensive alternative to determine the exact tertiary structure of unknown proteins.

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.

Automated extraction and classification of RNA tertiary structure cyclic motifs

PubMed Central

Lemieux, Sébastien; Major, François

2006-01-01

A minimum cycle basis of the tertiary structure of a large ribosomal subunit (LSU) X-ray crystal structure was analyzed. Most cycles are small, as they are composed of 3- to 5 nt, and repeated across the LSU tertiary structure. We used hierarchical clustering to quantify and classify the 4 nt cycles. One class is defined by the GNRA tetraloop motif. The inspection of the GNRA class revealed peculiar instances in sequence. First is the presence of UA, CA, UC and CC base pairs that substitute the usual sheared GA base pair. Second is the revelation of GNR(Xn)A tetraloops, where Xn is bulged out of the classical GNRA structure, and of GN/RA formed by the two strands of interior-loops. We were able to unambiguously characterize the cycle classes using base stacking and base pairing annotations. The cycles identified correspond to small and cyclic motifs that compose most of the LSU RNA tertiary structure and contribute to its thermodynamic stability. Consequently, the RNA minimum cycles could well be used as the basic elements of RNA tertiary structure prediction methods. PMID:16679452

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

Predicting loop–helix tertiary structural contacts in RNA pseudoknots

PubMed Central

Cao, Song; Giedroc, David P.; Chen, Shi-Jie

2010-01-01

Tertiary interactions between loops and helical stems play critical roles in the biological function of many RNA pseudoknots. However, quantitative predictions for RNA tertiary interactions remain elusive. Here we report a statistical mechanical model for the prediction of noncanonical loop–stem base-pairing interactions in RNA pseudoknots. Central to the model is the evaluation of the conformational entropy for the pseudoknotted folds with defined loop–stem tertiary structural contacts. We develop an RNA virtual bond-based conformational model (Vfold model), which permits a rigorous computation of the conformational entropy for a given fold that contains loop–stem tertiary contacts. With the entropy parameters predicted from the Vfold model and the energy parameters for the tertiary contacts as inserted parameters, we can then predict the RNA folding thermodynamics, from which we can extract the tertiary contact thermodynamic parameters from theory–experimental comparisons. These comparisons reveal a contact enthalpy (ΔH) of −14 kcal/mol and a contact entropy (ΔS) of −38 cal/mol/K for a protonated C+•(G–C) base triple at pH 7.0, and (ΔH = −7 kcal/mol, ΔS = −19 cal/mol/K) for an unprotonated base triple. Tests of the model for a series of pseudoknots show good theory–experiment agreement. Based on the extracted energy parameters for the tertiary structural contacts, the model enables predictions for the structure, stability, and folding pathways for RNA pseudoknots with known or postulated loop–stem tertiary contacts from the nucleotide sequence alone. PMID:20100813

[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.

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.

[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.

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

Molecular dynamics study of unfolding of lysozyme in water and its mixtures with dimethyl sulfoxide.

PubMed

Sedov, Igor A; Magsumov, Timur I

2017-09-01

All-atom explicit solvent molecular dynamics was used to study the process of unfolding of hen egg white lysozyme in water and mixtures of water with dimethyl sulfoxide at different compositions. We have determined the kinetic parameters of unfolding at a constant temperature 450K. For each run, the time of disruption of the tertiary structure of lysozyme t u was defined as the moment when a certain structural criterion computed from the trajectory reaches its critical value. A good agreement is observed between the results obtained using several different criteria. The secondary structure according to DSSP calculations is found to be partially unfolded to the moment of disruption of tertiary structure, but some of its elements keep for a long time after that. The values of t u averaged over ten 30ns-long trajectories for each solvent composition are shown to decrease very rapidly with addition of dimethyl sulfoxide, and rather small amounts of dimethyl sulfoxide are found to change the pathway of unfolding. In pure water, despite the loss of tertiary contacts and disruption of secondary structure elements, the protein preserves its compact globular state at least over 130ns of simulation, while even at 5mol percents of dimethyl sulfoxide it loses its compactness within 30ns. The proposed methodology is a generally applicable tool to quantify the rate of protein unfolding in simulation studies. Copyright © 2017 Elsevier Inc. 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.

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.

Relationship of PrPSc molecular properties with incubation time in a natural prion disease host: a characterization of three isolates of U.S. sheep scrapie

USDA-ARS?s Scientific Manuscript database

Determination of aspects of tertiary and quaternary structure of PrPSc associated with differences in disease presentation in the host is a key area of interest in the prion field. Previously, we determined that a U.S. scrapie isolate (136-VDEP) with a short incubation time upon passage in sheep als...

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.

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.

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

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.

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.

High-throughput determination of RNA structure by proximity ligation.

PubMed

Ramani, Vijay; Qiu, Ruolan; Shendure, Jay

2015-09-01

We present an unbiased method to globally resolve RNA structures through pairwise contact measurements between interacting regions. RNA proximity ligation (RPL) uses proximity ligation of native RNA followed by deep sequencing to yield chimeric reads with ligation junctions in the vicinity of structurally proximate bases. We apply RPL in both baker's yeast (Saccharomyces cerevisiae) and human cells and generate contact probability maps for ribosomal and other abundant RNAs, including yeast snoRNAs, the RNA subunit of the signal recognition particle and the yeast U2 spliceosomal RNA homolog. RPL measurements correlate with established secondary structures for these RNA molecules, including stem-loop structures and long-range pseudoknots. We anticipate that RPL will complement the current repertoire of computational and experimental approaches in enabling the high-throughput determination of secondary and tertiary RNA structures.

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

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.

Preliminary crystallographic studies of four crystal forms of serum albumin

NASA Technical Reports Server (NTRS)

Carter, D. C.; Chang, B.; Ho, J. X.; Keeling, K.; Krishnasami, Z.

1994-01-01

Several crystal forms of serum albumin suitable for three-dimensional structure determination have been grown. These forms include crystals of recombinant and wild-type human serum albumin, baboon serum albumin, and canine serum albumin. The intrinsic limits of X-ray diffraction for these crystals are in the range 0.28-0.22 nm. Two of the crystal forms produced from human and canine albumin include incorporated long-chain fatty acids. Molecular replacement experiments have been successfully conducted on each crystal form using the previously determined atomic coordinates of human serum albumin illustrating the conserved tertiary structure.

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

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.

Crystallographic and mutational analyses of tannase from Lactobacillus plantarum.

PubMed

Matoba, Yasuyuki; Tanaka, Naomi; Noda, Masafumi; Higashikawa, Fumiko; Kumagai, Takanori; Sugiyama, Masanori

2013-11-01

Tannin acylhydrolase (EC 3.1.1.20) referred commonly as tannase catalyzes the hydrolysis of the galloyl ester bond of tannins to release gallic acid. Although the enzyme is useful for various industries, the tertiary structure is not yet determined. In this study, we determined the crystal structure of tannase produced by Lactobacillus plantarum. The tannase structure belongs to a member of α/β-hydrolase superfamily with an additional "lid" domain. A glycerol molecule derived from cryoprotectant solution was accommodated into the tannase active site. The binding manner of glycerol to tannase seems to be similar to that of the galloyl moiety in the substrate. Copyright © 2013 Wiley Periodicals, Inc.

Adapting the academic motivation scale for use in pre-tertiary mathematics classrooms

NASA Astrophysics Data System (ADS)

Lim, Siew Yee; Chapman, Elaine

2015-09-01

The Academic Motivation Scale ( ams) is a comprehensive and widely used instrument for assessing motivation based on the self-determination theory. Currently, no such comprehensive instrument exists to assess the different domains of motivation (stipulated by the self-determination theory) in mathematics education at the pre-tertiary level (grades 11 and 12) in Asia. This study adapted the ams for this use and assessed the properties of the adapted instrument with 1610 students from Singapore. Exploratory and confirmatory factor analyses indicated a five-factor structure for the modified instrument (the three original ams intrinsic subscales collapsed into a single factor). Additionally, the modified instrument exhibited good internal consistency (mean α = .88), and satisfactory test-retest reliability over a 1-month interval (mean r xx = .73). The validity of the modified ams was further demonstrated through correlational analyses among scores on its subscales, and with scores on other instruments measuring mathematics attitudes, anxiety and achievement.

Highly Structured ePortfolio Platform for Bachelor of Nursing Students: Lessons Learned in Implementation

ERIC Educational Resources Information Center

Collins, Emma; O'Brien, Ray

2018-01-01

In 2015, the School of Nursing at Otago Polytechnic, a tertiary institution in Dunedin, New Zealand commenced using an ePortfolio platform with students in the Bachelor of Nursing program. A project was undertaken to evaluate the implementation of this technology and determine its ongoing use. This sequential, exploratory, mixed-methods research…

Administrative Strategies of Departmental Heads as Determinants for the Effective Management of Human Resources in Tertiary Institutions in Delta State, Nigeria

ERIC Educational Resources Information Center

Osakwe, Regina N.

2015-01-01

This study investigated administrative strategies of departmental heads as determinants of effective management of human resources in tertiary institutions. Four research questions were asked and four hypotheses were formulated to guide the study. As a descriptive survey, the population comprised all the eight tertiary institutions in the state…

Correlation between the radiological observation of isolated tertiary waves on an esophagram and findings on high-resolution esophageal manometry.

PubMed

Halland, M; Ravi, K; Barlow, J; Arora, A

2016-01-01

Barium esophagrams are a frequently performed test, and radiological observations about potential abnormal esophageal motility, such as tertiary contractions, are commonly reported. We sought to assess the correlation between tertiary waves, and in particular isolated tertiary waves, on esophagrams and findings on non-synchronous high-resolution esophageal manometry. We retrospectively reviewed reports of esophagrams performed at a tertiary referral center and identified patients in whom tertiary waves were observed and a high-resolution esophageal manometry had been performed. We defined two groups; group 1 was defined as patients with isolated tertiary waves, whereas group 2 had tertiary waves and evidence of achalasia or an obstructing structural abnormality on the esophagram. We collected data on demographics, dysphagia score, associated findings on esophagram, and need for intervention. We reviewed the reports of 2100 esophagrams of which tertiary waves were noted as an isolated abnormality in 92, and in association with achalasia or a structural obstruction in 61. High-resolution manometry was performed in 17 patients in group 1, and five had evidence of a significant esophageal motility disorder and 4 required any intervention. Twenty-one patients in group 2 underwent manometry, and 18 had a significant esophageal motility disorder. An isolated finding of tertiary waves on an esophagram is rarely associated with a significant esophageal motility disorder that requires intervention. All patients with isolated tertiary waves who required intervention had a dysphagia to liquids. Tertiary contractions, in the absence of dysphagia to liquids, indicate no significant esophageal motility disorder. © 2014 International Society for Diseases of the Esophagus.

Protein backbone engineering as a strategy to advance foldamers toward the frontier of protein-like tertiary structure.

PubMed

Reinert, Zachary E; Horne, W Seth

2014-11-28

A variety of non-biological structural motifs have been incorporated into the backbone of natural protein sequences. In parallel work, diverse unnatural oligomers of de novo design (termed "foldamers") have been developed that fold in defined ways. In this Perspective article, we survey foundational studies on protein backbone engineering, with a focus on alterations made in the context of complex tertiary folds. We go on to summarize recent work illustrating the potential promise of these methods to provide a general framework for the construction of foldamer mimics of protein tertiary structures.

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

The Policy Determinants of Investment in Tertiary Education. OECD Economics Department Working Papers, No. 576

ERIC Educational Resources Information Center

Martins, Joaquim Oliveira; Boarini, Romina; Strauss, Hubert; de la Maisonneuve, Christine; Saadi, Clarice

2007-01-01

This paper assesses how policies and institutions affect private returns to invest in tertiary human capital, the ability of individuals to finance this investment and the institutional characteristics of tertiary education systems. Focusing on core tertiary education services, the paper presents new measures of private returns to tertiary…

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

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

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,…

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.

HIGH LEVELS OF MONOAROMATIC COMPOUNDS LIMIT THE USE OF SOLID-PHASE MICROEXTRACTION OF METHYL TERTIARY BUTYL ETHER AND TERTIARY BUTYL ALCOHOL

EPA Science Inventory

Recently, two papers reported the use of solid-phase microextraction (SPME) with polydimethylsiloxane(PDMS)/Carboxen fibers to determine trace levels of methyl tertiary butyl ether (MTBE) and tertiary butyl alcohol (tBA) in water. Attempts were made to apply this technique to th...

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,…

Factors affecting utilization of university health services in a tertiary institution in South-West Nigeria.

PubMed

Obiechina, G O; Ekenedo, G O

2013-01-01

Most university health services have extensive health infrastructures, for the provision of effective and efficient health services to the students. In this study, we have tried to determine student's perception of factors affecting their utilization. To determine students' perception of health care services provided in a tertiary institution and assess students' attitude towards utilization. Simple random sampling technique was used to select 540 respondents, comprising of 390 males and 150 females. A structured and self-administered questionnaire was the instrument used to collect data for the study, while data collected was analyzed using descriptive statistics of frequency count and percentage. High cost of drugs (72.0%), non availability of essential drugs (54.8%), time spent waiting for treatment (67.2%), inadequate referral services (81.7%), and satisfaction with services (60.6%) were considered by the respondents as factors affecting the utilization of university health services. Students-medical staff relationship and accessibility to health facility (77.6% and 74.3% respectively) were, however, not considered as factors that affect utilization of university health services. It is recommended that to improve utilization and cost of care, government should make necessary efforts to incorporate tertiary institution into National Health Insurance scheme so that students above the age of 18 years can benefit from free treatment.

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.

Apolipoprotein AI tertiary structures determine stability and phospholipid-binding activity of discoidal high-density lipoprotein particles of different sizes

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

Chen, Bin; Ren, Xuefeng; Neville, Tracey

2009-05-18

Human high-density lipoprotein (HDL) plays a key role in the reverse cholesterol transport pathway that delivers excess cholesterol back to the liver for clearance. In vivo, HDL particles vary in size, shape and biological function. The discoidal HDL is a 140-240 kDa, disk-shaped intermediate of mature HDL. During mature spherical HDL formation, discoidal HDLs play a key role in loading cholesterol ester onto the HDL particles by activating the enzyme, lecithin:cholesterol acyltransferase (LCAT). One of the major problems for high-resolution structural studies of discoidal HDL is the difficulty in obtaining pure and, foremost, homogenous sample. We demonstrate here that themore » commonly used cholate dialysis method for discoidal HDL preparation usually contains 5-10% lipid-poor apoAI that significantly interferes with the high-resolution structural analysis of discoidal HDL using biophysical methods. Using an ultracentrifugation method, we quickly removed lipid-poor apoAI. We also purified discoidal reconstituted HDL (rHDL) into two pure discoidal HDL species of different sizes that are amendable for high-resolution structural studies. A small rHDL has a diameter of 7.6 nm, and a large rHDL has a diameter of 9.8 nm. We show that these two different sizes of discoidal HDL particles display different stability and phospholipid-binding activity. Interestingly, these property/functional differences are independent from the apoAI -helical secondary structure, but are determined by the tertiary structural difference of apoAI on different discoidal rHDL particles, as evidenced by two-dimensional NMR and negative stain electron microscopy data. Our result further provides the first high-resolution NMR data, demonstrating a promise of structural determination of discoidal HDL at atomic resolution using a combination of NMR and other biophysical techniques.« less

The 2.2 A resolution structure of the O(H) blood-group-specific lectin I from Ulex europaeus.

PubMed

Audette, G F; Vandonselaar, M; Delbaere, L T

2000-12-01

The tertiary and quaternary structure of the lectin I from Ulex europaeus (UE-I) has been determined to 2.2 A resolution. UE-I is a dimeric metalloglycoprotein that binds the H-type 2 human blood group determinant [alpha-L-Fucalpha(1-->2)-beta-D-Galbeta(1-->4)-beta-D-Glc NAcalpha-]. Nine changes from the published amino acid sequence were necessary to account for the electron density. The quaternary structural organization of UE-I is that of the most commonly occurring legume lectin dimer. The tertiary structure of the monomeric subunits is similar to that in the conventional lectin subunit; however, some structural differences are noted. These differences include a four-stranded anti-parallel "S" sheet in UE-I versus the five-stranded S sheet in other lectin monomers. The Ala residue of the Ala-Asp cis-peptide bond present in the carbohydrate-binding site of the conventional lectin monomer is replaced with a Thr in the UE-I structure. Also, a novel disulfide bridge linking Cys115 and Cys150 is present. There are two metallic ions, one calcium and the other manganese, per subunit. N-linked oligosaccharides are at residues 23 and 111 of each subunit. One molecule of R-2-methyl-2, 4-pentanediol (R-MPD) is present in a shallow depression on the surface of each subunit. In order to examine the binding of the H-type 2 blood group determinant by UE-I, its beta-methyl glycoside (H-type 2-OMe) was docked into the binding site of R-MPD. The epitope previously identified for H-type 2-OMe by chemical mapping proved, with only minor adjustment of amino acid residues, to be complementary to the shallow cavity occupied by R-MPD in the structure. Several key interactions have been proposed between the H-type 2-OMe and UE-I. Copyright 2000 Academic Press.

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

Equilibrium Ensembles for Insulin Folding from Bias-Exchange Metadynamics.

PubMed

Singh, Richa; Bansal, Rohit; Rathore, Anurag Singh; Goel, Gaurav

2017-04-25

Earliest events in the aggregation process, such as single molecule reconfiguration, are extremely important and the most difficult to characterize in experiments. To this end, we have used well-tempered bias exchange metadynamics simulations to determine the equilibrium ensembles of an insulin molecule under amyloidogenic conditions of low pH and high temperature. A bin-based clustering method that uses statistics accumulated in bias exchange metadynamics trajectories was employed to construct a detailed thermodynamic and kinetic model of insulin folding. The highest lifetime, lowest free-energy ensemble identified consisted of native conformations adopted by a folded insulin monomer in solution, namely, the R-, the R f -, and the T-states of insulin. The lowest free-energy structure had a root mean square deviation of only 0.15 nm from native x-ray structure. The second longest-lived metastable state was an unfolded, compact monomer with little similarity to the native structure. We have identified three additional long-lived, metastable states from the bin-based model. We then carried out an exhaustive structural characterization of metastable states on the basis of tertiary contact maps and per-residue accessible surface areas. We have also determined the lowest free-energy path between two longest-lived metastable states and confirm earlier findings of non-two-state folding for insulin through a folding intermediate. The ensemble containing the monomeric intermediate retained 58% of native hydrophobic contacts, however, accompanied by a complete loss of native secondary structure. We have discussed the relative importance of nativelike versus nonnative tertiary contacts for the folding transition. We also provide a simple measure to determine the importance of an individual residue for folding transition. Finally, we have compared and contrasted this intermediate with experimental data obtained in spectroscopic, crystallographic, and calorimetric measurements during early stages of insulin aggregation. We have also determined stability of monomeric insulin by incubation at a very low concentration to isolate protein-protein interaction effects. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

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…

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.

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.

Micelles for the self-assembly of "off-on-off" fluorescent sensors for pH windows.

PubMed

Diaz-Fernandez, Yuri; Foti, Francesco; Mangano, Carlo; Pallavicini, Piersandro; Patroni, Stefano; Perez-Gramatges, Aurora; Rodriguez-Calvo, Simon

2006-01-11

A micellar approach is proposed to build a series of systems featuring an "off-on-off" fluorescent window response with changes in pH. The solubilizing properties of micelles are used to self-assemble, in water, plain pyrene with lipophilized pyridine and tertiary amine moieties. Since these components are contained in the small volume of the same micelle, pyrene fluorescence is influenced by the basic moieties: protonated pyridines and free tertiary amines behave as quenchers. Accordingly, fluorescence transitions from the "off" to the "on" state, and viceversa, take place when the pH crosses the pK(a) values of the amine and pyridine fragments. To obtain an "off-on-off" fluorescent response in this investigation we use either a set of dibasic lipophilic molecules (containing covalently linked pyridine and tertiary amine groups) or combinations of separate, lipophilic pyridines and tertiary amines. The use of combinations of dibasic and monobasic lipophilic molecules also gives a window-shaped fluorescence response with changes in pH: it is the highest pyridine pK(a) and the lowest tertiary amine pK(a) that determine the window limits. The pK(a) values of all the examined lipophilic molecules were determined in micelles, and compared with the values found for the same molecules in solvent mixtures in which they are molecularly dispersed. The effect of micellization is to significantly lower the observed protonation constants of the lipophilized species. Moreover, the more lipophilic a molecule is, the lower the observed logK value is. Accordingly, changing the substituents on the basic moieties or modifying their structure, tuning the lipophilicity of the mono- or dibases, and choosing among a large set of possible combination of lipophilized mono- and dibases have allowed us to tune, almost at will, both the width and the position along the pH axis of the obtained fluorescent window.

Structure and Location of the Regulatory β Subunits in the (αβγδ)4 Phosphorylase Kinase Complex* ♦

PubMed Central

Nadeau, Owen W.; Lane, Laura A.; Xu, Dong; Sage, Jessica; Priddy, Timothy S.; Artigues, Antonio; Villar, Maria T.; Yang, Qing; Robinson, Carol V.; Zhang, Yang; Carlson, Gerald M.

2012-01-01

Phosphorylase kinase (PhK) is a hexadecameric (αβγδ)4 complex that regulates glycogenolysis in skeletal muscle. Activity of the catalytic γ subunit is regulated by allosteric activators targeting the regulatory α, β, and δ subunits. Three-dimensional EM reconstructions of PhK show it to be two large (αβγδ)2 lobes joined with D2 symmetry through interconnecting bridges. The subunit composition of these bridges was unknown, although indirect evidence suggested the β subunits may be involved in their formation. We have used biochemical, biophysical, and computational approaches to not only address the quaternary structure of the β subunits within the PhK complex, i.e. whether they compose the bridges, but also their secondary and tertiary structures. The secondary structure of β was determined to be predominantly helical by comparing the CD spectrum of an αγδ subcomplex with that of the native (αβγδ)4 complex. An atomic model displaying tertiary structure for the entire β subunit was constructed using chemical cross-linking, MS, threading, and ab initio approaches. Nearly all this model is covered by two templates corresponding to glycosyl hydrolase 15 family members and the A subunit of protein phosphatase 2A. Regarding the quaternary structure of the β subunits, they were directly determined to compose the four interconnecting bridges in the (αβγδ)4 kinase core, because a β4 subcomplex was observed through both chemical cross-linking and top-down MS of PhK. The predicted model of the β subunit was docked within the bridges of a cryoelectron microscopic density envelope of PhK utilizing known surface features of the subunit. PMID:22969083

Protein Folding and Self-Organized Criticality

NASA Astrophysics Data System (ADS)

Bajracharya, Arun; Murray, Joelle

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

Time-Resolved Hydroxyl Radical Footprinting of RNA with X-Rays.

PubMed

Hao, Yumeng; Bohon, Jen; Hulscher, Ryan; Rappé, Mollie C; Gupta, Sayan; Adilakshmi, Tadepalli; Woodson, Sarah A

2018-06-01

RNA footprinting by hydroxyl radical cleavage provides 'snapshots' of RNA tertiary structure or protein interactions that bury the RNA backbone. Generation of hydroxyl radicals with a high-flux synchrotron X-ray beam provides analysis on a short timescale (5-100 msec), which enables the structures of folding intermediates or other transient conformational states to be determined in biochemical solutions or cells. This article provides protocols for using synchrotron beamlines for hydroxyl radical footprinting. © 2018 by John Wiley & Sons, Inc. © 2018 John Wiley & Sons, Inc.

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

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.

Concerning the production of free radicals in proteins by ultraviolet light.

NASA Technical Reports Server (NTRS)

Androes, G. M.; Gloria, H. R.; Reinisch, R. F.

1972-01-01

The response to UV light of several solid proteins and model compounds has been studied in vacuum and at low temperature, using electron paramagnetic resonance techniques. The results indicate that the details of amino acid composition and sequence, and the tertiary structure of a protein are important in determining both the rate of, and the mechanism for, the production of free radicals, and in determining the conditions under which sulfur-type radicals can be produced. The results presented are related to enzyme inactivation and to the UV stability of proteins generally.

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

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.

Awareness about basic life support and emergency medical services and its associated factors among students in a tertiary care hospital in South India.

PubMed

Aroor, Akshatha Rao; Saya, Rama Prakash; Attar, Nazir Rahim; Saya, Ganesh Kumar; Ravinanthanan, Manikandan

2014-07-01

The knowledge and skills about the basic life support (BLS) and the advanced life support are the most important determining factors of the cardiopulmonary resuscitation (CPR) success rates. To determine the level of awareness on BLS and skills among undergraduate and postgraduate students of medical and dental profession, as well as nursing students and interns in a tertiary care hospital. This descriptive cross-sectional study was conducted in a tertiary care hospital in South India. The awareness level on BLS and factors associated which include age, sex, level of training (undergraduate, internship, and postgraduate groups), course of study (nursing, dental, and medical groups), and previous exposure to BLS were assessed by using a structured questionnaire. The association of these variables with awareness level was assessed by independent t test, analysis of variance, and linear regression analysis. Among 520 study subjects, 229 were students, 171 were interns, and 120 were postgraduate students. The overall mean score of awareness was 4.16 ± 1.40 (score range: 0-10). Age, sex, level of training, course of study, and previous exposure to BLS were significantly associated with awareness level in univariate analysis (P < 0.05). Linear regression model also showed that all the above variables were significantly associated with awareness level (P < 0.05). About 322 (61.9%) subjects attributed lack of awareness about BLS to lack of available professional training. About 479 (92.1%) responded that BLS training should be a part of medical curriculum. Awareness level on BLS is below average indicating the importance of professional training at all levels in a tertiary care health institution.

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.

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

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.

A novel endogenous inhibitor of phenoloxidase from Musca domestica has a cystine motif commonly found in snail and spider toxins.

PubMed

Daquinag, A C; Sato, T; Koda, H; Takao, T; Fukuda, M; Shimonishi, Y; Tsukamoto, T

1999-02-16

Phenoloxidase inhibitor (POI), found in the hemolymph of housefly pupae, is a novel dopa-containing and cystine-rich peptide that competitively inhibits phenoloxidase with a Ki in the nanomolar range. [Tyr32]POI is a potential precursor molecule also found in the hemolymph that may be posttranslationally oxidized to the dopa-containing peptide after creation of a rigid structure. By employing both a solid-phase peptide synthesis system based on a 9-fluorenylmethoxycarbonyl strategy and a specific air oxidation technique to ensure correct folding, we have been able to synthesize [Tyr32]POI. The synthetic [Tyr32]POI was confirmed to be identical to the native [Tyr32]POI by coelution high-performance liquid chromatography analysis and by enzymatic analysis using the phenoloxidase inhibition assay. To determine the disulfide pairings within the peptides, a series of enzyme hydrolyses and partial reduction/alkylation steps were performed. Three cystine pairs (Cys11-Cys25, Cys18-Cys29, and Cys24-Cys36) were determined by identification of the resulting peptides. The disulfide pairings of the two adjacent Cys residues (Cys11-Cys25 and Cys24-Cys36) were unambiguously assigned by comparing the derived fragments with the two possible isomers synthesized through a novel disulfide-linking technique. The arrangement of the disulfide bridges in POI was found to be topologically identical to those found for several peptides within the inhibitor cystine knot structural family. Although these peptides share a low primary sequence homology and display a diversity of biological functions, they nonetheless share similarities in their cystine motifs and tertiary structure. The tertiary structure model of POI, which was derived through molecular dynamics and energy minimization studies using restraints with determined disulfide connectivities, suggests that POI is a new class member of the inhibitor cystine-knot structural family.

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.

Ligand-induced folding of the thiM TPP riboswitch investigated by a structure-based fluorescence spectroscopic approach

PubMed Central

Lang, Kathrin; Rieder, Renate; Micura, Ronald

2007-01-01

Riboswitches are genetic control elements within non-coding regions of mRNA. They consist of a metabolite-sensitive aptamer and an adjoining expression platform. Here, we describe ligand-induced folding of a thiamine pyrophosphate (TPP) responsive riboswitch from Escherichia coli thiM mRNA, using chemically labeled variants. Referring to a recent structure determination of the TPP/aptamer complex, each variant was synthesized with a single 2-aminopurine (AP) nucleobase replacement that was selected to monitor formation of tertiary interactions of a particular region during ligand binding in real time by fluorescence experiments. We have determined the rate constants for conformational adjustment of the individual AP sensors. From the 7-fold differentiation of these constants, it can be deduced that tertiary contacts between the two parallel helical domains (P2/J3-2/P3/L3 and P4/P5/L5) that grip the ligand's ends in two separate pockets, form significantly faster than the function-critical three-way junction with stem P1 fully developed. Based on these data, we characterize the process of ligand binding by an induced fit of the RNA and propose a folding model of the TPP riboswitch aptamer. For the full-length riboswitch domain and for shorter constructs that represent transcriptional intermediates, we have additionally evaluated ligand-induced folding via AP-modified variants and provide insights into the sequential folding pathway that involves a finely balanced equilibrium of secondary structures. PMID:17693433

Determination of Cenozoic sedimentary structures using integrated geophysical surveys: A case study in the Barkol Basin, Xinjiang, China

NASA Astrophysics Data System (ADS)

Sun, Kai; Chen, Chao; Du, Jinsong; Wang, Limin; Lei, Binhua

2018-01-01

Thickness estimation of sedimentary basin is a complex geological problem, especially in an orogenic environment. Intense and multiple tectonic movements and climate changes result in inhomogeneity of sedimentary layers and basement configurations, which making sedimentary structure modelling difficult. In this study, integrated geophysical methods, including gravity, magnetotelluric (MT) sounding and electrical resistivity tomography (ERT), were used to estimate basement relief to understand the geological structure and evolution of the eastern Barkol Basin in China. This basin formed with the uplift of the eastern Tianshan during the Cenozoic. Gravity anomaly map revealed the framework of the entire area, and ERT as well as MT sections reflected the geoelectric features of the Cenozoic two-layer distribution. Therefore, gravity data, constrained by MT, ERT and boreholes, were utilized to estimate the spatial distribution of the Quaternary layer. The gravity effect of the Quaternary layer related to the Tertiary layer was later subtracted to obtain the residual anomaly for inversion. For the Tertiary layer, the study area was divided into several parts because of lateral difference of density contrasts. Gravity data were interpreted to determine the density contrast constrained by the MT results. The basement relief can be verified by geological investigation, including the uplift process and regional tectonic setting. The agreement between geophysical survey and prior information from geology emphasizes the importance of integrated geophysical survey as a complementary means of geological studies in this region.

[Illness behavior in chronic pain].

PubMed

Lavielle, Pilar; Clark, Patricia; Martínez, Homero; Mercado, Francisco; Ryan, Gery

2008-01-01

To describe the illness behaviour in patients with chronic pain. We conducted semi-structured interviews to 53 patients during 2000, in a tertiary care center. We explored their initial interpretations, responses and subsequent practices to chronic pain, until they received a diagnosis that satisfied them. Illness behaviour was determined by pain intensity and disability; beliefs regarding pain causes, trust in social networks, and quality and satisfaction with the health care systems. In terms of the decision to seek care, the first option was to go to the popular sector, followed by consulting a general physician, and as last resort, to go to a tertiary care center ("with a specialist"). Illness behaviour should be conceptualized as a process, which combines the use of different health care sectors by the same subjects, as a result of care provided sequentially by each previous sector.

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

Three-dimensional tertiary structure of yeast phenylalanine transfer RNA

NASA Technical Reports Server (NTRS)

Kim, S. H.; Sussman, J. L.; Suddath, F. L.; Quigley, G. J.; Mcpherson, A.; Wang, A. H. J.; Seeman, N. C.; Rich, A.

1974-01-01

Results of an analysis and interpretation of a 3-A electron density map of yeast phenylalanine transfer RNA. Some earlier detailed assignments of nucleotide residues to electron density peaks are found to be in error, even though the overall tracing of the backbone conformation of yeast phenylalanine transfer RNA was generally correct. A new, more comprehensive interpretation is made which makes it possible to define the tertiary interactions in the molecule. The new interpretation makes it possible to visualize a number of tertiary interactions which not only explain the structural role of most of the bases which are constant in transfer RNAs, but also makes it possible to understand in a direct and simple fashion the chemical modification data on transfer RNA. In addition, this pattern of tertiary interactions provides a basis for understanding the general three-dimensional folding of all transfer RNA molecules.

Adapting the Academic Motivation Scale for Use in Pre-Tertiary Mathematics Classrooms

ERIC Educational Resources Information Center

Lim, Siew Yee; Chapman, Elaine

2015-01-01

The Academic Motivation Scale (AMS) is a comprehensive and widely used instrument for assessing motivation based on the self-determination theory. Currently, no such comprehensive instrument exists to assess the different domains of motivation (stipulated by the self-determination theory) in mathematics education at the pre-tertiary level (grades…

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

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…

An Amino Acid Code to Define a Protein’s Tertiary Packing Surface

PubMed Central

Fraga, Keith J.; Joo, Hyun; Tsai, Jerry

2015-01-01

One difficult aspect of the protein-folding problem is characterizing the non-specific interactions that define packing in protein tertiary structure. To better understand tertiary structure, this work extends the knob-socket model by classifying the interactions of a single knob residue packed into a set of contiguous sockets, or a pocket made up of 4 or more residues. The knob-socket construct allows for a symbolic two-dimensional mapping of pockets. The two-dimensional mapping of pockets provides a simple method to investigate the variety of pocket shapes in order to understand the geometry of protein tertiary surfaces. The diversity of pocket geometries can be organized into groups of pockets that share a common core, which suggests that some interactions in pockets are ancillary to packing. Further analysis of pocket geometries displays a preferred configuration that is right-handed in α-helices and left-handed in β-sheets. The amino acid composition of pockets illustrates the importance of non-polar amino acids in packing as well as position specificity. As expected, all pocket shapes prefer to pack with hydrophobic knobs; however, knobs are not selective for the pockets they pack. Investigating side-chain rotamer preferences for certain pocket shapes uncovers no strong correlations. These findings allow a simple vocabulary based on knobs and sockets to describe protein tertiary packing that supports improved analysis, design and prediction of protein structure. PMID:26575337

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.

X-Ray Crystallography as a Tool to Determine Three-Dimensional Structures of Commercial Enzymes Subjected to Treatment in Pressurized Fluids.

PubMed

Feiten, Mirian Cristina; Di Luccio, Marco; Santos, Karine F; de Oliveira, Débora; Oliveira, J Vladimir

2017-06-01

The study of enzyme function often involves a multi-disciplinary approach. Several techniques are documented in the literature towards determining secondary and tertiary structures of enzymes, and X-ray crystallography is the most explored technique for obtaining three-dimensional structures of proteins. Knowledge of three-dimensional structures is essential to understand reaction mechanisms at the atomic level. Additionally, structures can be used to modulate or improve functional activity of enzymes by the production of small molecules that act as substrates/cofactors or by engineering selected mutants with enhanced biological activity. This paper presentes a short overview on how to streamline sample preparation for crystallographic studies of treated enzymes. We additionally revise recent developments on the effects of pressurized fluid treatment on activity and stability of commercial enzymes. Future directions and perspectives on the the role of crystallography as a tool to access the molecular mechanisms underlying enzymatic activity modulation upon treatment in pressurized fluids are also addressed.

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.

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.

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

Not Available

Phillips Petroleum Co. is poised to license its high conversion process to produce fuel ethers for blending in reformulated gasolines. The technology has been proven in a Phillips semiworks at Bartlesville, Okla. The process can produce methyl tertiary butyl ether, ethyl tertiary butyl ether, tertiary amyl methyl ether, or tertiary amyl ethyl ether with typical refinery process equipment and techniques. Phillips said it can achieve conversion levels of 92-99%, depending on the ether. The ether produced is determined by which hydrocarbon fraction is used for feedstock and which alcohol is chosen for reaction. The process is described.

The growth pattern of the human intestine and its mesentery.

PubMed

Soffers, Jelly H M; Hikspoors, Jill P J M; Mekonen, Hayelom K; Koehler, S Eleonore; Lamers, Wouter H

2015-08-22

It remains unclear to what extent midgut rotation determines human intestinal topography and pathology. We reinvestigated the midgut during its looping and herniation phases of development, using novel 3D visualization techniques. We distinguished 3 generations of midgut loops. The topography of primary and secondary loops was constant, but that of tertiary loops not. The orientation of the primary loop changed from sagittal to transverse due to the descent of ventral structures in a body with a still helical body axis. The 1st secondary loop (duodenum, proximal jejunum) developed intraabdominally towards a left-sided position. The 2nd secondary loop (distal jejunum) assumed a left-sided position inside the hernia before returning, while the 3rd and 4th secondary loops retained near-midline positions. Intestinal return into the abdomen resembled a backward sliding movement. Only after return, the 4th secondary loop (distal ileum, cecum) rapidly "slid" into the right lower abdomen. The seemingly random position of the tertiary small-intestinal loops may have a biomechanical origin. The interpretation of "intestinal rotation" as a mechanistic rather than a descriptive concept underlies much of the confusion accompanying the physiological herniation. We argue, instead, that the concept of "en-bloc rotation" of the developing midgut is a fallacy of schematic drawings. Primary, secondary and tertiary loops arise in a hierarchical fashion. The predictable position and growth of secondary loops is pre-patterned and determines adult intestinal topography. We hypothesize based on published accounts that malrotations result from stunted development of secondary loops.

Three critical hydrogen bonds determine the catalytic activity of the Diels–Alderase ribozyme

PubMed Central

Kraut, Stefanie; Bebenroth, Dirk; Nierth, Alexander; Kobitski, Andrei Y.; Nienhaus, G. Ulrich; Jäschke, Andres

2012-01-01

Compared to protein enzymes, our knowledge about how RNA accelerates chemical reactions is rather limited. The crystal structures of a ribozyme that catalyzes Diels–Alder reactions suggest a rich tertiary architecture responsible for catalysis. In this study, we systematically probe the relevance of crystallographically observed ground-state interactions for catalytic function using atomic mutagenesis in combination with various analytical techniques. The largest energetic contribution apparently arises from the precise shape complementarity between transition state and catalytic pocket: A single point mutant that folds correctly into the tertiary structure but lacks one H-bond that normally stabilizes the pocket is completely inactive. In the rate-limiting chemical step, the dienophile is furthermore activated by two weak H-bonds that contribute ∼7–8 kJ/mol to transition state stabilization, as indicated by the 25-fold slower reaction rates of deletion mutants. These H-bonds are also responsible for the tight binding of the Diels–Alder product by the ribozyme that causes product inhibition. For high catalytic activity, the ribozyme requires a fine-tuned balance between rigidity and flexibility that is determined by the combined action of one inter-strand H-bond and one magnesium ion. A sharp 360° turn reminiscent of the T-loop motif observed in tRNA is found to be important for catalytic function. PMID:21976731

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.

Elucidating Peptide and Protein Structure and Dynamics: UV Resonance Raman Spectroscopy

PubMed Central

Oladepo, Sulayman A.; Xiong, Kan; Hong, Zhenmin; Asher, Sanford A.

2011-01-01

UV resonance Raman spectroscopy (UVRR) is a powerful method that has the requisite selectivity and sensitivity to incisively monitor biomolecular structure and dynamics in solution. In this perspective, we highlight applications of UVRR for studying peptide and protein structure and the dynamics of protein and peptide folding. UVRR spectral monitors of protein secondary structure, such as the Amide III3 band and the Cα-H band frequencies and intensities can be used to determine Ramachandran Ψ angle distributions for peptide bonds. These incisive, quantitative glimpses into conformation can be combined with kinetic T-jump methodologies to monitor the dynamics of biomolecular conformational transitions. The resulting UVRR structural insight is impressive in that it allows differentiation of, for example, different α-helix-like states that enable differentiating π- and 310- states from pure α-helices. These approaches can be used to determine the Gibbs free energy landscape of individual peptide bonds along the most important protein (un)folding coordinate. Future work will find spectral monitors that probe peptide bond activation barriers that control protein (un)folding mechanisms. In addition, UVRR studies of sidechain vibrations will probe the role of side chains in determining protein secondary, tertiary and quaternary structures. PMID:21379371

Geophysical Investigation of Avon Valley, West-Central Montana, using Gravity and Seismic Reflection Profiling

NASA Astrophysics Data System (ADS)

Knatterud, L.; Mosolf, J.; Speece, M. A.; Zhou, X.

2014-12-01

The Avon Valley and adjacent mountains in west-central Montana lie within the Lewis and Clark Line, a major system of WNW-striking faults and folds that transect the more northerly structural grain of the northern Rockies and represent alternating episodes of transtensional and transpressional deformation. The northwest-trending valley has been previously interpreted as an extensional half graben filled with Tertiary sedimentary and volcanic deposits; however, little-to-no geophysical constraints on basin architecture or the thickness of Tertiary fill have been reported. A major northwest-striking fault with significant normal displacement clearly bounds the valley to the northeast, juxtaposing Tertiary sedimentary deposits against Proterozoic-Mesozoic units deformed by shortening structures and crosscut by Cretaceous granitic intrusions. Tertiary volcanic deposits unconformably overlying faulted and folded Phanerozoic-Proterozoic sequences in the eastern Garnet Range bound the valley to the southwest, but in the past no faults had been mapped along this margin. New mapping by the Montana Bureau of Mines and Geology (MBMG) has identified a system of high-angle, northwest- and northeast-striking, oblique-slip faults along the southwest border of the Avon calling into question if the valley is a half, full, or asymmetrical graben. Geophysical data has recently been acquired by Montana Tech to help define the structural architecture of the Avon Valley and the thickness of its Tertiary fill. Gravity data and a short seismic reflection profile have been collected and a preliminary interpretation of these data indicates a half graben with a series of normal faults bounding the western side of the valley. Ongoing gravity data collection throughout 2014 should refine this interpretation by better defining the bedrock-Tertiary interface at depth.

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

Impaired insulin signaling pathway in ovarian follicles of cows with cystic ovarian disease.

PubMed

Hein, G J; Panzani, C G; Rodríguez, F M; Salvetti, N R; Díaz, P U; Gareis, N C; Benítez, G A; Ortega, H H; Rey, F

2015-05-01

Cystic ovarian disease (COD) is an important cause of infertility in dairy cattle. Follicular cell steroidogenesis and proliferation in ovulatory follicles is stimulated by hormones such as insulin and its necessary post-receptor response. The aim of this study was to determine the expression of insulin receptor (IR), IR substrate-1 (IRS1) and phosphatidylinositol 3-kinase (PI3K), key intermediates in the insulin pathway, in control cows and cows with spontaneous COD and ACTH-induced COD. IR and IRS1 mRNA levels were greater in granulosa cells and lower in follicular cysts than in control tertiary follicles. PI3K mRNA levels were similar in all follicles evaluated, whereas the expression of IR, IRS1 and PI3K was similar in theca cells. Protein expression of IR was higher in control tertiary follicles than in the same structures in animals with COD and with cysts. IRS1 and PI3K protein expression showed the same pattern in tertiary and cystic follicles. However, the protein expression of subunit alpha p85 of PI3K was greater in theca cells from tertiary follicles than in cystic follicles. These results provide new insights into the insulin response in cows with COD. The lower gene and protein expressions of some insulin downstream effectors at an early stage of the signaling pathway could negatively influence the functionality of ovaries and contribute to follicle persistence. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

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.

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

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

[Study of selegiline and related compounds with x-ray diffraction].

PubMed

Simon, K; Böcskei, Z; Török, Z

1992-09-01

Selegiline and its parent compounds were studied by X-ray diffraction. It was established that the racemates of primary and secondary amines (p-fluoro-amphetamine, methamphetamine, p-fluoro-methamphetamine) hydrochloride do not form racemic compounds but crystalline as conglomerates, at the same time tertiary amines like selegiline and p-fluoro-selegiline hydrochlorides do. The crystalline structure of five enantiomeric hydrochlorides were determined, the CPhe-C-C-N torsion angle is anti-periplanar in all cases but in p-fluoro-amphetamine where it is gauche.

Recognition of coarse-grained protein tertiary structure.

PubMed

Lezon, Timothy; Banavar, Jayanth R; Maritan, Amos

2004-05-15

A model of the protein backbone is considered in which each residue is characterized by the location of its C(alpha) atom and one of a discrete set of conformal (phi, psi) states. We investigate the key differences between a description that offers a locally precise fit to known backbone structures and one that provides a globally accurate fit to protein structures. Using a statistical scoring scheme and threading, a protein's local best-fit conformation is highly recognizable, but its global structure cannot be directly determined from an amino acid sequence. The incorporation of information about the conformal states of neighboring residues along the chain allows one to accurately translate the local structure into a global structure. We present a two-step algorithm, which recognizes up to 95% of the tested protein native-state structures to within a 2.5 A root mean square deviation. Copyright 2004 Wiley-Liss, Inc.

Stratigraphy and structure of coalbed methane reservoirs in the United States: an overview

USGS Publications Warehouse

Pashin, J.C.

1998-01-01

Stratigraphy and geologic structure determine the shape, continuity and permeability of coal and are therefore critical considerations for designing exploration and production strategies for coalbed methane. Coal in the United states is dominantly of Pennsylvanian, Cretaceous and Tertiary age, and to date, more than 90% of the coalbed methane produced is from Pennsylvanian and cretaceous strata of the Black Warrior and San Juan Basins. Investigations of these basins establish that sequence stratigraphy is a promising approach for regional characterization of coalbed methane reservoirs. Local stratigraphic variation within these strata is the product of sedimentologic and tectonic processes and is a consideration for selecting completion zones. Coalbed methane production in the United States is mainly from foreland and intermontane basins containing diverse compression and extensional structures. Balanced structural models can be used to construct and validate cross sections as well as to quantify layer-parallel strain and predict the distribution of fractures. Folds and faults influence gas and water production in diverse ways. However, interwell heterogeneity related to fractures and shear structures makes the performance of individual wells difficult to predict.Stratigraphy and geologic structure determine the shape, continuity and permeability of coal and are therefore critical considerations for designing exploration and production strategies for coalbed methane. Coal in the United States is dominantly of Pennsylvanian, Cretaceous and Tertiary age, and to date, more than 90% of the coalbed methane produced is from Pennsylvanian and Cretaceous strata of the Black Warrior and San Juan Basins. Investigations of these basins establish that sequence stratigraphy is a promising approach for regional characterization of coalbed methane reservoirs. Local stratigraphic variation within these strata is the product of sedimentologic and tectonic processes and is a consideration for selecting completion zones. Coalbed methane production in the United States is mainly from foreland and intermontane basins containing diverse compressional and extensional structures. Balanced structural models can be used to construct and validate cross sections as well as to quantify layer-parallel strain and predict the distribution of fractures. Folds and faults influence gas and water production in diverse ways. However, interwell heterogeneity related to fractures and shear structures makes the performance of individual wells difficult to predict.

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.

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

Tertiary structure of human {Lambda}6 light chains.

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

Pokkuluri, P. R.; Solomon, A.; Weiss, D. T.

1999-01-01

AL amyloidosis is a disease process characterized by the pathologic deposition of monoclonal light chains in tissue. To date, only limited information has been obtained on the molecular features that render such light chains amyloidogenic. Although protein products of the major human V kappa and V lambda gene families have been identified in AL deposits, one particular subgroup--lambda 6--has been found to be preferentially associated with this disease. Notably, the variable region of lambda 6 proteins (V lambda 6) has distinctive primary structural features including the presence in the third framework region (FR3) of two additional amino acid residues thatmore » distinguish members of this subgroup from other types of light chains. However, the structural consequences of these alterations have not been elucidated. To determine if lambda 6 proteins possess unique tertiary structural features, as compared to light chains of other V lambda subgroups, we have obtained x-ray diffraction data on crystals prepared from two recombinant V lambda 6 molecules. These components, isolated from a bacterial expression system, were generated from lambda 6-related cDNAs cloned from bone marrow-derived plasma cells from a patient (Wil) who had documented AL amyloidosis and another (Jto) with multiple myeloma and tubular cast nephropathy, but no evident fibrillar deposits. The x-ray crystallographic analyses revealed that the two-residue insertion located between positions 68 and 69 (not between 66 and 67 as previously surmised) extended an existing loop region that effectively increased the surface area adjacent to the first complementarity determining region (CDR1). Further, an unusual interaction between the Arg 25 and Phe 2 residues commonly found in lambda 6 molecules was noted. However, the structures of V lambda 6 Wil and Jto also differed from each other, as evidenced by the presence in the latter of certain ionic and hydrophobic interactions that we posit increased protein stability and thus prevented amyloid formation.« less

Ar-40 to Ar-39 ages of the large impact structures Kara and Manicouagan and their relevance to the Cretaceous-Tertiary and the Triassic-Jurassic boundary

NASA Technical Reports Server (NTRS)

Trieloff, M.; Jessberger, E. K.

1992-01-01

Since the discovery of the Ir enrichment in Cretaceous-Tertiary boundary clays in 1980, the effects of a 10-km asteroid impacting on the Earth 65 Ma ago have been discussed as the possible reason for the mass extinction--including the extinction of the dinosaurs--at the end of the Cretaceous. But up to now no crater of this age that is large enough (ca. 200 km in diameter) has been found. One candidate is the Kara Crater in northern Siberia. Kolesnikov et al. determined a K-Ar isochron of 65.6 +/- 0.5 Ma, indistinguishable from the age of the K-T boundary and interpreted this as confirmation of earlier proposals that the Kara bolide would have been at least one of the K-T impactors. Koeberl et al. determined Ar-40 to Ar-39 ages ranging from 70 to 82 Ma and suggested an association to the Campanian-Maastrichtian boundary, another important extinction horizon 73 Ma ago. We dated four impact melts, KA2-306, KA2-305, SA1-302, and AN9-182. Results from the investigation are discussed.

Ar-40 to Ar-39 ages of the large impact structures Kara and Manicouagan and their relevance to the Cretaceous-Tertiary and the Triassic-Jurassic boundary

NASA Astrophysics Data System (ADS)

Trieloff, M.; Jessberger, E. K.

Since the discovery of the Ir enrichment in Cretaceous-Tertiary boundary clays in 1980, the effects of a 10-km asteroid impacting on the Earth 65 Ma ago have been discussed as the possible reason for the mass extinction--including the extinction of the dinosaurs--at the end of the Cretaceous. But up to now no crater of this age that is large enough (ca. 200 km in diameter) has been found. One candidate is the Kara Crater in northern Siberia. Kolesnikov et al. determined a K-Ar isochron of 65.6 +/- 0.5 Ma, indistinguishable from the age of the K-T boundary and interpreted this as confirmation of earlier proposals that the Kara bolide would have been at least one of the K-T impactors. Koeberl et al. determined Ar-40 to Ar-39 ages ranging from 70 to 82 Ma and suggested an association to the Campanian-Maastrichtian boundary, another important extinction horizon 73 Ma ago. We dated four impact melts, KA2-306, KA2-305, SA1-302, and AN9-182. Results from the investigation are discussed.

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…

Prediction of conformational changes by single mutation in the hepatitis B virus surface antigen (HBsAg) identified in HBsAg-negative blood donors.

PubMed

Ie, Susan I; Thedja, Meta D; Roni, Martono; Muljono, David H

2010-11-18

Selection of hepatitis B virus (HBV) by host immunity has been suggested to give rise to variants with amino acid substitutions at or around the 'a' determinant of the surface antigen (HBsAg), the main target of antibody neutralization and diagnostic assays. However, there have never been successful attempts to provide evidence for this hypothesis, partly because the 3 D structure of HBsAg molecules has not been determined. Tertiary structure prediction of HBsAg solely from its primary amino acid sequence may reveal the molecular energetic of the mutated proteins. We carried out this preliminary study to analyze the predicted HBsAg conformation changes of HBV variants isolated from Indonesian blood donors undetectable by HBsAg assays and its significance, compared to other previously-reported variants that were associated with diagnostic failure. Three HBV variants (T123A, M133L and T143M) and a wild type sequence were analyzed together with frequently emerged variants T123N, M133I, M133T, M133V, and T143L. Based on the Jameson-Wolf algorithm for calculating antigenic index, the first two amino acid substitutions resulted in slight changes in the antigenicity of the 'a' determinant, while all four of the comparative variants showed relatively more significant changes. In the pattern T143M, changes in antigenic index were more significant, both in its coverage and magnitude, even when compared to variant T143L. These data were also partially supported by the tertiary structure prediction, in which the pattern T143M showed larger shift in the HBsAg second loop structure compared to the others. Single amino acid substitutions within or near the 'a' determinant of HBsAg may alter antigenicity properties of variant HBsAg, which can be shown by both its antigenic index and predicted 3 D conformation. Findings in this study emphasize the significance of variant T143M, the prevalent isolate with highest degree of antigenicity changes found in Indonesian blood donors. This highlights the importance of evaluating the effects of protein structure alterations on the sensitivity of screening methods being used in detection of ongoing HBV infection, as well as the use of vaccines and immunoglobulin therapy in contributing to the selection of HBV variants.

In silico insights into protein-protein interactions and folding dynamics of the saposin-like domain of Solanum tuberosum aspartic protease.

PubMed

De Moura, Dref C; Bryksa, Brian C; Yada, Rickey Y

2014-01-01

The plant-specific insert is an approximately 100-residue domain found exclusively within the C-terminal lobe of some plant aspartic proteases. Structurally, this domain is a member of the saposin-like protein family, and is involved in plant pathogen defense as well as vacuolar targeting of the parent protease molecule. Similar to other members of the saposin-like protein family, most notably saposins A and C, the recently resolved crystal structure of potato (Solanum tuberosum) plant-specific insert has been shown to exist in a substrate-bound open conformation in which the plant-specific insert oligomerizes to form homodimers. In addition to the open structure, a closed conformation also exists having the classic saposin fold of the saposin-like protein family as observed in the crystal structure of barley (Hordeum vulgare L.) plant-specific insert. In the present study, the mechanisms of tertiary and quaternary conformation changes of potato plant-specific insert were investigated in silico as a function of pH. Umbrella sampling and determination of the free energy change of dissociation of the plant-specific insert homodimer revealed that increasing the pH of the system to near physiological levels reduced the free energy barrier to dissociation. Furthermore, principal component analysis was used to characterize conformational changes at both acidic and neutral pH. The results indicated that the plant-specific insert may adopt a tertiary structure similar to the characteristic saposin fold and suggest a potential new structural motif among saposin-like proteins. To our knowledge, this acidified PSI structure presents the first example of an alternative saposin-fold motif for any member of the large and diverse SAPLIP family.

Genome-scale characterization of RNA tertiary structures and their functional impact by RNA solvent accessibility prediction.

PubMed

Yang, Yuedong; Li, Xiaomei; Zhao, Huiying; Zhan, Jian; Wang, Jihua; Zhou, Yaoqi

2017-01-01

As most RNA structures are elusive to structure determination, obtaining solvent accessible surface areas (ASAs) of nucleotides in an RNA structure is an important first step to characterize potential functional sites and core structural regions. Here, we developed RNAsnap, the first machine-learning method trained on protein-bound RNA structures for solvent accessibility prediction. Built on sequence profiles from multiple sequence alignment (RNAsnap-prof), the method provided robust prediction in fivefold cross-validation and an independent test (Pearson correlation coefficients, r, between predicted and actual ASA values are 0.66 and 0.63, respectively). Application of the method to 6178 mRNAs revealed its positive correlation to mRNA accessibility by dimethyl sulphate (DMS) experimentally measured in vivo (r = 0.37) but not in vitro (r = 0.07), despite the lack of training on mRNAs and the fact that DMS accessibility is only an approximation to solvent accessibility. We further found strong association across coding and noncoding regions between predicted solvent accessibility of the mutation site of a single nucleotide variant (SNV) and the frequency of that variant in the population for 2.2 million SNVs obtained in the 1000 Genomes Project. Moreover, mapping solvent accessibility of RNAs to the human genome indicated that introns, 5' cap of 5' and 3' cap of 3' untranslated regions, are more solvent accessible, consistent with their respective functional roles. These results support conformational selections as the mechanism for the formation of RNA-protein complexes and highlight the utility of genome-scale characterization of RNA tertiary structures by RNAsnap. The server and its stand-alone downloadable version are available at http://sparks-lab.org. © 2016 Yang et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

In Silico Insights into Protein-Protein Interactions and Folding Dynamics of the Saposin-Like Domain of Solanum tuberosum Aspartic Protease

PubMed Central

De Moura, Dref C.; Bryksa, Brian C.; Yada, Rickey Y.

2014-01-01

The plant-specific insert is an approximately 100-residue domain found exclusively within the C-terminal lobe of some plant aspartic proteases. Structurally, this domain is a member of the saposin-like protein family, and is involved in plant pathogen defense as well as vacuolar targeting of the parent protease molecule. Similar to other members of the saposin-like protein family, most notably saposins A and C, the recently resolved crystal structure of potato (Solanum tuberosum) plant-specific insert has been shown to exist in a substrate-bound open conformation in which the plant-specific insert oligomerizes to form homodimers. In addition to the open structure, a closed conformation also exists having the classic saposin fold of the saposin-like protein family as observed in the crystal structure of barley (Hordeum vulgare L.) plant-specific insert. In the present study, the mechanisms of tertiary and quaternary conformation changes of potato plant-specific insert were investigated in silico as a function of pH. Umbrella sampling and determination of the free energy change of dissociation of the plant-specific insert homodimer revealed that increasing the pH of the system to near physiological levels reduced the free energy barrier to dissociation. Furthermore, principal component analysis was used to characterize conformational changes at both acidic and neutral pH. The results indicated that the plant-specific insert may adopt a tertiary structure similar to the characteristic saposin fold and suggest a potential new structural motif among saposin-like proteins. To our knowledge, this acidified PSI structure presents the first example of an alternative saposin-fold motif for any member of the large and diverse SAPLIP family. PMID:25188221

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

Structure and Orientation of T4 Lysozyme Bound to the Small Heat Shock Protein α-Crystallin

PubMed Central

Claxton, Derek P.; Zou, Ping; Mchaourab, Hassane S.

2008-01-01

Summary We have determined the structural changes that accompany the formation of a stable complex between a destabilized mutant of T4 lysozyme (T4L) and the small heat-shock protein α-crystallin. Using pairs of fluorescence or spin label probes to fingerprint the T4L tertiary fold, we demonstrate that binding disrupts tertiary packing in the two domains as well as across the active site cleft. Furthermore, increased distances between i and i+4 residues of helices support a model in which the bound structure is not native-like but significantly unfolded. In the confines of the oligomer, T4L has a preferential orientation with residues in the more hydrophobic C-terminal domain sequestered in a buried environment while residues in the N-terminal domain are exposed to the aqueous solvent. Furthermore, EPR spectral lineshapes of sites in the N-terminal domain are narrower than in the folded, unbound T4L reflecting an unstructured backbone and an asymmetric pattern of contacts between T4L and α-crystallin. The net orientation is not affected by the location of the destabilizing mutation consistent with the notion that binding is not triggered by recognition of localized unfolding. Together, the structural and thermodynamic data indicate that the stably bound conformation of T4L is unfolded and support a model in which the two-modes of substrate binding originate from two discrete binding sites on the chaperone. PMID:18062989

Investigation on the pH-dependent binding of benzocaine and lysozyme by fluorescence and absorbance

NASA Astrophysics Data System (ADS)

Li, Shihui; Li, Daojin

2011-11-01

The interaction mechanism between benzocaine (BZC) and lysozyme (Lys) has been investigated by fluorescence, synchronous fluorescence, ultraviolet-vis (UV) absorption spectra, and three-dimensional fluorescence (3-D) in various pH medium. The observations of fluorescence spectra were mainly rationalized in terms of a static quenching process at lower concentration of BZC ( CBZC/ CLys < 9) and a combined quenching process at higher concentration of BZC ( CBZC/ CLys > 9) at pH 7.4 and 8.4. However, the fluorescence quenching was mainly arisen from static quenching by complex formation in all studied drug concentrations at pH 3.5. The structural characteristics of BZC and Lys were probed, and their binding affinities were determined under different pH conditions (pH 3.5, 7.4, and 8.4). The results indicated that the binding abilities of BZC to Lys decreased at the pH below and above the simulative physiological condition (pH 7.4) due to the alterations of the protein secondary and tertiary structures or the structural change of BZC. The effect of BZC on the conformation of Lys was analyzed using UV, synchronous fluorescence and three-dimensional fluorescence under different pH conditions. These results indicate that the binding of BZC to Lys causes apparent change in the secondary and tertiary structures of Lys. The effect of Zn 2+ on the binding constant of BZC with Lys under various pH conditions (pH 3.5, 7.4, and 8.4) was also studied.

Cervical spine injuries, mechanisms, stability and AIS scores from vertical loading applied to military environments.

PubMed

Yoganandan, Narayan; Pintar, Frank A; Humm, John R; Maiman, Dennis J; Voo, Liming; Merkle, Andrew

2016-07-01

The purpose of this study was to determine injuries to osteo-ligamentous structures of cervical column, mechanisms, forces, severities and AIS scores from vertical accelerative loading. Seven human cadaver head-neck complexes (56.9 ± 9.5 years) were aligned based on seated the posture of military soldiers. Army combat helmets were used. Specimens were attached to a vertical accelerator to apply caudo-cephalad g-forces. They were accelerated with increasing insults. Intermittent palpation and radiography were done. A roof structure mimicking military vehicle interior was introduced after a series of tests and experiments were conducted following similar protocols. Upon injury detection, CT and dissection were done. Temporal force responses were extracted, peak forces and times of occurrence were obtained, injury severities were graded, and spine stability was determined. Injuries occurred in tests only when the roof structure was included. Responses were tri-phasic: initial thrust, secondary tensile, tertiary roof contact phases. Peak forces: 1364-4382 N, initial thrust, 165-169 N, secondary tensile, 868-3368 N tertiary helmet-head roof contact phases. Times of attainments: 5.3-9.6, 31.7-42.6, 55.0-70.8 ms. Injuries included fractures and joint disruptions. Multiple injuries occurred in all but one specimen. A majority of injury severities were AIS = 2. Spines were considered unstable in a majority of cases. Spine response was tri-phasic. Injuries occurred in roof contact tests with the helmeted head-neck specimen. Multiplicity and unstable nature of AIS = 2 level injuries, albeit at lower severities, might predispose the spine to long-term accelerated degenerative changes. Clinical protocols should include a careful evaluation of sub-catastrophic injuries in military patients.

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

Extremophiles: developments of their special functions and potential resources.

PubMed

Fujiwara, Shinsuke

2002-01-01

Extremophilles are valuable resources in biotechnology. Enzymes from extremophiles are expected to fill the gap between biological and chemical processes due to their unusual properties. Especially enzymes from hyperthermophiles that can grow at above 90 degrees C were devoted owing to its extraordinary thermostability and denaturant tolerance. Screening trials of hyperthermophilic microorganisms were performed by a number of microbiologists and various unique strains were isolated from natural environments. One of the most successful uses of thermostable enzymes was DNA polymerase in the polymerase chain reaction (PCR). Thermostable enzymes are used in the chemical, food, pharmaceutical, paper and textile industries. Recombinant forms of thermostable enzymes that have been expressed in Escherichia coli are commonly utilized in industrial applications however their enzymatic characteristics and tertiary structure are different from the native ones produced in the original strains. In vitro heat treatment induces a structural conversion of the recombinant protein to its natural form. High temperature itself plays an important role in determining the specific characteristics and tertiary structure of the enzyme. Recent studies have revealed that hyperthermophiles can grow under numerous conditions not only in geothermal or deep-sea thermal environments. Technological advances have allowed DNA to be isolated from natural environments. Now genes could be isolated from microorganisms that have not been cultured. In this review, innovative approaches to hunt genes from natural environments without pure culturing of microorganisms are also discussed.

Preliminary results of potassium-argon age determinations from the Ugashik quadrangle, Alaska Peninsula: A section in The United States Geological Survey in Alaska: Accomplishments during 1980

USGS Publications Warehouse

Wilson, Frederic H.; Shew, Nora B.

1982-01-01

Early and preliminary results of potassiumargon dating work on samples from 12 sites in the Ugashik quadrangle indicate a continuation of the geologic trends seen in the Chignik and Sutwik Island quadrangles to the south (Wilson, 1980). Tertiary volcanic and hypabyssal rocks apparently fall into two age groups: early Tertiary-late Eocene to earliest Miocene and late Tertiary and Quaternary-late Miocene to Holocene (fig. 53).

Expansion tunnel performance with and without an electromagnetically opened tertiary diaphragm

NASA Technical Reports Server (NTRS)

Miller, C. G.

1977-01-01

A study was conducted to examine the effect of synchronization of an electromagnetically opened tertiary diaphragm with flow arrival at the diaphragm on the pitot pressure measured at the test section of an expansion tunnel. The effect of tertiary diaphragm pressure ratio (ratio of initial nozzle pressure to quiescent acceleration section pressure) on the pitot pressure time history is also determined. The inadequacy of a pressure transducer protection arrangement used in previous expansion tube and expansion tunnel tests was revealed.

DERMAL, ORAL, AND INHALATION PHARMACOKINETICS OF METHYL TERTIARY BUTYL ETHER (MTBE) IN HUMAN VOLUNTEERS

EPA Science Inventory

Methyl tertiary butyl ether (MTBE), a gasoline additive, used to increase octane and reduce carbon monoxide emissions and ozone precursors has contaminated drinking water leading to exposure by oral, inhalation, and dermal routes. To determine its dermal, oral, and inhalation ki...

Structural properties of matrix metalloproteinases.

PubMed

Bode, W; Fernandez-Catalan, C; Tschesche, H; Grams, F; Nagase, H; Maskos, K

1999-04-01

Matrix metalloproteinases (MMPs) are involved in extracellular matrix degradation. Their proteolytic activity must be precisely regulated by their endogenous protein inhibitors, the tissue inhibitors of metalloproteinases (TIMPs). Disruption of this balance results in serious diseases such as arthritis, tumour growth and metastasis. Knowledge of the tertiary structures of the proteins involved is crucial for understanding their functional properties and interference with associated dysfunctions. Within the last few years, several three-dimensional MMP and MMP-TIMP structures became available, showing the domain organization, polypeptide fold and main specificity determinants. Complexes of the catalytic MMP domains with various synthetic inhibitors enabled the structure-based design and improvement of high-affinity ligands, which might be elaborated into drugs. A multitude of reviews surveying work done on all aspects of MMPs have appeared in recent years, but none of them has focused on the three-dimensional structures. This review was written to close the gap.

Structural Basis for Sialoglycan Binding by the Streptococcus sanguinis SrpA Adhesin*♦

PubMed Central

Bensing, Barbara A.; Loukachevitch, Lioudmila V.; McCulloch, Kathryn M.; Yu, Hai; Vann, Kendra R.; Wawrzak, Zdzislaw; Anderson, Spencer; Chen, Xi; Sullam, Paul M.; Iverson, T. M.

2016-01-01

Streptococcus sanguinis is a leading cause of infective endocarditis, a life-threatening infection of the cardiovascular system. An important interaction in the pathogenesis of infective endocarditis is attachment of the organisms to host platelets. S. sanguinis expresses a serine-rich repeat adhesin, SrpA, similar in sequence to platelet-binding adhesins associated with increased virulence in this disease. In this study, we determined the first crystal structure of the putative binding region of SrpA (SrpABR) both unliganded and in complex with a synthetic disaccharide ligand at 1.8 and 2.0 Å resolution, respectively. We identified a conserved Thr-Arg motif that orients the sialic acid moiety and is required for binding to platelet monolayers. Furthermore, we propose that sequence insertions in closely related family members contribute to the modulation of structural and functional properties, including the quaternary structure, the tertiary structure, and the ligand-binding site. PMID:26833566

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.

Structural characteristics of alkaline phosphatase from the moderately halophilic bacterium Halomonas sp. 593

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

Arai, Shigeki; Yonezawa, Yasushi; Ishibashi, Matsujiro

2014-03-01

In order to clarify the structural basis of the halophilic characteristics of an alkaline phosphatase derived from the moderate halophile Halomonas sp. 593 (HaAP), the tertiary structure of HaAP was determined to 2.1 Å resolution by X-ray crystallography. The structural properties of surface negative charge and core hydrophobicity were shown to be intermediate between those characteristic of halophiles and non-halophiles, and may explain the unique functional adaptation to a wide range of salt concentrations. Alkaline phosphatase (AP) from the moderate halophilic bacterium Halomonas sp. 593 (HaAP) catalyzes the hydrolysis of phosphomonoesters over a wide salt-concentration range (1–4 M NaCl). Inmore » order to clarify the structural basis of its halophilic characteristics and its wide-range adaptation to salt concentration, the tertiary structure of HaAP was determined by X-ray crystallography to 2.1 Å resolution. The unit cell of HaAP contained one dimer unit corresponding to the biological unit. The monomer structure of HaAP contains a domain comprised of an 11-stranded β-sheet core with 19 surrounding α-helices similar to those of APs from other species, and a unique ‘crown’ domain containing an extended ‘arm’ structure that participates in formation of a hydrophobic cluster at the entrance to the substrate-binding site. The HaAP structure also displays a unique distribution of negatively charged residues and hydrophobic residues in comparison to other known AP structures. AP from Vibrio sp. G15-21 (VAP; a slight halophile) has the highest similarity in sequence (70.0% identity) and structure (C{sup α} r.m.s.d. of 0.82 Å for the monomer) to HaAP. The surface of the HaAP dimer is substantially more acidic than that of the VAP dimer (144 exposed Asp/Glu residues versus 114, respectively), and thus may enable the solubility of HaAP under high-salt conditions. Conversely, the monomer unit of HaAP formed a substantially larger hydrophobic interior comprising 329 C atoms from completely buried residues, whereas that of VAP comprised 264 C atoms, which may maintain the stability of HaAP under low-salt conditions. These characteristics of HaAP may be responsible for its unique functional adaptation permitting activity over a wide range of salt concentrations.« less

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.

DERMAL, ORAL AND INHALATION PHARMACOKINETICS OF METHYL TERTIARY-BUTYL ETHER (MTBE) IN HUMAN VOLUNTEERS

EPA Science Inventory

Methyl tertiary butyl ether (MTBE), a gasoline additive used to increase octane and reduce carbon monoxide emissions and ozone precursors, has contaminated drinking water and can lead to exposure by oral, inhalation, and dermal routes. To determine its dermal, oral, and inhal...

Geology and tectonic development of the continental margin north of Alaska

USGS Publications Warehouse

Grantz, A.; Eittreim, S.; Dinter, D.A.

1979-01-01

The continental margin north of Alaska, as interpreted from seismic reflection profiles, is of the Atlantic type and consists of three sectors of contrasting structure and stratigraphy. The Chukchi sector, on the west, is characterized by the deep late Mesozoic and Tertiary North Chukchi basin and the Chukchi Continental Borderland. The Barrow sector of central northern Alaska is characterized by the Barrow arch and a moderately thick continental terrace build of Albian to Tertiary clastic sediment. The terrace sedimentary prism is underlain by lower Paleozoic metasedimentary rocks. The Barter Island sector of northeastern Alaska and Yukon Territory is inferred to contain a very thick prism of Jurassic, Cretaceous and Tertiary marine and nonmarine clastic sediment. Its structure is dominated by a local deep Tertiary depocenter and two regional structural arches. We postulate that the distinguishing characteristics of the three sectors are inherited from the configuration of the rift that separated arctic Alaska from the Canadian Arctic Archipelago relative to old pre-rift highlands, which were clastic sediment sources. Where the rift lay relatively close to northern Alaska, in the Chukchi and Barter Island sectors, and locally separated Alaska from the old source terranes, thick late Mesozoic and Tertiary sedimentary prisms extend farther south beneath the continental shelf than in the intervening Barrow sector. The boundary between the Chukchi and Barrow sectors is relatively well defined by geophysical data, but the boundary between the Barrow and Barter Island sectors can only be inferred from the distribution and thickness of Jurassic and Cretaceous sedimentary rocks. These boundaries may be extensions of oceanic fracture zones related to the rifting that is postulated to have opened the Canada Basin, probably beginning during the Early Jurassic. ?? 1979.

Preliminary model of the pre-Tertiary basement rocks beneath Yucca Flat, Nevada Test Site, Nevada, based on analysis of gravity and magnetic data

USGS Publications Warehouse

Phelps, Geoffrey A.; McKee, Edwin H.; Sweetkind, D.; Langenheim, V.E.

2000-01-01

The Environmental Restoration Program of the U.S. Department of Energy, Nevada Operations Office, was developed to investigate the possible consequences to the environment of 40 years of nuclear testing on the Nevada Test Site. The majority of the tests were detonated underground, introducing contaminants into the ground-water system (Laczniak and others, 1996). An understanding of the ground-water flow paths is necessary to evaluate the extent of ground-water contamination. This report provides information specific to Yucca Flat on the Nevada Test Site. Critical to understanding the ground-water flow beneath Yucca Flat is an understanding of the subsurface geology, particularly the structure and distribution of the pre-Tertiary rocks, which comprise both the major regional aquifer and aquitard sequences (Winograd and Thordarson, 1975; Laczniak and others, 1996). Because the pre-Tertiary rocks are not exposed at the surface of Yucca Flat their distribution must be determined through well logs and less direct geophysical methods such as potential field studies. In previous studies (Phelps and others, 1999; Phelps and Mckee, 1999) developed a model of the basement surface of the Paleozoic rocks beneath Yucca Flat and a series of normal faults that create topographic relief on the basement surface. In this study the basement rocks and structure of Yucca Flat are examined in more detail using the basement gravity anomaly derived from the isostatic gravity inversion model of Phelps and others (1999) and high-resolution magnetic data, as part of an effort to gain a better understanding of the Paleozoic rocks beneath Yucca Flat in support of groundwater modeling.

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

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

Map showing structure contours on the top of the upper Jurassic Morrison Formation, Powder River basin, Wyoming and Montana

USGS Publications Warehouse

Crysdale, B.L.

1991-01-01

This map is one in a series of U.S. Geological Survey Miscellaneous Field Studies (MF) maps showing computer-generated structure contours, isopachs, and cross sections of selected formations in the Powder River basin, Wyoming and Montana. The map and cross sections were constructed from information stored in a U.S. Geological Survey Evolution of Sedimentary Basins data base. This data base contains picks of geologic formation and (or) unit tops and bases determined from electric resistivity and gamma-ray logs of 8,592 wells penetrating Tertiary and older rocks in the Powder River basin. Well completion cards (scout tickets) were reviewed and compared with copies of all logs, and formation or unit contacts determined by N. M. Denson, D.L. Macke, R. R. Schumann and others. This isopach map is based on information from 2,429 of these wells that penetrate the Minnelusa Formation and equivalents.

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.

Measuring case-mix complexity of tertiary care hospitals using DRGs.

PubMed

Park, Hayoung; Shin, Youngsoo

2004-02-01

The objectives of the study were to develop a model that measures and evaluates case-mix complexity of tertiary care hospitals, and to examine the characteristics of such a model. Physician panels defined three classes of case complexity and assigned disease categories represented by Adjacent Diagnosis Related Groups (ADRGs) to one of three case complexity classes. Three types of scores, indicating proportions of inpatients in each case complexity class standardized by the proportions at the national level, were defined to measure the case-mix complexity of a hospital. Discharge information for about 10% of inpatient episodes at 85 hospitals with bed size larger than 400 and their input structure and research and education activity were used to evaluate the case-mix complexity model. Results show its power to predict hospitals with the expected functions of tertiary care hospitals, i.e. resource intensive care, expensive input structure, and high levels of research and education activities.

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.

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.

Identification of linker regions and domain borders of the transcription activator protein NtrC from Escherichia coli by limited proteolysis, in-gel digestion, and mass spectrometry.

PubMed

Bantscheff, M; Weiss, V; Glocker, M O

1999-08-24

We have developed a mass spectrometry based method for the identification of linker regions and domain borders in multidomain proteins. This approach combines limited proteolysis and in-gel proteolytic digestions and was applied to the determination of linkers in the transcription factor NtrC from Escherichia coli. Limited proteolysis of NtrC with thermolysin and papain revealed that initial digestion yielded two major bands in SDS-PAGE that were identified by mass spectrometry as the R-domain and the still covalently linked OC-domains. Subsequent steps in limited proteolysis afforded further cleavage of the OC-fragment into the O- and the C-domain at accessible amino acid residues. Mass spectrometric identification of the tryptic/thermolytic peptides obtained after in-gel total proteolysis of the SDS-PAGE-separated domains determined the domain borders and showed that the protease accessible linker between R- and O-domain comprised amino acids Val-131 and Gln-132 within the "Q-linker" in agreement with papain and subtilisin digestion. The region between amino acid residues Thr-389 and Gln-396 marked the hitherto unknown linker sequence that connects the O- with the C-domain. High abundances of proline-, alanine-, serine-, and glutamic acid residues were found in this linker structure (PASE-linker) of related NtrC response regulator proteins. While R- and C-domains remained stable under the applied limited proteolysis conditions, the O-domain was further truncated yielding a core fragment that comprised the sequence from Ile-140 to Arg-320. ATPase activity was lost after separation of the R-domain from the OC-fragment. However, binding of OC- and C- fragments to specific DNA was observed by characteristic band-shifts in migration retardation assays, indicating intact tertiary structures of the C-domain. The outlined strategy proved to be highly efficient and afforded lead information of tertiary structural features necessary for protein design and engineering and for structure-function studies.

Determination of tertiary amines and salts of organic acids in acetic acid by catalytic thermometric titration.

PubMed

Vajgand, V J; Gaál, F F

1967-03-01

A new method of determination of tertiary amines and salts of organic adds in acetic acid solution, to which about 2 % of water and 8% acetic anhydride are added, is described. After the equivalence point, the excess of perchloric acid catalyses the exothermic reaction of water with acetic anhydride. The end-point is determined from the graph of temperature against volume of added titrant. If a slightly soluble compound is produced during the titration, the precision of the new method is superior to that of the potentiometric method.

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…

Separating the Spectral Components of the Massive Triple Star System Delta Orionis

NASA Astrophysics Data System (ADS)

Gies, Douglas

2013-10-01

The multiple star system of delta Orionis represents one of the closest examples of a luminous O-star with a strong stellar wind, and it was the target of a recent multi-wavelength campaign to determine the source of the wind X-ray emission. It consists of aclose eclipsing binary with a more distant tertiary, and all the components are massive stars. Investigations of the radial velocity curves of the eclipsing system are made difficult by severe line blending with the spectral lines of the tertiary star, and the resulting mass estimates range by a factor of two. We propose that the solution to this problem is to isolate the flux of the tertiary through high angular resolutionspectroscopy with HST/STIS, and we show how a two visit program of ultraviolet and spatially resolved spectroscopy will provide us with the means to characterize the spectra of all three stars in the triple. This will allow us to reassess a large body of existing optical and UV spectroscopy and determine reliable radial velocity curves for the components in the close binary. By then fitting a new high precision light curve from MOST photometry, we will derive accurate masses, temperatures, radii, and projected rotational velocities for all the components. The inner binary also hasa measured apsidal period, and the new results will form a key test of models of interior structure. The analysis will also provide secure estimates for the geometry and size of the inner binary and the radius of the secondary, the parameters required to analyze the orbital phase variations and sites of origin of the wind X-ray emission documented in a recent Chandra/HETGS program.

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

Implosion symmetry and ρR measurements on the National Ignition Facility from nascent 27-31 MeV tertiary protons (invited) (abstract)

NASA Astrophysics Data System (ADS)

Petrasso, Richard D.

1997-01-01

Tertiary protons with birth energies from ˜27 to 30.8 MeV result from the implosion of ignition-scale inertial confinement fusion targets, such as those planned for the National Ignition Facility (NIF). Measurement of the tertiaries' slowing can provide a determination of the imploded areal density of the fuel capsule, as well as implosion asymmetry that results from anisotropy of the areal density and plasma temperature. In order to determine the utility of tertiaries for all phases of the NIF, we analyze three representative cases: a gas capsule (0.7 kJ yield); a cryogenic fuel capsule that fails to ignite (15 kJ); and a cryogenic fuel capsule that ignites and burns (13 000 kJ). In each case, tertiaries escape from the capsule and convey critical information about implosion dynamics. In addition, we show that for some gas-capsule implosions anticipated on OMEGA, tertiaries may be the only species of energetic charged particles that can determine the fuel areal density. Presently, we are building a charge-coupled device (CCD)-based charged particle spectrometer for OMEGA and for NOVA. In addition to the tertiaries, the spectrometers are sensitive to a variety of the energetic charged particles, such as knock-on protons, deuterons, and tritons, and 3He-burnup protons. In fact the latter set of charged particles will usually be the dominant signal. We will describe the basic features of the spectrometers and the measured response of the CCDs to 1-5 MeV protons, 1-5 MeV alphas, and 14 MeV neutrons (and associated gammas), the latter constitute the principal source of noise. This work is done in collaboration with C. K. Li, D. Hicks, and F. Seguin of MIT; with B. Burke of LL/MIT; with M. Cable, S. Pollaine, S. Haan, T. Bernat, T. Phillips, and J. Kilkenny of LLNL; with J, Knauer, S. Cremer, C. Verdon, and B. Kremens of University of Rochester; and with C. Ruiz and R. Leeper of SNL. This work is supported in part by LLNL Subcontract B313875 and University of Rochester Subcontract 410025-G.

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

BLUE RANGE WILDERNESS, ARIZONA AND NEW MEXICO.

USGS Publications Warehouse

Ratte, James C.; Raabe, R.G.

1984-01-01

A mineral survey of the area was completed and it was determined that a probable resource potential for molybdenum, copper, and silver is present in volcanic rocks of middle Tertiary age in the southern and southwestern parts of the area. There is also a likelihood for the occurrence of base-metal resources (including porphyry copper deposits) of Laramide age beneath the middle Tertiary volcanic rocks that cover the area, but data are insufficient to assess the resource potential. Improved techniques for interpreting geophysical data collected over complex volcanic terranes should be applied in an effort to identify Laramide intrusives beneath the middle Tertiary rocks. Additional geologic studies of the major faults and volcanic centers might enhance mineral-deposit target definition in the middle Tertiary rocks.

Isotopic and anatomical evidence of an herbivorous diet in the Early Tertiary giant bird Gastornis. Implications for the structure of Paleocene terrestrial ecosystems

NASA Astrophysics Data System (ADS)

Angst, D.; Lécuyer, C.; Amiot, R.; Buffetaut, E.; Fourel, F.; Martineau, F.; Legendre, S.; Abourachid, A.; Herrel, A.

2014-04-01

The mode of life of the early Tertiary giant bird Gastornis has long been a matter of controversy. Although it has often been reconstructed as an apex predator feeding on small mammals, according to other interpretations, it was in fact a large herbivore. To determine the diet of this bird, we analyze here the carbon isotope composition of the bone apatite from Gastornis and contemporaneous herbivorous mammals. Based on 13C-enrichment measured between carbonate and diet of carnivorous and herbivorous modern birds, the carbonate δ13C values of Gastornis bone remains, recovered from four Paleocene and Eocene French localities, indicate that this bird fed on plants. This is confirmed by a morphofunctional study showing that the reconstructed jaw musculature of Gastornis was similar to that of living herbivorous birds and unlike that of carnivorous forms. The herbivorous Gastornis was the largest terrestrial tetrapod in the Paleocene biota of Europe, unlike the situation in North America and Asia, where Gastornis is first recorded in the early Eocene, and the largest Paleocene animals were herbivorous mammals. The structure of the Paleocene terrestrial ecosystems of Europe may have been similar to that of some large islands, notably Madagascar, prior to the arrival of humans.

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

Factors Influencing Institutional-Based Pediatric Rehabilitation Services among Caregivers of Children with Developmental Delay in Southwestern Rajasthan.

PubMed

Mishra, Kriti; Siddharth, V

2018-01-01

A limited number of caregivers of children with developmental delay access rehabilitation facilities in India. The study explored utilization of rehabilitation services at a tertiary care setup in southwestern Rajasthan and various factors influencing it. The aim of this study is to explore rehabilitation service utilization among children with developmental delay at a tertiary care setup and to ascertain factors that influence this pattern. This study was conducted at the department of physical medicine and rehabilitation at tertiary care setup. This was an observational study. Children with developmental delay who were advised institutional-based rehabilitation were identified over span of 1 year. Those who failed to return for rehabilitation after the first visit were interviewed telephonically. The interview had semi-structured open-ended questions about their reasons for inability to avail services. SPSS statistics 22 was used for descriptive analysis and correlation of variables. Of 230 children with developmental delay visiting department in 1-year duration, 48 took regular rehabilitation. Parents of 129 children with complete records were asked regarding discontinuation. Factors cited by majority were long distance from institute and service at hospital. Other reasons for discontinuation were related to belief system, family issues, time issues, socioeconomic factors, etc. Socioeconomic status was significantly associated with parental education (C = 0.488, P = 0.000) and financial issues. Location of family had significant association with long distance (C = 0.315, P = 0.000), parental education (C = 0.251, P = 0.003), and belief system (C = 0.265, P = 0.002). Distance from institute and quality of hospital service determined rehabilitation service use at a tertiary institute. Other factors such as socioeconomic status, family support, and social belief system must also be addressed while delivering institutional rehabilitation to children.

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

Self-Assessment in Professional Programmes within Tertiary Institutions

ERIC Educational Resources Information Center

Bourke, Roseanna

2014-01-01

Self-assessment at tertiary level is a critical pedagogical and assessment tool to support students in their transition to professional careers where on-going learning and assessment is required. Beyond the safety-net of course content, external assessment and pre-determined criteria, novice professionals need to find ways to self-assess their…

A Framework for Enabling Graduate Outcomes in Undergraduate Programmes

ERIC Educational Resources Information Center

Bond, C. H.; Spronken-Smith, R.; McLean, A.; Smith, N.; Frielick, S.; Jenkins, M.; Marshall, S.

2017-01-01

Our research aim was to determine what enables engagement with graduate outcomes in tertiary institutions in Aotearoa/New Zealand. We used a mixed methods approach comprising a survey sent to all tertiary institutions, follow-up interviews with 10 academic leaders and eight case studies of good practice of programmes engaged with graduate outcomes…

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.

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

Investigation on the pH-dependent binding of benzocaine and lysozyme by fluorescence and absorbance.

PubMed

Li, Shihui; Li, Daojin

2011-11-01

The interaction mechanism between benzocaine (BZC) and lysozyme (Lys) has been investigated by fluorescence, synchronous fluorescence, ultraviolet-vis (UV) absorption spectra, and three-dimensional fluorescence (3-D) in various pH medium. The observations of fluorescence spectra were mainly rationalized in terms of a static quenching process at lower concentration of BZC (C(BZC)/C(Lys)<9) and a combined quenching process at higher concentration of BZC (C(BZC)/C(Lys)>9) at pH 7.4 and 8.4. However, the fluorescence quenching was mainly arisen from static quenching by complex formation in all studied drug concentrations at pH 3.5. The structural characteristics of BZC and Lys were probed, and their binding affinities were determined under different pH conditions (pH 3.5, 7.4, and 8.4). The results indicated that the binding abilities of BZC to Lys decreased at the pH below and above the simulative physiological condition (pH 7.4) due to the alterations of the protein secondary and tertiary structures or the structural change of BZC. The effect of BZC on the conformation of Lys was analyzed using UV, synchronous fluorescence and three-dimensional fluorescence under different pH conditions. These results indicate that the binding of BZC to Lys causes apparent change in the secondary and tertiary structures of Lys. The effect of Zn(2+) on the binding constant of BZC with Lys under various pH conditions (pH 3.5, 7.4, and 8.4) was also studied. Copyright © 2011 Elsevier B.V. All rights reserved.

Formation Mechanism of NDMA from Ranitidine, Trimethylamine, and Other Tertiary Amines during Chloramination: A Computational Study

PubMed Central

2015-01-01

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. PMID:24968236

Physician job satisfaction in Saudi Arabia: insights from a tertiary hospital survey.

PubMed

Aldrees, Turki; Al-Eissa, Sami; Badri, Motasim; Aljuhayman, Ahmed; Zamakhshary, Mohammed

2015-01-01

Job satisfaction refers to the extent to which people like or dislike their job. Job satisfaction varies across professions. Few studies have explored this issue among physicians in Saudi Arabia. The objective of this study is to determine the level and factors associated with job satisfaction among Saudi and non-Saudi physicians. In this cross-sectional study conducted in a major tertiary hospital in Riyadh, a 5-point Likert scale structured questionnaire was used to collect data on a wide range of socio-demographic, practice environment characteristics and level and consequences of job satisfaction from practicing physicians (consultants or residents) across different medical specialties. Logistic regression models were fitted to determine factors associated with job satisfaction. Of 344 participants, 300 (87.2%) were Saudis, 252 (73%) males, 255 (74%) married, 188 (54.7%) consultants and age [median (IQR)] was 32 (27-42.7) years. Overall, 104 (30%) respondents were dissatisfied with their jobs. Intensive care physicians were the most dissatisfied physicians (50%). In a multiple logistic regression model, income satisfaction (odds ratio [OR]=0.448 95% CI 0.278-0.723, P < .001) was the only factor independently associated with dissatisfaction. Factors adversely associated with physicians job satisfaction identified in this study should be addressed in governmental strategic planning aimed at improving the healthcare system and patient care.

An RNA internal loop acts as a hinge to facilitate ribozyme folding and catalysis.

PubMed Central

Szewczak, A A; Cech, T R

1997-01-01

RNA molecules commonly consist of helical regions separated by internal loops, and in many cases these internal loops have been found to assume stable structures. We have examined the function and dynamics of an internal loop, J5/5a, that joins the two halves of the P4-P6 domain of the Tetrahymena self-splicing group I intron. P4-P6 RNAs with mutations in the J5/5a region showed nondenaturing gel electrophoretic mobilities and levels of Fe(II)-EDTA cleavage protection intermediate between those of wild-type RNA and a mutant incapable of folding into the native P4-P6 tertiary structure. Mutants with the least structured J5/5a loops behaved the most like wild-type P4-P6, and required smaller amounts of Mg2+ to rescue folding. The activity of reconstituted introns containing mutant P4-P6 RNAs correlated similarly with the nature of the J5/5a mutation. Our results suggest that, in solution, the P4-P6 RNA is in a two-state equilibrium between folded and unfolded states. We conclude that this internal loop mainly acts as a flexible hinge, allowing the coaxially stacked helical regions on either side of it to interact via specific tertiary contacts. To a lesser extent, the specific bases within the loop contribute to folding. Furthermore, it is crucial that the junction remain unstructured in the unfolded state. These conclusions cannot be derived from a simple examination of the P4-P6 crystal structure (Cate JH et al., 1996, Science 273:1678-1685), showing once again that structure determination must be supplemented with mutational and thermodynamic analysis to provide a complete picture of a folded macromolecule. PMID:9257643

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.

Asymmetric structure of five and six membered DNA hairpin loops

NASA Technical Reports Server (NTRS)

Baumann, U.; Chang, S.

1995-01-01

The tertiary structure of nucleic acid hairpins was elucidated by means of the accessibility of the single-strand-specific nuclease from mung bean. This molecular probe has proven especially useful in determining details of the structural arrangement of the nucleotides within a loop. In this study 3'-labeling is introduced to complement previously used 5'-labeling in order to assess and to exclude possible artifacts of the method. Both labeling procedures result in mutually consistent cleavage patterns. Therefore, methodological artifacts can be excluded and the potential of the nuclease as structural probe is increased. DNA hairpins with five and six membered loops reveal an asymmetric loop structure with a sharp bend of the phosphate-ribose backbone between the second and third nucleotide on the 3'-side of a loop. These hairpin structures differ from smaller loops with 3 or 4 members, which reveal this type of bend between the first and second 3' nucleotide, and resemble with respect to the asymmetry anticodon loops of tRNA.

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

One-microsecond molecular dynamics simulation of channel gating in a nicotinic receptor homologue

PubMed Central

Nury, Hugues; Poitevin, Frédéric; Van Renterghem, Catherine; Changeux, Jean-Pierre; Corringer, Pierre-Jean; Delarue, Marc; Baaden, Marc

2010-01-01

Recently discovered bacterial homologues of eukaryotic pentameric ligand-gated ion channels, such as the Gloeobacter violaceus receptor (GLIC), are increasingly used as structural and functional models of signal transduction in the nervous system. Here we present a one-microsecond-long molecular dynamics simulation of the GLIC channel pH stimulated gating mechanism. The crystal structure of GLIC obtained at acidic pH in an open-channel form is equilibrated in a membrane environment and then instantly set to neutral pH. The simulation shows a channel closure that rapidly takes place at the level of the hydrophobic furrow and a progressively increasing quaternary twist. Two major events are captured during the simulation. They are initiated by local but large fluctuations in the pore, taking place at the top of the M2 helix, followed by a global tertiary relaxation. The two-step transition of the first subunit starts within the first 50 ns of the simulation and is followed at 450 ns by its immediate neighbor in the pentamer, which proceeds with a similar scenario. This observation suggests a possible two-step domino-like tertiary mechanism that takes place between adjacent subunits. In addition, the dynamical properties of GLIC described here offer an interpretation of the paradoxical properties of a permeable A13′F mutant whose crystal structure determined at 3.15 Å shows a pore too narrow to conduct ions. PMID:20308576

Chemical glycosylation of cytochrome c improves physical and chemical protein stability.

PubMed

Delgado, Yamixa; Morales-Cruz, Moraima; Hernández-Román, José; Martínez, Yashira; Griebenow, Kai

2014-08-06

Cytochrome c (Cyt c) is an apoptosis-initiating protein when released into the cytoplasm of eukaryotic cells and therefore a possible cancer drug candidate. Although proteins have been increasingly important as pharmaceutical agents, their chemical and physical instability during production, storage, and delivery remains a problem. Chemical glycosylation has been devised as a method to increase protein stability and thus enhance their long-lasting bioavailability. Three different molecular weight glycans (lactose and two dextrans with 1 kD and 10 kD) were chemically coupled to surface exposed Cyt c lysine (Lys) residues using succinimidyl chemistry via amide bonds. Five neo-glycoconjugates were synthesized, Lac4-Cyt-c, Lac9-Cyt-c, Dex5(10kD)-Cyt-c, Dex8(10kD)-Cyt-c, and Dex3(1kD)-Cyt-c. Subsequently, we investigated glycoconjugate structure, activity, and stability. Circular dichroism (CD) spectra demonstrated that Cyt c glycosylation did not cause significant changes to the secondary structure, while high glycosylation levels caused some minor tertiary structure perturbations. Functionality of the Cyt c glycoconjugates was determined by performing cell-free caspase 3 and caspase 9 induction assays and by measuring the peroxidase-like pseudo enzyme activity. The glycoconjugates showed ≥94% residual enzyme activity and 86 ± 3 to 95 ± 1% relative caspase 3 activation compared to non-modified Cyt c. Caspase 9 activation by the glycoconjugates was with 92 ± 7% to 96 ± 4% within the error the same as the caspase 3 activation. There were no major changes in Cyt c activity upon glycosylation. Incubation of Dex3(1 kD)-Cyt c with mercaptoethanol caused significant loss in the tertiary structure and a drop in caspase 3 and 9 activation to only 24 ± 8% and 26 ± 6%, respectively. This demonstrates that tertiary structure intactness of Cyt c was essential for apoptosis induction. Furthermore, glycosylation protected Cyt c from detrimental effects by some stresses (i.e., elevated temperature and humidity) and from proteolytic degradation. In addition, non-modified Cyt c was more susceptible to denaturation by a water-organic solvent interface than its glycoconjugates, important for the formulation in polymers. The results demonstrate that chemical glycosylation is a potentially valuable method to increase Cyt c stability during formulation and storage and potentially during its application after administration.

Abusive Head Trauma at a Tertiary Care Children's Hospital in Mexico City. A Preliminary Study

ERIC Educational Resources Information Center

Diaz-Olavarrieta, Claudia; Garcia-Pina, Corina A.; Loredo-Abdala, Arturo; Paz, Francisco; Garcia, Sandra G.; Schilmann, Astrid

2011-01-01

Objectives: Determine the prevalence, clinical signs and symptoms, and demographic and family characteristics of children attending a tertiary care hospital in Mexico City, Mexico, to illustrate the characteristics of abusive head trauma among this population. Methods: This is a cross-sectional descriptive study of infants and children under 5,…

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.

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.

Protein folding: understanding the role of water and the low Reynolds number environment as the peptide chain emerges from the ribosome and folds.

PubMed

Sen, Siddhartha; Voorheis, H Paul

2014-12-21

The mechanism of protein folding during early stages of the process has three determinants. First, moving water molecules obey the rules of low Reynolds number physics without an inertial component. Molecular movement is instantaneous and size insensitive. Proteins emerging from the ribosome move and rotate without an external force if they change shape, forming and propagating helical structures that increases translocational efficiency. Forward motion ceases when the shape change or propelling force ceases. Second, application of quantum field theory to water structure predicts the spontaneous formation of low density coherent units of fixed size that expel dissolved atmospheric gases. Structured water layers with both coherent and non-coherent domains, form a sheath around the new protein. The surface of exposed hydrophobic amino acids is protected from water contact by small nanobubbles of dissolved atmospheric gases, 5 or 6 molecules on average, that vibrate, attracting even widely separated resonating nanobubbles. This force results from quantum effects, appearing only when the system is within and interacts with an oscillating electromagnetic field. The newly recognized quantum force sharply bends the peptide and is part of a dynamic field determining the pathway of protein folding. Third, the force initiating the tertiary folding of proteins arises from twists at the position of each hydrophobic amino acid, that minimizes surface exposure of the hydrophobic amino acids and propagates along the protein. When the total bend reaches 360°, the leading segment of water sheath intersects the trailing segment. This steric self-intersection expels water from overlapping segments of the sheath and by Newton׳s second law moves the polypeptide chain in an opposite direction. Consequently, with very few exceptions that we enumerate and discuss, tertiary structures are absent from proteins without hydrophobic amino acids, which control the early stages of protein folding and the overall shape of protein. Consequently, proteins only adopt a limited number of forms. The formation of quaternary structures is not necessarily prevented by the absence of hydrophobic amino acids. Copyright © 2014 Elsevier Ltd. All rights reserved.

Women and physics education in Trinidad and Tobago

NASA Astrophysics Data System (ADS)

Watts, Shelly C.; Daley, Candice

2013-03-01

The following paper focuses on the education system in Trinidad and Tobago, particularly on the involvement of girls and women in physics. The educational system is a three-tiered structure: primary, secondary, and tertiary levels. Girls and women are given equal opportunities at all levels; however, career choices and the demand of the job market determines whether physics is chosen at the secondary level and onward. No formal survey was performed to quantify the number of girls and women involved in physics; however, scenarios are used to illustrate the different opportunities and tracks that are available to girls.

Ground-water resources of Sheridan County, Wyoming

USGS Publications Warehouse

Lowry, Marlin E.; Cummings, T. Ray

1966-01-01

Sheridan County is in the north-central part of Wyoming and is an area of about 2,500 square miles. The western part of the county is in the Bighorn Mountains, and the eastern part is in the Powder River structural basin. Principal streams are the Powder and Tongue Rivers, which are part of the Yellowstone River system. The climate is semiarid, and the mean annual precipitation at Sheridan is about 16 inches. Rocks of Precambrian age are exposed in the central part of the Bighorn Mountains, and successively younger rocks are exposed eastward. Rocks of Tertiary age, which are the most widespread, are exposed throughout a large part of the Powder River structural basin. Deposits of Quaternary age underlie the flood plains and terraces along the larger streams, particularly in the western part of the basin. Aquifers of pre-Tertiary age are exposed in the western part of the county, but they dip steeply and are deeply buried just a few miles east of their outcrop. Aquifers that might yield large supplies of water include the Bighorn Dolomite, Madison Limestone, Amsden Formation, and Tensleep Sandstone. The Flathead Sandstone, Sundance Formation, Morrison Formation, Cloverly Formation,. Newcastle Sandstone, Frontier Formation, Parkman Sandstone, Bearpaw Shale, .and Lance Formation may yield small or, under favorable conditions, moderate supplies of water. Few wells tap aquifers of pre-Tertiary age, and these are restricted to the outcrop area. The meager data available indicate that the water from the Lance Formation, Bearpaw Shale, Parkman Sandstone, Tensleep Sandstone and Amsden Formation, and Flathead Standstone is of suitable quality for domestic or stock purposes, and that water from the Tensleep Sandstone and Amsden Formation and the Flathead Sandstone is of good quality for irrigation. Samples could not be obtained from other aquifers of pre-Tertiary age; so the quality of water in these aquifers could not be determined. Adequate supplies of ground water for stock or domestic use can be developed throughout much of the report area from the Fort Union and Wasatch Formations of Tertiary age; larger supplies might be obtained from the coarse-grained sandstone facies of the Wasatch Formation near Moncreiffe Ridge. Four aquifer tests were made at wells tapping formations of Tertiary age, and the coefficients of permeability determined ranged from 2.5 to 7.9 gallons per day per square foot. The depths to which wells must be drilled to penetrate an aquifer differ within relatively short distances because of the lenticularity of the aquifers. Water in aquifers of Tertiary age may occur under water-table, artesian, or a combination of artesian and gas-lift conditions. Water from the Fort Union is usable for domestic purposes, but the iron and dissolved-solids content impair the quality at some localities. Water from the Fort Union Formation is not recommended for irrigation because of sodium and bicarbonate content. The water is regarded as good to fair for stock use. Water from the Wasatch Formation generally contains dissolved solids in excess of the suggested domestic standards, but this water is usable in the absence of other supplies. The development of irrigation supplies from the Wasatch Formation may be possible in some areas, but the water quality should be carefully checked. Water of good to very poor quality for stock supplies is obtained, depending upon the location. Hydrogen sulfide, commonly present in water of the Fort Union and Wasatch Formations, becomes an objectionable characteristic when the water is used for human consumption. Deposits of Quaternary age generally yield small to moderate supplies of water to wells. Two pumping tests were conducted, and the coefficients of permeability of the aquifers tested were 380 and 1,100 gallons per day per square foot. Usable supplies of ground water can be developed from the deposits of Quaternary age, principally along the valleys of perennial strea

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

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.

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.

Exploring GPCR-Lipid Interactions by Molecular Dynamics Simulations: Excitements, Challenges, and the Way Forward.

PubMed

Sengupta, Durba; Prasanna, Xavier; Mohole, Madhura; Chattopadhyay, Amitabha

2018-06-07

Gprotein-coupled receptors (GPCRs) are seven transmembrane receptors that mediate a large number of cellular responses and are important drug targets. One of the current challenges in GPCR biology is to analyze the molecular signatures of receptor-lipid interactions and their subsequent effects on GPCR structure, organization, and function. Molecular dynamics simulation studies have been successful in predicting molecular determinants of receptor-lipid interactions. In particular, predicted cholesterol interaction sites appear to correspond well with experimentally determined binding sites and estimated time scales of association. In spite of several success stories, the methodologies in molecular dynamics simulations are still emerging. In this Feature Article, we provide a comprehensive overview of coarse-grain and atomistic molecular dynamics simulations of GPCR-lipid interaction in the context of experimental observations. In addition, we discuss the effect of secondary and tertiary structural constraints in coarse-grain simulations in the context of functional dynamics and structural plasticity of GPCRs. We envision that this comprehensive overview will help resolve differences in computational studies and provide a way forward.

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.

Riboswitches: emerging themes in RNA structure and function.

PubMed

Montange, Rebecca K; Batey, Robert T

2008-01-01

Riboswitches are RNAs capable of binding cellular metabolites using a diverse array of secondary and tertiary structures to modulate gene expression. The recent determination of the three-dimensional structures of parts of six different riboswitches illuminates common features that allow riboswitches to be grouped into one of two types. Type I riboswitches, as exemplified by the purine riboswitch, are characterized by a single, localized binding pocket supported by a largely pre-established global fold. This arrangement limits ligand-induced conformational changes in the RNA to a small region. In contrast, Type II riboswitches, such as the thiamine pyrophosphate riboswitch, contain binding pockets split into at least two spatially distinct sites. As a result, binding induces both local changes to the binding pocket and global architecture. Similar organizational themes are found in other noncoding RNAs, making it possible to begin to build a hierarchical classification of RNA structure based on the spatial organization of their active sites and associated secondary structural elements.

Crystal structures of the components of the Staphylococcus aureus leukotoxin ED

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

Nocadello, S.; Minasov, G.; Shuvalova, L.

Staphylococcal leukotoxins are a family of β-barrel, bicomponent, pore-forming toxins with membrane-damaging functions. These bacterial exotoxins share sequence and structural homology and target several host-cell types. Leukotoxin ED (LukED) is one of these bicomponent pore-forming toxins thatStaphylococcus aureusproduces in order to suppress the ability of the host to contain the infection. The recent delineation of the important role that LukED plays inS. aureuspathogenesis and the identification of its protein receptors, combined with its presence inS. aureusmethicillin-resistant epidemic strains, establish this leukocidin as a possible target for the development of novel therapeutics. Here, the crystal structures of the water-soluble LukE andmore » LukD components of LukED have been determined. Lastly, the two structures illustrate the tertiary-structural variability with respect to the other leukotoxins while retaining the conservation of the residues involved in the interaction of the protomers in the bipartite leukotoxin in the pore complex.« less

Crystal structures of the components of the Staphylococcus aureus leukotoxin ED

DOE PAGES

Nocadello, S.; Minasov, G.; Shuvalova, L.; ...

2016-01-01

Staphylococcal leukotoxins are a family of β-barrel, bicomponent, pore-forming toxins with membrane-damaging functions. These bacterial exotoxins share sequence and structural homology and target several host-cell types. Leukotoxin ED (LukED) is one of these bicomponent pore-forming toxins thatStaphylococcus aureusproduces in order to suppress the ability of the host to contain the infection. The recent delineation of the important role that LukED plays inS. aureuspathogenesis and the identification of its protein receptors, combined with its presence inS. aureusmethicillin-resistant epidemic strains, establish this leukocidin as a possible target for the development of novel therapeutics. Here, the crystal structures of the water-soluble LukE andmore » LukD components of LukED have been determined. Lastly, the two structures illustrate the tertiary-structural variability with respect to the other leukotoxins while retaining the conservation of the residues involved in the interaction of the protomers in the bipartite leukotoxin in the pore complex.« less

Structural Basis for Sialoglycan Binding by the Streptococcus sanguinis SrpA Adhesin.

PubMed

Bensing, Barbara A; Loukachevitch, Lioudmila V; McCulloch, Kathryn M; Yu, Hai; Vann, Kendra R; Wawrzak, Zdzislaw; Anderson, Spencer; Chen, Xi; Sullam, Paul M; Iverson, T M

2016-04-01

Streptococcus sanguinisis a leading cause of infective endocarditis, a life-threatening infection of the cardiovascular system. An important interaction in the pathogenesis of infective endocarditis is attachment of the organisms to host platelets.S. sanguinisexpresses a serine-rich repeat adhesin, SrpA, similar in sequence to platelet-binding adhesins associated with increased virulence in this disease. In this study, we determined the first crystal structure of the putative binding region of SrpA (SrpABR) both unliganded and in complex with a synthetic disaccharide ligand at 1.8 and 2.0 Å resolution, respectively. We identified a conserved Thr-Arg motif that orients the sialic acid moiety and is required for binding to platelet monolayers. Furthermore, we propose that sequence insertions in closely related family members contribute to the modulation of structural and functional properties, including the quaternary structure, the tertiary structure, and the ligand-binding site. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Politics of Leadership and Implementation of Educational Policies and Programmes of Tertiary Institutions in Cross River State, Nigeria

ERIC Educational Resources Information Center

Ekpiken, W. E.; Ifere, Francis O.

2015-01-01

This paper examines issues of politics of leadership and implementation of Educational policies and programmes of tertiary institutions in Cross River State with a view to determine the problems are situated and suggest the way forward. It examines the concept of politics of education, concept of leadership, meaning of planning and generation of…

Ghostwriters Guaranteeing Grades? The Quality of Online Ghostwriting Services Available to Tertiary Students in Australia

ERIC Educational Resources Information Center

Lines, Lisa

2016-01-01

Ghostwriting is difficult to detect, it has the potential to be high quality, and universities do not currently have adequate policies in place to police it. Determining the quality of the ghostwriting services available to tertiary students is of vital importance because underestimating the potential for students to use these services to pass…

"Digitize Me": Generating E-Learning Profiles for Media and Communication Students in a Jamaican Tertiary-Level Institution

ERIC Educational Resources Information Center

Stewart-McKoy, Michelle A.

2014-01-01

The purpose of this project was to develop an e-learning profile for a group of media and communication students enrolled in a Jamaican tertiary-level institution in order to make informed decisions most the appropriate [online] learning complement for these students. The objectives sought to determine the e-learning profile of media and…

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.

Microanalysis (micro-XRF, micro-XANES, and micro-XRD) of a tertiary sediment using microfocused synchrotron radiation.

PubMed

Denecke, Melissa A; Somogyi, Andrea; Janssens, Koen; Simon, Rolf; Dardenne, Kathy; Noseck, Ulrich

2007-06-01

Micro-focused synchrotron radiation techniques to investigate actinide elements in geological samples are becoming an increasingly used tool in nuclear waste disposal research. In this article, results using mu-focus techniques are presented from a bore core section of a U-rich tertiary sediment collected from Ruprechtov, Czech Republic, a natural analog to nuclear waste repository scenarios in deep geological formations. Different methods are applied to obtain various, complementary information. Elemental and element chemical state distributions are obtained from micro-XRF measurements, oxidation states of As determined from micro-XANES, and the crystalline structure of selected regions are studied by means of micro-XRD. We find that preparation of the thin section created an As oxidation state artifact; it apparently changed the As valence in some regions of the sample. Results support our previously proposed hypothesis of the mechanism for U-enrichment in the sediment. AsFeS coating on framboid Fe nodules in the sediment reduced mobile groundwater-dissolved U(VI) to less-soluble U(IV), thereby immobilizing the uranium in the sediment.

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.

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.

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.

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.

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.

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.

New insights into the fundamental role of topological constraints as a determinant of two-way junction conformation

PubMed Central

Mustoe, Anthony M.; Bailor, Maximillian H.; Teixeira, Robert M.; Brooks, Charles L.; Al-Hashimi, Hashim M.

2012-01-01

Recent studies have shown that topological constraints encoded at the RNA secondary structure level involving basic steric and stereochemical forces can significantly restrict the orientations sampled by helices across two-way RNA junctions. Here, we formulate these topological constraints in greater quantitative detail and use this topological framework to rationalize long-standing but poorly understood observations regarding the basic behavior of RNA two-way junctions. Notably, we show that the asymmetric nature of the A-form helix and the finite length of a bulge provide a physical basis for the experimentally observed directionality and bulge-length amplitude dependence of bulge induced inter-helical bends. We also find that the topologically allowed space can be modulated by variations in sequence, particularly with the addition of non-canonical GU base pairs at the junction, and, surprisingly, by the length of the 5′ and 3′ helices. A survey of two-way RNA junctions in the protein data bank confirms that junction residues have a strong preference to adopt looped-in, non-canonically base-paired conformations, providing a route for extending our bulge-directed framework to internal loop motifs and implying a simplified link between secondary and tertiary structure. Finally, our results uncover a new simple mechanism for coupling junction-induced topological constraints with tertiary interactions. PMID:21937512

Social media use profile, social skills, and nurse-patient interaction among Registered Nurses in tertiary hospitals: A structural equation model analysis.

PubMed

Mariano, Micah Celine O; Maniego, John Christian M; Manila, Hariette Lou Marie D; Mapanoo, Ram Cedrick C; Maquiran, Kerwin Miguel A; Macindo, John Rey B; Tejero, Lourdes Marie S; Torres, Gian Carlo S

2018-04-01

Social media has become increasingly important over the past decades and has been integrated in various environments, including the healthcare setting. Yet, the influence of social media use on the social skills and nurse-patient interaction of nurses is an area in nursing that requires further studies. This study determined the interrelationships among social media use profile, social skills, and nurse-patient interaction of Registered Nurses in tertiary hospitals. Employing structural equation modeling, a descriptive-correlational study was conducted among 212 consecutively-selected nurses from two tertiary hospitals. Consenting respondents completed a two-part survey composed of the respondent profile sheet and the Social Skills Inventory. The respondent profile sheet assessed demographic profile and social media use profile in terms of the mode, frequency, and duration of utilization. Three trained team members observed each nurse-patient dyad and completed the Nurse-Patient Bonding Instrument. A good fit model illustrated the negative effects of frequent social media use to patient openness (β = -0.18, p < 0.05) and engagement (β = -0.11, p ≤ 0.05). Longer use of social media on a daily basis, however, positively affected both dimensions of social skills. Accessing social media platforms using non-handheld devices showed the most influential positive effects to social skills and nurse-patient interaction. Additionally, although verbal social skills positively affected most dimensions of nurse-patient interaction, non-verbal social skills negatively influenced patient engagement (β = -0.19, p = 0.019) and nurse openness (β = -0.38, p ≤ 0.05). The structural model illustrates the effects of using social media on the social skills and nurse-patient interaction of nurses and emphasizes the need for implementing institutional policies on the judicious use and application of social media in the workplace. Further, social skills development programs geared toward having a balanced social skill must be implemented. Copyright © 2018 Elsevier Ltd. All rights reserved.

New links between the Chicxulub impact structure and the Cretaceous/Tertiary boundary

USGS Publications Warehouse

Sharpton, V.L.; Dalrymple, G.B.; Marin, L.E.; Ryder, G.; Schuraytz, B.C.; Urrutia-Fucugauchi, J.

1992-01-01

THE 200-km-diameter Chicxulub structure1-3 in northern Yucatan, Mexico has emerged as the prime candidate for the Cretaceous/Tertiary (K/T) boundary impact crater3-6. Concentric geophysical anomalies associated with enigmatic occurrences of Upper Cretaceous breccias and andesitic rocks led Penfield and Camargo1 to suspect that this structure was a buried impact basin. More recently, the discovery of shocked quartz grains in a Chicxulub breccia3, and chemical similarities between Chicxulub rocks and K/T tektite-like glasses3-6 have been advanced as evidence that the Chicxulub structure is a K/T impact site. Here we present evidence from core samples that Chicxulub is indeed a K/T source crater, and can apparently account for all the evidence of impact distributed globally at the K/T boundary without the need for simultaneous multiple impacts or comet showers. Shocked breccia clasts found in the cores are similar to shocked lithic fragments found worldwide in the K/T boundary ejecta layer7,8. The Chicxulub melt rocks that we studied contain anomalously high levels of iridium (up to 13.5 parts per 109), also consistent with the indium-enriched K/T boundary layer9. Our best estimate of the crystallization age of these melt rocks, as determined by 40Ar/39Ar analyses, is 65.2??0.4 (1??) Myr, in good agreement with the mean plateau age of 64.98 ?? 0.05 Myr recently reported10. Furthermore, these melt rocks acquired a remanent magnetization indicating that they cooled during an episode of reversed geomagnetic polarity. The only such episode consistent with 40Ar/39Ar constraints is chron 29R, which includes the K/T boundary.

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.

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.

Variation in Inflammatory/Regulatory Cytokines in Secondary, Tertiary, and Quaternary Challenges with Dengue Virus

PubMed Central

Sierra, Beatriz; Pérez, Ana B.; Alvarez, Mayling; García, Gissel; Vogt, Katrin; Aguirre, Eglys; Schmolke, Kathrin; Volk, Hans-Dieter; Guzmán, María G.

2012-01-01

Secondary heterologous dengue infection is a risk factor for severe disease manifestations because of the immune-enhancement phenomenon. Succeeding clinical infections are seldom reported, and the clinical course of tertiary and quaternary dengue infections is not clear. Cuba represents a unique environment to study tertiary/quaternary dengue infections in a population with known clinical and serologic dengue markers and no dengue endemicity. We took advantage of this exceptional epidemiologic condition to study the effect of primary, secondary, tertiary, and quaternary dengue infection exposure on the expression of pro-inflammatory and regulatory cytokines, critical in dengue infection pathogenesis, by using a dengue infection ex vivo model. Whereas secondary exposure induced a high cytokine response, we found a significantly lower expression of tumor necrosis factor-α, interferon-γ, interleukin-10, and tumor growth factor-β after tertiary and quaternary infectious challenge. Significant differences in expression of the cytokines were seen between the dengue immune profiles, suggesting that the sequence in which the immune system encounters serotypes may be important in determining the nature of the immune response to subsequent infections. PMID:22802438

The equity imperative in tertiary education: Promoting fairness and efficiency

NASA Astrophysics Data System (ADS)

Salmi, Jamil; Bassett, Roberta Malee

2014-06-01

While the share of the tertiary education age cohort (19-25) which is being given the opportunity to study has increased worldwide over the past two decades, this does not in fact translate into reduced inequality. For many young people, especially in the developing world, major obstacles such as disparities in terms of gender, minority population membership or disabilities as well as academic and financial barriers are still standing in their way. The authors of this article propose a conceptual framework to analyse equity issues in tertiary education and document the scope, significance and consequences of disparities in tertiary education opportunities. They throw some light on the main determinants of these inequalities and offer suggestions about effective equity promotion policies directed towards widening participation and improving the chances of success of underprivileged youths in order to create societies which uphold humanistic values.

Tertiary Lymphoid Structure-Associated B Cells are Key Players in Anti-Tumor Immunity

PubMed Central

Germain, Claire; Gnjatic, Sacha; Dieu-Nosjean, Marie-Caroline

2015-01-01

It is now admitted that the immune system plays a major role in tumor control. Besides the existence of tumor-specific T cells and B cells, many studies have demonstrated that high numbers of tumor-infiltrating lymphocytes are associated with good clinical outcome. In addition, not only the density but also the organization of tumor-infiltrating immune cells has been shown to determine patient survival. Indeed, more and more studies describe the development within the tumor microenvironment of tertiary lymphoid structures (TLS), whose presence has a positive impact on tumor prognosis. TLS are transient ectopic lymphoid aggregates displaying the same organization and functionality as canonical secondary lymphoid organs, with T-cell-rich and B-cell-rich areas that are sites for the differentiation of effector and memory T cells and B cells. However, factors favoring the emergence of such structures within tumors still need to be fully characterized. In this review, we survey the state of the art of what is known about the general organization, induction, and functionality of TLS during chronic inflammation, and more especially in cancer, with a particular focus on the B-cell compartment. We detail the role played by TLS B cells in anti-tumor immunity, both as antigen-presenting cells and tumor antigen-specific antibody-secreting cells, and raise the question of the capacity of chemotherapeutic and immunotherapeutic agents to induce the development of TLS within tumors. Finally, we explore how to take advantage of our knowledge on TLS B cells to develop new therapeutic tools. PMID:25755654

Birth preparedness and complication readiness among prenatal attendees in a teaching hospital in South West Nigeria.

PubMed

Aduloju, Olusola P; Akintayo, Akinyemi A; Aduloju, Tolulope; Akin-Akintayo, Oladunni O

2017-11-01

To assess birth preparedness and complication readiness (BPCR) as well as knowledge of danger signs during pregnancy, labor/delivery, and the postpartum period. A cross-sectional study was undertaken of pregnant women attending the prenatal clinic at a tertiary hospital in Nigeria between October and December 2016. A pretested and structured questionnaire was used to collect data on BPCR, and logistic regression was performed to determine factors affecting BPCR. Of 325 participants, 274 (84.3%) had knowledge of BPCR components, and 265 (81.5%) were well prepared for birth and its complications. However, only 89 (27.4%) knew key danger signs during labor/delivery and 81 (24.9%) knew those in the first 2 days after delivery. Older age, higher parity, tertiary education of women, paid employment of women and their spouses, higher social class, frequent prenatal visits, and knowledge of danger signs were significantly associated with BPCR (P<0.05). Higher parity, maternal government employment, and knowledge of danger signs during pregnancy remained determinants of BPCR on logistic regression (P<0.05). Although there was a high level of knowledge and practice of BPCR, knowledge of key danger signs was low. Therefore, prenatal education needs to be improved with an emphasis on teaching pregnant women to recognize key danger signs. © 2017 International Federation of Gynecology and Obstetrics.

Unraveling the meaning of chemical shifts in protein NMR.

PubMed

Berjanskii, Mark V; Wishart, David S

2017-11-01

Chemical shifts are among the most informative parameters in protein NMR. They provide wealth of information about protein secondary and tertiary structure, protein flexibility, and protein-ligand binding. In this report, we review the progress in interpreting and utilizing protein chemical shifts that has occurred over the past 25years, with a particular focus on the large body of work arising from our group and other Canadian NMR laboratories. More specifically, this review focuses on describing, assessing, and providing some historical context for various chemical shift-based methods to: (1) determine protein secondary and super-secondary structure; (2) derive protein torsion angles; (3) assess protein flexibility; (4) predict residue accessible surface area; (5) refine 3D protein structures; (6) determine 3D protein structures and (7) characterize intrinsically disordered proteins. This review also briefly covers some of the methods that we previously developed to predict chemical shifts from 3D protein structures and/or protein sequence data. It is hoped that this review will help to increase awareness of the considerable utility of NMR chemical shifts in structural biology and facilitate more widespread adoption of chemical-shift based methods by the NMR spectroscopists, structural biologists, protein biophysicists, and biochemists worldwide. This article is part of a Special Issue entitled: Biophysics in Canada, edited by Lewis Kay, John Baenziger, Albert Berghuis and Peter Tieleman. Copyright © 2017 Elsevier B.V. All rights reserved.

Specific and total N-nitrosamines formation potentials of nitrogenous micropollutants during chloramination.

PubMed

Piazzoli, Andrea; Breider, Florian; Aquillon, Caroline Gachet; Antonelli, Manuela; von Gunten, Urs

2018-05-15

N-nitrosamines are a group of potent human carcinogens that can be formed during oxidative treatment of drinking water and wastewater. Many tertiary and quaternary amines present in consumer products (e.g., pharmaceuticals, personal care and household products) are known to be N-nitrosodimethylamine (NDMA) precursors during chloramination, but the formation of other N-nitrosamines has been rarely studied. This study investigates the specific and total N-nitrosamine (TONO) formation potential (FP) of various precursors from nitrogen-containing micropollutants (chlorhexidine, metformin, benzalkonium chloride and cetyltrimethylammonium chloride) and tertiary and quaternary model amines (trimethyl amine, N,N-dimethylbutyl amine, N,N-dimethylbenzyl amine and tetramethyl ammonium). All the studied nitrogenous micropollutants displayed quantifiable TONO FP, with molar yields in the range 0.04-11.92%. However, the observed TONO pools constituted mostly of uncharacterized species, not included in US-EPA 8270 N-nitrosamines standard mix. Only the quaternary ammonium compound benzalkonium chloride showed quantifiable NDMA FP (0.56% molar yield), however, explaining only a minor fraction of the observed TONO FP. The studied model amines showed molar NDMA yields from 0.10% (trimethyl amine) to 5.05% (N,N-dimethylbenzyl amine), very similar to the molar TONO yields. The comparison of the FPs of micropollutants and model compounds showed that the presence of electron donating functional groups (such as a benzyl group) in tertiary and quaternary amine precursors leads to a higher formation of NDMA and uncharacterized N-nitrosamines, respectively. LC-qTOF screening of a list of proposed N-nitrosamine structures has enabled to identify a novel N-nitrosamine (N-nitroso-N-methyldodecylamine) from the chloramination of benzalkonium chloride. This finding supports the hypothesis that different functional groups in quaternary amines can act as leaving groups during chloramination and form differing N-nitrosamine structures at significant yield. Molar TONO yields determined for micropollutants were finally validated under experimental conditions closer to real water matrices, confirming their representativeness also for lower concentration ranges. Copyright © 2018 Elsevier Ltd. All rights reserved.

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.

Knowledge and beliefs about breastfeeding are not determinants for successful breastfeeding.

PubMed

Ishak, Shareena; Adzan, Nur Azeanny M; Quan, Lee K; Shafie, M Hasli; Rani, Nor Azila; Ramli, Kazzoma G

2014-01-01

A cross-sectional prospective study was performed to assess knowledge and attitude toward breastfeeding among mothers in a tertiary hospital in Malaysia and its influence on their breastfeeding practices. Two hundred thirteen women who had delivered healthy babies at term were enrolled. A structured questionnaire containing demographic data and the Iowa Infant Feeding Attitude Score were used, followed by a telephone interview after 8 weeks to determine the feeding outcome. Women of Malay ethnicity with higher education level who had received breastfeeding counseling had a significantly more favorable attitude toward breastfeeding. Ethnicity was found to be a significant determinant in the success of breastfeeding, whereas returning to work was a major reason for discontinuing breastfeeding. In ensuring a successful breastfeeding practice, apart from knowledge and attitude, issues surrounding culture and traditions as well as improving deliverance of readily available support should be addressed.

Knowledge and Beliefs About Breastfeeding Are Not Determinants for Successful Breastfeeding

PubMed Central

Adzan, Nur Azeanny M.; Quan, Lee K.; Shafie, M. Hasli; Rani, Nor Azila; Ramli, Kazzoma G.

2014-01-01

Abstract A cross-sectional prospective study was performed to assess knowledge and attitude toward breastfeeding among mothers in a tertiary hospital in Malaysia and its influence on their breastfeeding practices. Two hundred thirteen women who had delivered healthy babies at term were enrolled. A structured questionnaire containing demographic data and the Iowa Infant Feeding Attitude Score were used, followed by a telephone interview after 8 weeks to determine the feeding outcome. Women of Malay ethnicity with higher education level who had received breastfeeding counseling had a significantly more favorable attitude toward breastfeeding. Ethnicity was found to be a significant determinant in the success of breastfeeding, whereas returning to work was a major reason for discontinuing breastfeeding. In ensuring a successful breastfeeding practice, apart from knowledge and attitude, issues surrounding culture and traditions as well as improving deliverance of readily available support should be addressed. PMID:24893127

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.

ProDaMa: an open source Python library to generate protein structure datasets.

PubMed

Armano, Giuliano; Manconi, Andrea

2009-10-02

The huge difference between the number of known sequences and known tertiary structures has justified the use of automated methods for protein analysis. Although a general methodology to solve these problems has not been yet devised, researchers are engaged in developing more accurate techniques and algorithms whose training plays a relevant role in determining their performance. From this perspective, particular importance is given to the training data used in experiments, and researchers are often engaged in the generation of specialized datasets that meet their requirements. To facilitate the task of generating specialized datasets we devised and implemented ProDaMa, an open source Python library than provides classes for retrieving, organizing, updating, analyzing, and filtering protein data. ProDaMa has been used to generate specialized datasets useful for secondary structure prediction and to develop a collaborative web application aimed at generating and sharing protein structure datasets. The library, the related database, and the documentation are freely available at the URL http://iasc.diee.unica.it/prodama.

A Pseudo-Atomic Model of the COPII Cage Obtained from CryoEM and Mass Spectrometry Analyses

PubMed Central

Noble, Alex J.; Zhang, Qian; O’Donnell, Jason; Hariri, Hanaa; Bhattacharya, Nilakshee; Marshall, Alan G.

2012-01-01

COPII vesicles transport proteins from the ER to the Golgi apparatus. Previous cryoEM structures of the COPII cage lacked the resolution necessary to determine the residues of Sec13 and Sec31 that mediate assembly and flexibility of the COPII cage. Here we present a 12Å-resolution structure of the COPII cage, where the tertiary structure of Sec13 and Sec31 is clearly identifiable. We employ this structure and a homology model of the Sec13-Sec31 complex to create a reliable pseudo-atomic model of the COPII cage. We combined this model with hydrogen/deuterium exchange mass spectrometry analysis to characterize four distinct contact regions at the vertices of the COPII cage. Furthermore, we found that the 2-fold symmetry of the Sec31 dimeric region of Sec13-31 is broken on cage formation, and that the resulting hinge is essential to form the proper edge geometry in COPII cages. PMID:23262493

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.

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.

Monoclonal Antibody Interactions with Micro- and Nanoparticles: Adsorption, Aggregation and Accelerated Stress Studies

PubMed Central

Bee, Jared S.; Chiu, David; Sawicki, Suzanne; Stevenson, Jennifer L.; Chatterjee, Koustuv; Freund, Erwin; Carpenter, John F.; Randolph, Theodore W.

2009-01-01

Therapeutic proteins are exposed to various wetted surfaces that could shed sub-visible particles. In this work we measured the adsorption of a monoclonal antibody (mAb) to various microparticles, characterized the adsorbed mAb secondary structure, and determined the reversibility of adsorption. We also developed and used a front-face fluorescence quenching method to determine that the mAb tertiary structure was near-native when adsorbed to glass, cellulose and silica. Initial adsorption to each of the materials tested was rapid. During incubation studies, exposure to the air-water interface was a significant cause of aggregation but acted independently of the effects of microparticles. Incubations with glass, cellulose, stainless steel or Fe2O3 microparticles gave very different results. Cellulose preferentially adsorbed aggregates from solution. Glass and Fe2O3 adsorbed the mAb but did not cause aggregation. Adsorption to stainless steel microparticles was irreversible, and caused appearance of soluble aggregates upon incubation. The secondary structure of mAb adsorbed to glass and cellulose was near-native. We suggest that the protocol described in this work could be a useful preformulation stress screening tool to determine the sensitivity of a therapeutic protein to exposure to common surfaces encountered during processing and storage. PMID:19492408

Conformational changes in the expression domain of the Escherichia coli thiM riboswitch

PubMed Central

Rentmeister, Andrea; Mayer, Günter; Kuhn, Nicole; Famulok, Michael

2007-01-01

The thiM riboswitch contains an aptamer domain that adaptively binds the coenzyme thiamine pyrophosphate (TPP). The binding of TPP to the aptamer domain induces structural rearrangements that are relayed to a second domain, the so-called expression domain, thereby interfering with gene expression. The recently solved crystal structures of the aptamer domains of the thiM riboswitches in complex with TPP revealed how TPP stabilizes secondary and tertiary structures in the RNA ligand complex. To understand the global modes of reorganization between the two domains upon metabolite binding the structure of the entire riboswitch in presence and absence of TPP needs to be determined. Here we report the secondary structure of the entire thiM riboswitch from Escherichia coli in its TPP-free form and its transition into the TPP-bound variant, thereby depicting domains of the riboswitch that serve as communication links between the aptamer and the expression domain. Furthermore, structural probing provides an explanation for the lack of genetic control exerted by a riboswitch variant with mutations in the expression domain that still binds TPP. PMID:17517779

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

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).

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

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.

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

Identification of N-Terminal Lobe Motifs that Determine the Kinase Activity of the Catalytic Domains and Regulatory Strategies of Src and Csk Protein Tyrosine Kinases†

PubMed Central

Huang, Kezhen; Wang, Yue-Hao; Brown, Alex; Sun, Gongqin

2009-01-01

Csk and Src protein tyrosine kinases are structurally homologous, but use opposite regulatory strategies. The isolated catalytic domain of Csk is intrinsically inactive and is activated by interactions with the regulatory SH3 and SH2 domains, while the isolated catalytic domain of Src is intrinsically active and is suppressed by interactions with the regulatory SH3 and SH2 domains. The structural basis for why one isolated catalytic domain is intrinsically active while the other is inactive is not clear. In this current study, we identify the structural elements in the N-terminal lobe of the catalytic domain that render the Src catalytic domain active. These structural elements include the α-helix C region, a β-turn between the β-4 and β-5 strands, and an Arg residue at the beginning of the catalytic domain. These three motifs interact with each other to activate the Src catalytic domain, but the equivalent motifs in Csk directly interact with the regulatory domains that are important for Csk activation. The Src motifs can be grafted to the Csk catalytic domain to obtain an active Csk catalytic domain. These results, together with available Src and Csk tertiary structures, reveal an important structural switch that determines the kinase activity of a catalytic domain and dictates the regulatory strategy of a kinase. PMID:19244618

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.

Sequencing proteins with transverse ionic transport in nanochannels.

PubMed

Boynton, Paul; Di Ventra, Massimiliano

2016-05-03

De novo protein sequencing is essential for understanding cellular processes that govern the function of living organisms and all sequence modifications that occur after a protein has been constructed from its corresponding DNA code. By obtaining the order of the amino acids that compose a given protein one can then determine both its secondary and tertiary structures through structure prediction, which is used to create models for protein aggregation diseases such as Alzheimer's Disease. Here, we propose a new technique for de novo protein sequencing that involves translocating a polypeptide through a synthetic nanochannel and measuring the ionic current of each amino acid through an intersecting perpendicular nanochannel. We find that the distribution of ionic currents for each of the 20 proteinogenic amino acids encoded by eukaryotic genes is statistically distinct, showing this technique's potential for de novo protein sequencing.

Eclipsing Binaries with Possible Tertiary Components

NASA Astrophysics Data System (ADS)

Snyder, LeRoy F.

2013-05-01

Many eclipsing binary star systems (EBS) show long-term variations in their orbital periods which are evident in their O-C (observed minus calculated period) diagrams. This research carried out an analysis of 324 eclipsing binary systems taken from the systems analyzed in the Bob Nelson's O-C Files database. Of these 18 systems displayed evidence of periodic variations of the arrival times of the eclipses. These rates of period changes are sinusoidal variations. The sinusoidal character of these variations is suggestive of Keplerian motion caused by an orbiting companion. The reason for these changes is unknown, but mass loss, apsidal motion, magnetic activity and the presence of a third body have been proposed. This paper has assumed light time effect as the cause of the sinusoidal variations caused by the gravitational pull of a tertiary companion orbiting around the eclipsing binary systems. An observed minus calculated (O-C) diagram of the 324 systems was plotted using a quadratic ephemeris to determine if the system displayed a sinusoidal trend in theO-C residuals. After analysis of the 18 systems, seven systems, AW UMa, BB PEG, OO Aql, V508 Oph, VW Cep, WCrv and YY ERI met the benchmark of the criteria of a possible orbiting companion. The other 11 systems displayed a sinusoidal variation in the O-C residuals of the primary eclipses but these systems in the Bob Nelson's O-C Files did not contain times of minimum (Tmin) of the secondary eclipses and therefore not conclusive in determining the presents of the effects of a tertiary companion. An analysis of the residuals of the seven systems yields a light-time semi-amplitude, orbital period, eccentricity and mass of the tertiary companion as the amplitude of the variation is proportional to the mass, period and inclination of the 3rd orbiting body. Knowing the low mass of the tertiary body in the seven cases the possibility of five of these tertiary companions being brown dwarfs is discussed.

The pH-dependent tertiary structure of a designed helix-loop-helix dimer.

PubMed

Dolphin, G T; Baltzer, L

1997-01-01

De novo designed helix-loop-helix motifs can fold into well-defined tertiary structures if residues or groups of residues are incorporated at the helix-helix boundary to form helix-recognition sites that restrict the conformational degrees of freedom of the helical segments. Understanding the relationship between structure and function of conformational constraints therefore forms the basis for the engineering of non-natural proteins. This paper describes the design of an interhelical HisH+-Asp- hydrogen-bonded ion pair and the conformational stability of the folded helix-loop-helix motif. GTD-C, a polypeptide with 43 amino acid residues, has been designed to fold into a hairpin helix-loop-helix motif that can dimerise to form a four-helix bundle. The folded motif is in slow conformational exchange on the NMR timescale and has a well-dispersed 1H NMR spectrum, a narrow temperature interval for thermal denaturation and a near-UV CD spectrum with some fine structure. The conformational stability is pH dependent with an optimum that corresponds to the pH for maximum formation of a hydrogen-bonded ion pair between HisH17+ in helix I and Asp27- in helix II. The formation of an interhelical salt bridge is strongly suggested by the pH dependence of a number of spectroscopic probes to generate a well-defined tertiary structure in a designed helix-loop-helix motif. The thermodynamic stability of the folded motif is not increased by the formation of the salt bridge, but neighbouring conformations are destabilised. The use of this novel design principle in combination with hydrophobic interactions that provide sufficient binding energy in the folded structure should be of general use in de novo design of native-like proteins.

Fast protein tertiary structure retrieval based on global surface shape similarity.

PubMed

Sael, Lee; Li, Bin; La, David; Fang, Yi; Ramani, Karthik; Rustamov, Raif; Kihara, Daisuke

2008-09-01

Characterization and identification of similar tertiary structure of proteins provides rich information for investigating function and evolution. The importance of structure similarity searches is increasing as structure databases continue to expand, partly due to the structural genomics projects. A crucial drawback of conventional protein structure comparison methods, which compare structures by their main-chain orientation or the spatial arrangement of secondary structure, is that a database search is too slow to be done in real-time. Here we introduce a global surface shape representation by three-dimensional (3D) Zernike descriptors, which represent a protein structure compactly as a series expansion of 3D functions. With this simplified representation, the search speed against a few thousand structures takes less than a minute. To investigate the agreement between surface representation defined by 3D Zernike descriptor and conventional main-chain based representation, a benchmark was performed against a protein classification generated by the combinatorial extension algorithm. Despite the different representation, 3D Zernike descriptor retrieved proteins of the same conformation defined by combinatorial extension in 89.6% of the cases within the top five closest structures. The real-time protein structure search by 3D Zernike descriptor will open up new possibility of large-scale global and local protein surface shape comparison. 2008 Wiley-Liss, Inc.

Updates to Blast Injury Criteria Models for Nuclear Casualty Estimation

DTIC Science & Technology

2015-12-01

the likelihood of blast-related injury use a two-step process. First, the maximum velocity obtained by the human body or secondary missile is determined...the human body . Secondary injuries are caused by missiles that are accelerated by the blast wave. Tertiary injuries are caused by the acceleration of...the human body and the ensuing deceleration. In this work, we focus on secondary and tertiary injuries. Because of the dramatic effects experienced

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.

Amino acid sequence analysis of the annexin super-gene family of proteins.

PubMed

Barton, G J; Newman, R H; Freemont, P S; Crumpton, M J

1991-06-15

The annexins are a widespread family of calcium-dependent membrane-binding proteins. No common function has been identified for the family and, until recently, no crystallographic data existed for an annexin. In this paper we draw together 22 available annexin sequences consisting of 88 similar repeat units, and apply the techniques of multiple sequence alignment, pattern matching, secondary structure prediction and conservation analysis to the characterisation of the molecules. The analysis clearly shows that the repeats cluster into four distinct families and that greatest variation occurs within the repeat 3 units. Multiple alignment of the 88 repeats shows amino acids with conserved physicochemical properties at 22 positions, with only Gly at position 23 being absolutely conserved in all repeats. Secondary structure prediction techniques identify five conserved helices in each repeat unit and patterns of conserved hydrophobic amino acids are consistent with one face of a helix packing against the protein core in predicted helices a, c, d, e. Helix b is generally hydrophobic in all repeats, but contains a striking pattern of repeat-specific residue conservation at position 31, with Arg in repeats 4 and Glu in repeats 2, but unconserved amino acids in repeats 1 and 3. This suggests repeats 2 and 4 may interact via a buried saltbridge. The loop between predicted helices a and b of repeat 3 shows features distinct from the equivalent loop in repeats 1, 2 and 4, suggesting an important structural and/or functional role for this region. No compelling evidence emerges from this study for uteroglobin and the annexins sharing similar tertiary structures, or for uteroglobin representing a derivative of a primordial one-repeat structure that underwent duplication to give the present day annexins. The analyses performed in this paper are re-evaluated in the Appendix, in the light of the recently published X-ray structure for human annexin V. The structure confirms most of the predictions and shows the power of techniques for the determination of tertiary structural information from the amino acid sequences of an aligned protein family.

Using molecular principal axes for structural comparison: determining the tertiary changes of a FAB antibody domain induced by antigenic binding

PubMed Central

Silverman, B David

2007-01-01

Background Comparison of different protein x-ray structures has previously been made in a number of different ways; for example, by visual examination, by differences in the locations of secondary structures, by explicit superposition of structural elements, e.g. α-carbon atom locations, or by procedures that utilize a common symmetry element or geometrical feature of the structures to be compared. Results A new approach is applied to determine the structural changes that an antibody protein domain experiences upon its interaction with an antigenic target. These changes are determined with the use of two different, however comparable, sets of principal axes that are obtained by diagonalizing the second-order tensors that yield the moments-of-geometry as well as an ellipsoidal characterization of domain shape, prior to and after interaction. Determination of these sets of axes for structural comparison requires no internal symmetry features of the domains, depending solely upon their representation in three-dimensional space. This representation may involve atomic, Cα, or residue centroid coordinates. The present analysis utilizes residue centroids. When the structural changes are minimal, the principal axes of the domains, prior to and after interaction, are essentially comparable and consequently may be used for structural comparison. When the differences of the axes cannot be neglected, but are nevertheless slight, a smaller relatively invariant substructure of the domains may be utilized for comparison. The procedure yields two distance metrics for structural comparison. First, the displacements of the residue centroids due to antigenic binding, referenced to the ellipsoidal principal axes, are noted. Second, changes in the ellipsoidal distances with respect to the non-interacting structure provide a direct measure of the spatial displacements of the residue centroids, towards either the interior or exterior of the domain. Conclusion With use of x-ray data from the protein data bank (PDB), these two metrics are shown to highlight, in a manner different from before, the structural changes that are induced in the overall domains as well as in the H3 loops of the complementarity-determining regions (CDR) upon FAB antibody binding to a truncated and to a synthetic hemagglutinin viral antigenic target. PMID:17996091

Structure of Urtica dioica agglutinin isolectin I: dimer formation mediated by two zinc ions bound at the sugar-binding site.

PubMed

Harata, K; Schubert, W D; Muraki, M

2001-11-01

Ultica dioica agglutinin, a plant lectin from the stinging nettle, consists of a total of seven individual isolectins. One of these structures, isolectin I, was determined at 1.9 A resolution by the X-ray method. The crystals belong to the space group P2(1) and the asymmetric unit contains two molecules related by local twofold symmetry. The molecule consists of two hevein-like chitin-binding domains lacking distinct secondary structure, but four disulfide bonds in each domain maintain the tertiary structure. The backbone structure of the two independent molecules is essentially identical and this is similarly true of the sugar-binding sites. In the crystal, the C-terminal domains bind Zn(2+) ions at the sugar-binding site. Owing to their location near a pseudo-twofold axis, the two zinc ions link the two independent molecules in a tail-to-tail arrangement: thus, His47 of molecule 1 and His67 of molecule 2 coordinate the first zinc ion, while the second zinc ion links Asp75 of molecule 1 and His47 of molecule 2.

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.

Designing cooperatively folded abiotic uni- and multimolecular helix bundles

NASA Astrophysics Data System (ADS)

de, Soumen; Chi, Bo; Granier, Thierry; Qi, Ting; Maurizot, Victor; Huc, Ivan

2018-01-01

Abiotic foldamers, that is foldamers that have backbones chemically remote from peptidic and nucleotidic skeletons, may give access to shapes and functions different to those of peptides and nucleotides. However, design methodologies towards abiotic tertiary and quaternary structures are yet to be developed. Here we report rationally designed interactional patterns to guide the folding and assembly of abiotic helix bundles. Computational design facilitated the introduction of hydrogen-bonding functionalities at defined locations on the aromatic amide backbones that promote cooperative folding into helix-turn-helix motifs in organic solvents. The hydrogen-bond-directed aggregation of helices not linked by a turn unit produced several thermodynamically and kinetically stable homochiral dimeric and trimeric bundles with structures that are distinct from the designed helix-turn-helix. Relative helix orientation within the bundles may be changed from parallel to tilted on subtle solvent variations. Altogether, these results prefigure the richness and uniqueness of abiotic tertiary structure behaviour.

Nickel-Catalyzed Coupling Reactions of Alkyl Electrophiles, Including Unactivated Tertiary Halides, to Generate Carbon–Boron Bonds

PubMed Central

Dudnik, Alexander S.

2012-01-01

Through the use of a catalyst formed in situ from NiBr2•diglyme and a pybox ligand (both of which are commercially available), we have achieved our first examples of coupling reactions of unactivated tertiary alkyl electrophiles, as well as our first success with nickel-catalyzed couplings that generate bonds other than C–C bonds. Specifically, we have determined that this catalyst accomplishes Miyaura-type borylations of unactivated tertiary, secondary, and primary alkyl halides with diboron reagents to furnish alkylboronates, a family of compounds with substantial (and expanding) utility, under mild conditions; indeed, the umpolung borylation of a tertiary alkyl bromide can be achieved at a temperature as low as −10 °C. The method exhibits good functional-group compatibility and is regiospecific, both of which can be issues with traditional approaches to the synthesis of alkylboronates. In contrast to seemingly related nickel-catalyzed C–C bond-forming processes, tertiary halides are more reactive than secondary or primary halides in this nickel-catalyzed C–B bond-forming reaction; this divergence is particularly noteworthy in view of the likelihood that both transformations follow an inner-sphere electron-transfer pathway for oxidative addition. PMID:22668072

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.

Structural Characteristic of the Initial Unfolded State on Refolding Determines Catalytic Efficiency of the Folded Protein in Presence of Osmolytes

PubMed Central

Warepam, Marina; Sharma, Gurumayum Suraj; Dar, Tanveer Ali; Khan, Md. Khurshid Alam; Singh, Laishram Rajendrakumar

2014-01-01

Osmolytes are low molecular weight organic molecules accumulated by organisms to assist proper protein folding, and to provide protection to the structural integrity of proteins under denaturing stress conditions. It is known that osmolyte-induced protein folding is brought by unfavorable interaction of osmolytes with the denatured/unfolded states. The interaction of osmolyte with the native state does not significantly contribute to the osmolyte-induced protein folding. We have therefore investigated if different denatured states of a protein (generated by different denaturing agents) interact differently with the osmolytes to induce protein folding. We observed that osmolyte-assisted refolding of protein obtained from heat-induced denatured state produces native molecules with higher enzyme activity than those initiated from GdmCl- or urea-induced denatured state indicating that the structural property of the initial denatured state during refolding by osmolytes determines the catalytic efficiency of the folded protein molecule. These conclusions have been reached from the systematic measurements of enzymatic kinetic parameters (K m and k cat), thermodynamic stability (T m and ΔH m) and secondary and tertiary structures of the folded native proteins obtained from refolding of various denatured states (due to heat-, urea- and GdmCl-induced denaturation) of RNase-A in the presence of various osmolytes. PMID:25313668

Flexibility of the Cu,Zn superoxide dismutase structure investigated at 0.57 GPa.

PubMed

Ascone, Isabella; Savino, Carmelinda; Kahn, Richard; Fourme, Roger

2010-06-01

The 2 A resolution crystal structure of bovine erythrocyte Cu,Zn superoxide dismutase (CuZnSOD) has been determined by X-ray diffraction at high pressure (0.57 GPa) and room temperature. At 0.57 GPa the secondary, tertiary and quaternary structures are similar to other previously determined bovine erythrocyte CuZnSOD structures. Nevertheless, pressure has a localized impact on the atomic coordinates of C(alpha) atoms and on side chains. The compression of the crystal and of the protein backbone is anisotropic. This anisotropy is discussed, taking into account intermolecular contacts and protein conformation. Pressure perturbation highlights the more flexible zones in the protein such as the electrostatic loop. At 0.57 GPa, a global shift of the dimetallic sites in both subunits and changes in the oxidation state of Cu were observed. The flexibility of the electrostatic loop may be useful for the interaction of different metal carriers in the copper-uptake process, whereas the flexibility of the metal sites involved in the activity of the protein could contribute to explaining the ubiquitous character of CuZnSODs, which are found in organisms living in very different conditions, including the deep-sea environment. This work illustrates the potential of combining X-ray crystallography with high pressure to promote and stabilize higher energy conformational substates.

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.

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

Quantitative evaluation of protein conformation in pharmaceuticals using cross-linking reactions coupled with LC-MS/MS analysis.

PubMed

Yamaguchi, Hideto; Hirakura, Yutaka; Shirai, Hiroki; Mimura, Hisashi; Toyo'oka, Toshimasa

2011-06-01

The need for a simple and high-throughput method for identifying the tertiary structure of protein pharmaceuticals has increased. In this study, a simple method for mapping the protein fold is proposed for use as a complementary quality test. This method is based on cross-linking a protein using a [bis(sulfosuccinimidyl)suberate (BS(3))], followed by peptide mapping by LC-MS. Consensus interferon (CIFN) was used as the model protein. The tryptic map obtained via liquid chromatography tandem mass spectroscopy (LC-MS/MS) and the mass mapping obtained via matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy were used to identify cross-linked peptides. While LC-MS/MS analyses found that BS(3) formed cross-links in the loop region of the protein, which was regarded as the biologically active site, sodium dodecyl-sulfate polyacrylamide gel electrophoresis demonstrated that cross-linking occurred within a protein molecule, but not between protein molecules. The occurrence of cross-links at the active site depends greatly on the conformation of the protein, which is determined by the denaturing conditions. Quantitative evaluation of the tertiary structure of CIFN was thus possible by monitoring the amounts of cross-linked peptides generated. Assuming that background information is available at the development stage, this method may be applicable to process development as a complementary test for quality control. Copyright © 2011 Elsevier B.V. All rights reserved.

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.

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.

Complementary and alternative medicine (CAM) use in children with functional abdominal pain (FAP) and irritable bowel syndrome (IBS) differs in tertiary vs. primary care and is related to mother's view of child disability

USDA-ARS?s Scientific Manuscript database

We sought to determine if CAM use was greater in children in tertiary vs. primary care, and whether child or parent report of pain characteristics, and/or child and mother's psychological characteristics differed between those who did/did not use CAM. We identified children 7-10 years of age with FA...

Do family and neighbourhood matter in secondary school completion? A multilevel study of determinants and their interactions in a life-course perspective.

PubMed

Myhr, Arnhild; Lillefjell, Monica; Espnes, Geir Arild; Halvorsen, Thomas

2017-01-01

Completion of secondary education is important for individuals' future health and health behaviour. The fundamental purpose of this study is to investigate the variation and clustering of school completion in families and neighbourhoods. Secondly, we aim to examine the impact of individuals' family structure and neighbourhood of residence and examine to what extent parental education level moderates these associations. Longitudinal register data for 30% of the entire Norwegian population aged 21-27 years in 2010 (N = 107,003) was extracted from Statistic Norway´s event database. Three-level logistic regression models, which incorporated individual, family, and neighbourhood contextual factors, were applied to estimate the family and neighbourhood general contextual effects and detect possible educational differences in the impact of family structure and urban place of residence in school completion. Completion rates were significantly higher within families with higher education level (79% in tertiary educated families vs. 61% and 48% in secondary and primary educated families respectively) and were strongly correlated within families (ICC = 39.6) and neighbourhoods (ICC = 5.7). Several structural factors at the family level negatively associated with school completion (e.g., family disruption, large family size, and young maternal age) were more prevalent and displayed more negative impact among primary educated individuals. Urban residence was associated with school completion, but only among the tertiary educated. Investment in the resources in the individuals' immediate surroundings, including family and neighbourhood, may address a substantial portion of the social inequalities in the completion of upper secondary education. The high intra-familial correlation in school completion suggests that public health policies and future research should acknowledge family environments in order to improve secondary education completion rates among young people within lower educated families.

RNAmutants: a web server to explore the mutational landscape of RNA secondary structures

PubMed Central

Waldispühl, Jerome; Devadas, Srinivas; Berger, Bonnie; Clote, Peter

2009-01-01

The history and mechanism of molecular evolution in DNA have been greatly elucidated by contributions from genetics, probability theory and bioinformatics—indeed, mathematical developments such as Kimura's neutral theory, Kingman's coalescent theory and efficient software such as BLAST, ClustalW, Phylip, etc., provide the foundation for modern population genetics. In contrast to DNA, the function of most noncoding RNA depends on tertiary structure, experimentally known to be largely determined by secondary structure, for which dynamic programming can efficiently compute the minimum free energy secondary structure. For this reason, understanding the effect of pointwise mutations in RNA secondary structure could reveal fundamental properties of structural RNA molecules and improve our understanding of molecular evolution of RNA. The web server RNAmutants provides several efficient tools to compute the ensemble of low-energy secondary structures for all k-mutants of a given RNA sequence, where k is bounded by a user-specified upper bound. As we have previously shown, these tools can be used to predict putative deleterious mutations and to analyze regulatory sequences from the hepatitis C and human immunodeficiency genomes. Web server is available at http://bioinformatics.bc.edu/clotelab/RNAmutants/, and downloadable binaries at http://rnamutants.csail.mit.edu/. PMID:19531740

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

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.

Metrology for Trending Alignment of the James Webb Space Telescope Before and After Ambient Environmental Testing

NASA Technical Reports Server (NTRS)

Hadjimichael, Theo; Ohl, Raymond G.; Berrier, Joshua; Gum, Jeffery; Hayden, Joseph; Khreishi, Manal; McLean, Kyle; Redman, Kevin; Sullivan, Joseph; Wenzel, Greg;

An outline of tectonic, igneous, and metamorphic events in the Goshute-Toano Range between Silver Zone Pass and White Horse Pass, Elko County, Nevada; a history of superposed contractional and extensional deformation

USGS Publications Warehouse

Ketner, Keith Brindley; Day, Warren C.; Elrick, Maya; Vaag, Myra K.; Zimmerman, Robert A.; Snee, Lawrence W.; Saltus, Richard W.; Repetski, John E.; Wardlaw, Bruce R.; Taylor, Michael E.; Harris, Anita G.

1998-01-01

Seven kinds of fault-bounded tracts are described. One of the tracts provides a good example of Mesozoic contractional folding and faulting; six exemplify various aspects of Miocene extensional faulting. Massive landslide deposits resulting from Tertiary faulting are described. Mesozoic intrusive rocks and extensive exposures of Miocene volcanic rocks are described and dated. The age ranges of stratigraphic units were based on numerous conodont collections, and ages of igneous rocks were determined by argon/argon and fission-track methods. The geologic complexity of the Goshute-Toano Range provides opportunities for many additional productive structural studies.

Metrology for Trending Alignment of the James Webb Space Telescope Before and After Ambient Environmental Testing

NASA Technical Reports Server (NTRS)

Hadjimichael, Theo; Ohl, Raymond G.; Berrier, Joshua; Gum, Jeff; Hayden, Joseph; Khreishi, Manal; Mclean, Kyle; Redman, Kevin; Sullivan, Joseph; Wenzel, Greg;

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.

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.

Accurate de novo design of hyperstable constrained peptides

PubMed Central

Bhardwaj, Gaurav; Mulligan, Vikram Khipple; Bahl, Christopher D.; Gilmore, Jason M.; Harvey, Peta J.; Cheneval, Olivier; Buchko, Garry W.; Pulavarti, Surya V.S.R.K.; Kaas, Quentin; Eletsky, Alexander; Huang, Po-Ssu; Johnsen, William A.; Greisen, Per; Rocklin, Gabriel J.; Song, Yifan; Linsky, Thomas W.; Watkins, Andrew; Rettie, Stephen A.; Xu, Xianzhong; Carter, Lauren P.; Bonneau, Richard; Olson, James M.; Coutsias, Evangelos; Correnti, Colin E.; Szyperski, Thomas; Craik, David J.; Baker, David

2016-01-01

Summary Naturally occurring, pharmacologically active peptides constrained with covalent crosslinks generally have shapes evolved to fit precisely into binding pockets on their targets. Such peptides can have excellent pharmaceutical properties, combining the stability and tissue penetration of small molecule drugs with the specificity of much larger protein therapeutics. The ability to design constrained peptides with precisely specified tertiary structures would enable the design of shape-complementary inhibitors of arbitrary targets. Here we describe the development of computational methods for de novo design of conformationally-restricted peptides, and the use of these methods to design 15–50 residue disulfide-crosslinked and heterochiral N-C backbone-cyclized peptides. These peptides are exceptionally stable to thermal and chemical denaturation, and twelve experimentally-determined X-ray and NMR structures are nearly identical to the computational models. The computational design methods and stable scaffolds presented here provide the basis for development of a new generation of peptide-based drugs. PMID:27626386

The Effect of Nasoalveolar Molding on Nasal Airway Anatomy: A 9-Year Follow-up of Patients With Unilateral Cleft Lip and Palate.

PubMed

Massie, Jonathan P; Bruckman, Karl; Rifkin, William J; Runyan, Christopher M; Shetye, Pradip R; Grayson, Barry; Flores, Roberto L

2018-04-01

To determine the effects of nasoalveolar molding (NAM) on nasal airway architecture. Retrospective case-control study of patients with unilateral cleft lip treated with NAM vs without NAM. Tertiary referral center specializing in cleft and craniofacial care. Patients, Participants, and Interventions: Thirty-six patients with complete unilateral cleft lip and alveolus: 19 with NAM therapy and 17 without NAM therapy. Cone beam computed tomography (CBCT) scans were compared in multiple coronal sections and were evaluated for linear and angular septal deviation, inferior turbinate hypertrophy, and linear and 2-dimensional airway area. There were no significant differences in linear or angular septal deviation, inferior turbinate area, linear stenosis, or airway area between NAM- and non-NAM-treated patients. NAM effectively molds the external nasal cartilage and structures but may have limited effects on internal nasal structures.

Reconnaissance geologic map of the Loreto and part of the San Janier quadrangles, Baja California Sur, Mexico

USGS Publications Warehouse

McLean, Hugh

1988-01-01

The Loreto area of Baja California Sur, Mexico, contains a diverse association of igneous, sedimentary, and metasedimentary rocks exposed in the foothills and arroyos between the Sierra La Giganta and Gulf of California. The Loreto area was selected for this study to examine the possible relation of the marine rocks to the opening of the Gulf of California, and to determine the stratigraphic and structural relations between basement rocks composed of granitic and prebatholithic rocks and overlying Tertiary (mainly Miocene) sedimentary and volcanic rocks, and by a sequence of Pliocene marine and nonmarine sedimentary rocks. The Pliocene marine rocks lie in a structural depression informally called here, the Loreto embayment. This geologic map and report stem from a cooperative agreement between the U.S. Geological Survey and the Consejo de Recursos Minerales of Mexico that was initiated in 1982.

Crustal-scale geological and thermal models of the Beaufort-Mackenzie Basin, Arctic Canada

NASA Astrophysics Data System (ADS)

Sippel, Judith; Scheck-Wenderoth, Magdalena; Kröger, Karsten; Lewerenz, Björn

2010-05-01

The Beaufort-Mackenzie Basin is a petroliferous province in northwest Arctic Canada and one of the best-known segments of the Arctic Ocean margin due to decades of exploration. Our study is part of the programme MOM (Methane On the Move), which aims to quantify the methane contribution from natural petroleum systems to the atmosphere over geological times. Models reflecting the potential of a sedimentary basin to release methane require well-assessed boundary conditions such as the crustal structure and large-scale temperature variation. We focus on the crustal-scale thermal field of the Beaufort-Mackenzie Basin. This Basin has formed on a post-rift, continental margin which, during the Late Cretaceous and Tertiary, developed into the foreland of the North American Cordilleran foldbelt providing space for the accumulation of up to 16 km of foreland deposits. We present a 3D geological model which integrates the present topography, depth maps of Upper Cretaceous and Tertiary horizons (Kroeger et al., 2008, 2009), tops of formations derived from interpreted 2D reflection seismic lines and 284 boreholes (released by the National Energy Board of Canada), and the sequence stratigraphic framework established by previous studies (e.g. Dixon et al., 1996). To determine the position and geometry of the crust-mantle boundary, an isostatic calculation (Airýs model) is applied to the geological model. We present different crustal-scale models combining isostatic modelling, published deep reflection and refraction seismic lines (e.g. Stephenson et al., 1994; O'Leary et al., 1995), and calculations of the 3D conductive thermal field. References: Dixon, J., 1996. Geological Atlas of the Beaufort-Mackenzie Area, Geological Survey of Canada Miscellaneous Report, 59, Ottawa, 173 pp. Kroeger, K.F., Ondrak, R., di Primio, R. and Horsfield, B., 2008. A three-dimensional insight into the Mackenzie Basin (Canada): Implications for the thermal history and hydrocarbon generation potential of Tertiary deltaic sequences, AAPG Bulletin, 92(2): 225-247. Kroeger, K.F., di Primio, R. and Horsfield, B., (2009). Hydrocarbon flow modeling in complex structures (Mackenzie Basin, Canada), AAPG Bulletin, 93(9): 1-25. O'Leary, D.M., Ellis, R.M., Stephenson, R.A., Lane, L.S. and Zelt, C.A., 1995. Crustal structure of the northern Yukon and Mackenzie Delta, northwestern Canada, Journal of Geophysical Research 100(B7): 9905-9920. Stephenson, R.A., Coflin, K.C., Lane, L.S. and Dietrich, J.R., 1994. Crustal structure and tectonics of the southeastern Beaufort Sea continental margin, Tectonics, 13(2): 389-400.

Six-month outcome in unstable angina patients without previous myocardial infarction according to the use of tertiary cardiologic resources. RESCATE Investigators. Recursos Empleados en el Síndrome Coronario Agudo y Tiempos de Espera.

PubMed

Lupón, J; Valle, V; Marrugat, J; Elosua, R; Serés, L; Pavesi, M; Freixa, R; Sanz, G; Masiá, R; Molina, L; Sala, J; Serra, J

1999-12-01

The study assessed whether varying accessibility of patients with unstable angina (UA) to coronary angiography and revascularization determined differing usages and outcomes. The appropriate use rate of coronary angiography and revascularization procedures in UA remains to be established. A total of 791 consecutive patients with UA without previous acute myocardial infarction (AMI) admitted to four reference teaching hospitals (one with tertiary facilities) were followed for six months. End points were six-month mortality and readmission for AMI, UA, heart failure, or severe ventricular arrhythmias. Patients admitted to the tertiary hospital were 3.27 (95% confidence interval [CI] 2.32 to 4.62) times more likely to undergo coronary angiography after adjustment for comorbidity and severity than were those admitted to nontertiary facilities (overall six-month use rates 70.1% and 48.3%, respectively). Revascularization procedures were performed in 36.2% of patients in the tertiary hospital and 24.6% in the others (p = 0.0007); adjusted relative risk (RR) 2.37 (95% CI 1.55 to 3.63). Median delay for urgent coronary angiography was shorter in the tertiary hospital (24 h vs. 4 days, p < 0.0002). Six-month mortality and readmission rates were similar in tertiary and nontertiary hospitals: 3.9% versus 5.3% and 16.9% versus 21.2%, respectively. Adjusted RR of death or readmission for the nontertiary hospitals was 1.23 (95% CI 0.57 to 2.67). The use of coronary angiography and revascularization procedures in UA patients with no previous AMI is higher in tertiary than in nontertiary hospitals, but the more selective use of these procedures in nontertiary centers does not imply worse outcome.

Impact of Eating Attitude and Impairment of Physical Quality of Life Between Tertiary Clinic and Primary Clinic Functional Dyspepsia Outpatients in Japan

PubMed Central

Shimpuku, Mayumi; Futagami, Seiji; Tajima, Natsuki; Yamawaki, Hiroshi; Maruki, Yuuta; Kodaka, Yasuhiro; Nagoya, Hiroyuki; Gudis, Katya; Kawagoe, Tetsuro; Sakamoto, Choitsu

2014-01-01

Background/Aims There is no available data on factors associated with healthcare-seeking behavior for functional dyspepsia (FD) symptoms at either tertiary or primary clinics in Japan. Therefore, we aimed to compare clinical symptoms and life styles such as sleep disorders and eating attitude in FD patients visiting general practitioners at primary clinics with those consulting gastroenterologists at tertiary clinics to clarify healthcare-seeking patterns in Japanese patients. Methods Fifty-one FD outpatients in a tertiary clinic (college hospital), 50 FD outpatients visiting primary clinics and 50 healthy volunteers were enrolled. Clinical symptoms, quality of life, sleep disorders, eating attitude and anxiety were estimated using the Gastrointestinal Symptom Rating Scale (GSRS), Social Functioning-8 (SF-8) test, Pittsburg Sleep Quality Index (PSQI) test and State-Trait Anxiety Inventory (STAI) for FD outpatients and healthy volunteers. Results FD outpatients exhibited higher mean scores of GSRS than healthy volunteers. The SF-8 physical component summary scores in the tertiary clinic group were significantly lower than those in the primary clinic group. GSRS scores were significantly (P < 0.001, P = 0.002) associated with global PSQI scores in FD outpatients as well as with STAI-trait scores (P = 0.006, P = 0.001) compared to healthy volunteers. The frequency of eating between meals in the primary clinic group was significantly (P < 0.05) higher than that in the tertiary clinic group. Conclusions It may be important for clarification of healthcare-seeking behavior to determine the difference in both impairment of physical quality of life and eating attitudes between tertiary clinic and primary clinic FD outpatients in Japan. PMID:25273121

Location and age of foraminifer samples collected by Chevron Petroleum geologists in California

USGS Publications Warehouse

Brabb, Earl E.; Parker, John M.

2003-01-01

Most of the geologic maps published for parts of central California in the past century have been made without the benefit of ages from microfossils. The ages of Jurassic, Cretaceous and Tertiary rocks in the mostly poorly exposed and structurally complex sedimentary rocks represented in the Coast Ranges are critical in determining stratigraphic succession or lack of it, and in determining whether the juxtaposition of similar appearing but different age formations means that a fault is present. Since the 1940's, at least, oil company geologists have used microfossils to assist them in geologic mapping and in determining the environments of deposition of the sedimentary rocks containing them. This information had been so confidential that even the names of species were coded by some paleontologists to prevent disclosure. In the past 20 years, however, the attitude of petroleum companies about this information has changed, and many of the formerly confidential materials and reports are now available. We report here on an estimated 50,000 Chevron foraminifer samples from surface localities in more than 600 U.S. Geological Survey 7.5' quadrangles in California. Ages are provided for more than 27,000 of these samples which have been donated by Chevron, along with locality maps, paleontology reports, and other data, to the California Academy of Sciences. To our knowledge, this collection is the largest ever released to the public by a petroleum company for the West Coast. The information from the slides can be used to update geologic maps prepared without the benefit of microfossils, to study foraminifers of Jurassic, Cretaceous and Tertiary age collected from a variety of geologic environments, to analyze the depth and temperature of ocean water covering parts of California during these periods, and for solving nomenclature and other scientific problems.

A combination of feature extraction methods with an ensemble of different classifiers for protein structural class prediction problem.

PubMed

Dehzangi, Abdollah; Paliwal, Kuldip; Sharma, Alok; Dehzangi, Omid; Sattar, Abdul

2013-01-01

Better understanding of structural class of a given protein reveals important information about its overall folding type and its domain. It can also be directly used to provide critical information on general tertiary structure of a protein which has a profound impact on protein function determination and drug design. Despite tremendous enhancements made by pattern recognition-based approaches to solve this problem, it still remains as an unsolved issue for bioinformatics that demands more attention and exploration. In this study, we propose a novel feature extraction model that incorporates physicochemical and evolutionary-based information simultaneously. We also propose overlapped segmented distribution and autocorrelation-based feature extraction methods to provide more local and global discriminatory information. The proposed feature extraction methods are explored for 15 most promising attributes that are selected from a wide range of physicochemical-based attributes. Finally, by applying an ensemble of different classifiers namely, Adaboost.M1, LogitBoost, naive Bayes, multilayer perceptron (MLP), and support vector machine (SVM) we show enhancement of the protein structural class prediction accuracy for four popular benchmarks.

Map showing contours on top of the upper Cretaceous Mowry Shale, Powder River basin, Wyoming and Montana

USGS Publications Warehouse

Crysdale, B.L.

1991-01-01

This map is one in a series of U.S. Geological Survey Miscellaneous Field Studies (MF) maps showing computer-generated structure contours, isopachs, and cross sections of selected formations in the Powder River basin, Wyoming and Montana. The map and cross sections were constructed from information stored in a U.S. Geological Survey Evolution of Sedimentary Basins data base. This data base contains picks of geologic formation and (or) unit tops and bases determined from electric resistivity and gamma-ray logs of 8,592 wells penetrating Tertiary and older rocks in the Powder River basin. Well completion cards (scout tickets) were reviewed and compared with copies of all logs, and formation or unit contacts determined by N. M. Denson, D.L. Macke, R. R. Schumann and others. This isopach map is based on information from 4,926 of these wells that penetrate the Minnelusa Formation and equivalents.

Enthalpy-Driven RNA Folding: Single-Molecule Thermodynamics of Tetraloop–Receptor Tertiary Interaction†

PubMed Central

Fiore, Julie L.; Kraemer, Benedikt; Koberling, Felix; Edmann, Rainer; Nesbitt, David J.

2010-01-01

RNA folding thermodynamics are crucial for structure prediction, which requires characterization of both enthalpic and entropic contributions of tertiary motifs to conformational stability. We explore the temperature dependence of RNA folding due to the ubiquitous GAAA tetraloop–receptor docking interaction, exploiting immobilized and freely diffusing single-molecule fluorescence resonance energy transfer (smFRET) methods. The equilibrium constant for intramolecular docking is obtained as a function of temperature (T = 21–47 °C), from which a van’t Hoff analysis yields the enthalpy (ΔH°) and entropy (ΔS°) of docking. Tetraloop–receptor docking is significantly exothermic and entropically unfavorable in 1 mM MgCl2 and 100 mM NaCl, with excellent agreement between immobilized (ΔH° = −17.4 ± 1.6 kcal/mol, and ΔS° = −56.2 ± 5.4 cal mol−1 K−1) and freely diffusing (ΔH° = −17.2 ± 1.6 kcal/mol, and ΔS° = −55.9 ± 5.2 cal mol−1 K−1) species. Kinetic heterogeneity in the tetraloop–receptor construct is unaffected over the temperature range investigated, indicating a large energy barrier for interconversion between the actively docking and nondocking subpopulations. Formation of the tetraloop–receptor interaction can account for ~60% of the ΔH° and ΔS° of P4–P6 domain folding in the Tetrahymena ribozyme, suggesting that it may act as a thermodynamic clamp for the domain. Comparison of the isolated tetraloop–receptor and other tertiary folding thermodynamics supports a theme that enthalpy- versus entropy-driven folding is determined by the number of hydrogen bonding and base stacking interactions. PMID:19186984

Binding of manganese(II) to a tertiary stabilized hammerhead ribozyme as studied by electron paramagnetic resonance spectroscopy

PubMed Central

KISSELEVA, NATALIA; KHVOROVA, ANASTASIA; WESTHOF, ERIC; SCHIEMANN, OLAV

2005-01-01

Electron paramagnetic resonance (EPR) spectroscopy is used to study the binding of MnII ions to a tertiary stabilized hammer-head ribozyme (tsHHRz) and to compare it with the binding to the minimal hammerhead ribozyme (mHHRz). Continuous wave EPR measurements show that the tsHHRz possesses a single high-affinity MnII binding site with a KD of ≤10 nM at an NaCl concentration of 0.1 M. This dissociation constant is at least two orders of magnitude smaller than the KD determined previously for the single high-affinity MnII site in the mHHRz. In addition, whereas the high-affinity MnII is displaced from the mHHRz upon binding of the aminoglycoside antibiotic neomycin B, it is not from the tsHHRz. Despite these pronounced differences in binding, a comparison between the electron spin echo envelope modulation and hyperfine sublevel correlation spectra of the minimal and tertiary stabilized HHRz demonstrates that the structure of both binding sites is very similar. This suggests that the MnII is located in both ribozymes between the bases A9 and G10.1 of the sheared G · A tandem base pair, as shown previously and in detail for the mHHRz. Thus, the much stronger MnII binding in the tsHHRz is attributed to the interaction between the two external loops, which locks in the RNA fold, trapping the MnII in the tightly bound conformation, whereas the absence of long-range loop–loop interactions in the mHHRz leads to more dynamical and open conformations, decreasing MnII binding. PMID:15611296

Blast biology: a study of the primary and tertiary effects of blast in open underground protective shelters. Project 33. 1 of Operation Plumbbob

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

Ricmond, D.R.; Taborelli, R.V.; Bowen, I.G.

1959-02-01

Dogs, pigs, rabbits, guinea pigs, and mice were exposed to nuclear detonations in two open underground partitioned shelters. The shelters were of similar construction, and each was exposed to separate detonations. Each inner chamber filled through its own orifice; thus four separate pressure environments were obtained. An aerodynamic mound was placed over the escape hatch of each structure to determine its effect on the pressure-curve shape inside the chamber. In one test a sieve plate bolted across the top of the mound was evaluated. Wind protective baffles of solid plate and of heavy wire screen were installed in the sheltersmore » to compare primary and tertiary blast effects on dogs. The shelters also contained static and dynamic pressure gages, radiation detectors, telemetering devices, and, in one test, air-temperature measuring instruments, dust-collecting trays, and eight pigs for the biological assessment of thermal effects. One dog was severely injured from tertiary blast effects associated with a maximal dynamic pressure (Q) of 10.5 psi, and one was undamaged with a maximal Q of 2 psi. Primary blast effects resulting from peak overpressures of 30.3, 25.5, 9.5, and 4.1 psi were minimal. The mortality was 19% of the mice exposed to a peak pressure of 30.3 psi and 5 and 3% of the guinea pigs and mice exposed to a peak pressure of 25.5 psi. Many of the rabbits, guinea pigs, and mice sustained slight lung hemorrhages at maximum pressues of 25.5 and 30.3 psi. Eardrum perforation data for all species, except mice, were recorded. Following shot 2, thermal effects were noted. Animals of the groups saved for observation have died from ionizing-radiation effects.« less

BLAST BIOLOGY--A STUDY OF THE PRIMARY AND TERTIARY EFFECTS OF BLAST IN OPEN UNDERGROUND PROTECTIVE SHELTERS

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

Ricmond, D.R.; Taborelli, R.V.; Bowen, I.G.

1959-02-01

Dogs, pigs, rabbits, guinea pigs, and mice were exposed to nuclear detonatiors in two open underground pantitioned shelters. The shelters were of similar constructions and each was exposed to separate detonations. Each inner chamber filled through its own orifice; thus four separate pressure enviromments were obtained. An aerodynamic mound was placed over the escape hatch of each structure to determine its effect on the pressurecurve shape inside the chamber. In one test a sieve plate bolted across the top of the mound was evaluated. Wind protective baffles of solid plate and of heavy wire screen were installed in the sheltersmore » to compare primary and tertiary blast effects on dogs. The shelters also contained static and dynamic pressure gages, radiation detectors, telemetering devices, and, in one test, air-temperature measuring instruments, dustcollecting trays, and eight pigs for the biological assessment of thermal effects. One dog was severely injured from tertiary blast effects associated with a maximal dynamic pressure (Q) of 10.5 psi, and one was undamaged with a maximal Q of 2 psi. Primary blast effects resulting from peak overpressures of 30.3, 25.5, 9.5. and 4.1 psi were minimal. The mortality was 19 per cent of the mice exposed to a peak pressure of 30.3 psi and 5 and 3 per cent of the guinea pigs and mice exposed to a peak pressure of 25.5 psi. Many of the rabbits, guinea pigs, and mice sustained slight lung hemorrhages at maximum pressures of 25.5 and 30.3 psi. Eardrum perforation data for all species, except mice, were recorded. Following shot 2, thermal effects were noted. Animals of the groups saved for observation have died from ionizing-radiation effects. (auth)« less

BASIN ANALYSIS AND PETROLEUM SYSTEM CHARACTERIZATION AND MODELING, INTERIOR SALT BASINS, CENTRAL AND EASTERN GULF OF MEXICO

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

Ernest A. Mancini; Donald A. Goddard; Ronald K. Zimmerman

2005-05-10

The principal research effort for Year 2 of the project has been data compilation and the determination of the burial and thermal maturation histories of the North Louisiana Salt Basin and basin modeling and petroleum system identification. In the first nine (9) months of Year 2, the research focus was on the determination of the burial and thermal maturation histories, and during the remainder of the year the emphasis has basin modeling and petroleum system identification. Existing information on the North Louisiana Salt Basin has been evaluated, an electronic database has been developed, regional cross sections have been prepared, structuremore » and isopach maps have been constructed, and burial history, thermal maturation history and hydrocarbon expulsion profiles have been prepared. Seismic data, cross sections, subsurface maps and related profiles have been used in evaluating the tectonic, depositional, burial and thermal maturation histories of the basin. Oil and gas reservoirs have been found to be associated with salt-supported anticlinal and domal features (salt pillows, turtle structures and piercement domes); with normal faulting associated with the northern basin margin and listric down-to-the-basin faults (state-line fault complex) and faulted salt features; and with combination structural and stratigraphic features (Sabine and Monroe Uplifts) and monoclinal features with lithologic variations. Petroleum reservoirs are mainly Upper Jurassic and Lower Cretaceous fluvial-deltaic sandstone facies and Lower Cretaceous and Upper Cretaceous shoreline, marine bar and shallow shelf sandstone facies. Cretaceous unconformities significantly contribute to the hydrocarbon trapping mechanism capacity in the North Louisiana Salt Basin. The chief petroleum source rock in this basin is Upper Jurassic Smackover lime mudstone beds. The generation of hydrocarbons from Smackover lime mudstone was initiated during the Early Cretaceous and continued into the Tertiary. Hydrocarbon expulsion commenced during the Early Cretaceous and continued into the Tertiary with peak expulsion occurring mainly during the Late Cretaceous.« less

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

Quantitative Protein Topography Analysis and High-Resolution Structure Prediction Using Hydroxyl Radical Labeling and Tandem-Ion Mass Spectrometry (MS)*

PubMed Central

Kaur, Parminder; Kiselar, Janna; Yang, Sichun; Chance, Mark R.

2015-01-01

Hydroxyl radical footprinting based MS for protein structure assessment has the goal of understanding ligand induced conformational changes and macromolecular interactions, for example, protein tertiary and quaternary structure, but the structural resolution provided by typical peptide-level quantification is limiting. In this work, we present experimental strategies using tandem-MS fragmentation to increase the spatial resolution of the technique to the single residue level to provide a high precision tool for molecular biophysics research. Overall, in this study we demonstrated an eightfold increase in structural resolution compared with peptide level assessments. In addition, to provide a quantitative analysis of residue based solvent accessibility and protein topography as a basis for high-resolution structure prediction; we illustrate strategies of data transformation using the relative reactivity of side chains as a normalization strategy and predict side-chain surface area from the footprinting data. We tested the methods by examination of Ca+2-calmodulin showing highly significant correlations between surface area and side-chain contact predictions for individual side chains and the crystal structure. Tandem ion based hydroxyl radical footprinting-MS provides quantitative high-resolution protein topology information in solution that can fill existing gaps in structure determination for large proteins and macromolecular complexes. PMID:25687570

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.

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

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.

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.

Radial Velocities of 41 Kepler Eclipsing Binaries

NASA Astrophysics Data System (ADS)

Matson, Rachel A.; Gies, Douglas R.; Guo, Zhao; Williams, Stephen J.

2017-12-01

Eclipsing binaries are vital for directly determining stellar parameters without reliance on models or scaling relations. Spectroscopically derived parameters of detached and semi-detached binaries allow us to determine component masses that can inform theories of stellar and binary evolution. Here we present moderate resolution ground-based spectra of stars in close binary systems with and without (detected) tertiary companions observed by NASA’s Kepler mission and analyzed for eclipse timing variations. We obtain radial velocities and spectroscopic orbits for five single-lined and 35 double-lined systems, and confirm one false positive eclipsing binary. For the double-lined spectroscopic binaries, we also determine individual component masses and examine the mass ratio {M}2/{M}1 distribution, which is dominated by binaries with like-mass pairs and semi-detached classical Algol systems that have undergone mass transfer. Finally, we constrain the mass of the tertiary component for five double-lined binaries with previously detected companions.

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

A Deep Learning Network Approach to ab initio Protein Secondary Structure Prediction

PubMed Central

Spencer, Matt; Eickholt, Jesse; Cheng, Jianlin

2014-01-01

Ab initio protein secondary structure (SS) predictions are utilized to generate tertiary structure predictions, which are increasingly demanded due to the rapid discovery of proteins. Although recent developments have slightly exceeded previous methods of SS prediction, accuracy has stagnated around 80% and many wonder if prediction cannot be advanced beyond this ceiling. Disciplines that have traditionally employed neural networks are experimenting with novel deep learning techniques in attempts to stimulate progress. Since neural networks have historically played an important role in SS prediction, we wanted to determine whether deep learning could contribute to the advancement of this field as well. We developed an SS predictor that makes use of the position-specific scoring matrix generated by PSI-BLAST and deep learning network architectures, which we call DNSS. Graphical processing units and CUDA software optimize the deep network architecture and efficiently train the deep networks. Optimal parameters for the training process were determined, and a workflow comprising three separately trained deep networks was constructed in order to make refined predictions. This deep learning network approach was used to predict SS for a fully independent test data set of 198 proteins, achieving a Q3 accuracy of 80.7% and a Sov accuracy of 74.2%. PMID:25750595

A Deep Learning Network Approach to ab initio Protein Secondary Structure Prediction.

PubMed

Spencer, Matt; Eickholt, Jesse; Jianlin Cheng

2015-01-01

Ab initio protein secondary structure (SS) predictions are utilized to generate tertiary structure predictions, which are increasingly demanded due to the rapid discovery of proteins. Although recent developments have slightly exceeded previous methods of SS prediction, accuracy has stagnated around 80 percent and many wonder if prediction cannot be advanced beyond this ceiling. Disciplines that have traditionally employed neural networks are experimenting with novel deep learning techniques in attempts to stimulate progress. Since neural networks have historically played an important role in SS prediction, we wanted to determine whether deep learning could contribute to the advancement of this field as well. We developed an SS predictor that makes use of the position-specific scoring matrix generated by PSI-BLAST and deep learning network architectures, which we call DNSS. Graphical processing units and CUDA software optimize the deep network architecture and efficiently train the deep networks. Optimal parameters for the training process were determined, and a workflow comprising three separately trained deep networks was constructed in order to make refined predictions. This deep learning network approach was used to predict SS for a fully independent test dataset of 198 proteins, achieving a Q3 accuracy of 80.7 percent and a Sov accuracy of 74.2 percent.

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.

The use of team-based, guided inquiry learning to overcome educational disadvantages in learning human physiology: a structural equation model.

PubMed

Rathner, Joseph A; Byrne, Graeme

2014-09-01

The study of human bioscience is viewed as a crucial curriculum in allied health. Nevertheless, bioscience (and particularly physiology) is notoriously difficult for undergraduates, particularly academically disadvantaged students. So endemic are the high failure rates (particularly in nursing) that it has come to be known as "the human bioscience problem." In the present report, we describe the outcomes for individual success in studying first-year human physiology in a subject that emphasises team-based active learning as the major pedagogy for mastering subject learning outcomes. Structural equation modeling was used to develop a model of the impact team learning had on individual performance. Modeling was consistent with the idea that students with similar academic abilities (as determined by tertiary entrance rank) were advantaged (scored higher on individual assessment items) by working in strong teams (teams that scored higher in team-based assessments). Analysis of covariance revealed that students who studied the subject with active learning as the major mode of learning activities outperformed students who studied the subject using the traditional didactic teaching format (lectures and tutorials, P = 0.000). After adjustment for tertiary entrance rank (via analysis of covariance) on two individual tests (the final exam and a late-semester in-class test), individual student grades improved by 8% (95% confidence interval: 6-10%) and 12% (95% confidence interval: 10-14%) when students engaged in team-based active learning. These data quantitatively support the notion that weaker students working in strong teams can overcome their educational disadvantages. Copyright © 2014 The American Physiological Society.

The use of team-based, guided inquiry learning to overcome educational disadvantages in learning human physiology: a structural equation model

PubMed Central

Byrne, Graeme

2014-01-01

The study of human bioscience is viewed as a crucial curriculum in allied health. Nevertheless, bioscience (and particularly physiology) is notoriously difficult for undergraduates, particularly academically disadvantaged students. So endemic are the high failure rates (particularly in nursing) that it has come to be known as “the human bioscience problem.” In the present report, we describe the outcomes for individual success in studying first-year human physiology in a subject that emphasises team-based active learning as the major pedagogy for mastering subject learning outcomes. Structural equation modeling was used to develop a model of the impact team learning had on individual performance. Modeling was consistent with the idea that students with similar academic abilities (as determined by tertiary entrance rank) were advantaged (scored higher on individual assessment items) by working in strong teams (teams that scored higher in team-based assessments). Analysis of covariance revealed that students who studied the subject with active learning as the major mode of learning activities outperformed students who studied the subject using the traditional didactic teaching format (lectures and tutorials, P = 0.000). After adjustment for tertiary entrance rank (via analysis of covariance) on two individual tests (the final exam and a late-semester in-class test), individual student grades improved by 8% (95% confidence interval: 6–10%) and 12% (95% confidence interval: 10–14%) when students engaged in team-based active learning. These data quantitatively support the notion that weaker students working in strong teams can overcome their educational disadvantages. PMID:25179611

Turning limited experimental information into 3D models of RNA.

PubMed

Flores, Samuel Coulbourn; Altman, Russ B

2010-09-01

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

Solution structure of an ATP-binding RNA aptamer reveals a novel fold.

PubMed Central

Dieckmann, T; Suzuki, E; Nakamura, G K; Feigon, J

1996-01-01

In vitro selection has been used to isolate several RNA aptamers that bind specifically to biological cofactors. A well-characterized example in the ATP-binding RNA aptamer family, which contains a conserved 11-base loop opposite a bulged G and flanked by regions of double-stranded RNA. The nucleotides in the consensus sequence provide a binding pocket for ATP (or AMP), which binds with a Kd in the micromolar range. Here we present the three-dimensional solution structure of a 36-nucleotide ATP-binding RNA aptamer complexed with AMP, determined from NMR-derived distance and dihedral angle restraints. The conserved loop and bulged G form a novel compact, folded structure around the AMP. The backbone tracing of the loop nucleotides can be described by a Greek zeta (zeta). Consecutive loop nucleotides G, A, A form a U-turn at the bottom of the zeta, and interact with the AMP to form a structure similar to a GNRA tetraloop, with AMP standing in for the final A. Two asymmetric G. G base pairs close the stems flanking the internal loop. Mutated aptamers support the existence of the tertiary interactions within the consensus nucleotides and with the AMP found in the calculated structures. PMID:8756406

Validated near-atomic resolution structure of bacteriophage epsilon15 derived from cryo-EM and modeling

PubMed Central

Baker, Matthew L.; Hryc, Corey F.; Zhang, Qinfen; Wu, Weimin; Jakana, Joanita; Haase-Pettingell, Cameron; Afonine, Pavel V.; Adams, Paul D.; King, Jonathan A.; Jiang, Wen; Chiu, Wah

2013-01-01

High-resolution structures of viruses have made important contributions to modern structural biology. Bacteriophages, the most diverse and abundant organisms on earth, replicate and infect all bacteria and archaea, making them excellent potential alternatives to antibiotics and therapies for multidrug-resistant bacteria. Here, we improved upon our previous electron cryomicroscopy structure of Salmonella bacteriophage epsilon15, achieving a resolution sufficient to determine the tertiary structures of both gp7 and gp10 protein subunits that form the T = 7 icosahedral lattice. This study utilizes recently established best practice for near-atomic to high-resolution (3–5 Å) electron cryomicroscopy data evaluation. The resolution and reliability of the density map were cross-validated by multiple reconstructions from truly independent data sets, whereas the models of the individual protein subunits were validated adopting the best practices from X-ray crystallography. Some sidechain densities are clearly resolved and show the subunit–subunit interactions within and across the capsomeres that are required to stabilize the virus. The presence of the canonical phage and jellyroll viral protein folds, gp7 and gp10, respectively, in the same virus suggests that epsilon15 may have emerged more recently relative to other bacteriophages. PMID:23840063

Structural computational modeling of RNA aptamers.

PubMed

Xu, Xiaojun; Dickey, David D; Chen, Shi-Jie; Giangrande, Paloma H

2016-07-01

RNA aptamers represent an emerging class of biologics that can be easily adapted for personalized and precision medicine. Several therapeutic aptamers with desirable binding and functional properties have been developed and evaluated in preclinical studies over the past 25years. However, for the majority of these aptamers, their clinical potential has yet to be realized. A significant hurdle to the clinical adoption of this novel class of biologicals is the limited information on their secondary and tertiary structure. Knowledge of the RNA's structure would greatly facilitate and expedite the post-selection optimization steps required for translation, including truncation (to reduce costs of manufacturing), chemical modification (to enhance stability and improve safety) and chemical conjugation (to improve drug properties for combinatorial therapy). Here we describe a structural computational modeling methodology that when coupled to a standard functional assay, can be used to determine key sequence and structural motifs of an RNA aptamer. We applied this methodology to enable the truncation of an aptamer to prostate specific membrane antigen (PSMA) with great potential for targeted therapy that had failed previous truncation attempts. This methodology can be easily applied to optimize other aptamers with therapeutic potential. Copyright © 2016. Published by Elsevier Inc.

What are we telling the parents of extremely preterm babies?

PubMed

Boland, Rosemarie Anne; Davis, Peter Graham; Dawson, Jennifer Anne; Doyle, Lex William

2016-06-01

Parent counselling and decision-making regarding the management of preterm labour and birth are influenced by information provided by healthcare professionals regarding potential infant outcomes. The aim of this study was to determine whether perinatal healthcare providers had accurate perceptions of survival and major neurosensory disability rates of very preterm infants born in non-tertiary hospitals ('outborn') and tertiary perinatal centres ('inborn'). A web-based survey was distributed to midwives, nurses, obstetricians and neonatologists working in non-tertiary and tertiary maternity hospitals, and the perinatal/neonatal emergency transport services in Victoria, Australia. Estimates of survival rates at 24 and 28-weeks' gestation were compared with actual survival rates of a population-based cohort of 24 and 28-weeks' gestation infants, born free of lethal anomalies in Victoria in 2001-2009. Estimates of major neurosensory disability rates in 24 and 28-week survivors were compared with actual disability rates in 24 and 28-week children born in Victoria averaged over three eras: 1991-1992, 1997 and 2005. Response rates varied as follows: 83% of non-tertiary midwives, 4% of obstetricians, 55% of tertiary centre staff and 68% of transport team staff responded (total of 30%). Overall, respondents underestimated survival and overestimated major neurosensory disability rates in both outborn and inborn 24 and 28-week infants. Outborn infants were perceived to have much worse prospects for survival and for survival with major disability compared with inborn peers. Many clinicians overestimated rates of adverse outcomes. These clinicians may be misinforming parents about their child's potential for a favourable outcome. © 2016 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Saturated amine oxides: Part 8. Hydroacridines: Part 27. Effects of N-oxidation and of N-quaternization on the 15N NMR chemical shifts of N-methylpiperidine-derived mono-, bi-, and tricycloaliphatic tertiary amines.

PubMed

Potmischil, Francisc; Duddeck, Helmut; Nicolescu, Alina; Deleanu, Calin

2007-03-01

The (15)N chemical shifts of 13 N-methylpiperidine-derived mono-, bi- and tricycloaliphatic tertiary amines, their methiodides and their N-epimeric pairs of N-oxides were measured, and the contributions of specific structural parameters to the chemical shifts were determined by multilinear regression analysis. Within the examined compounds, the effects of N-oxidation upon the (15)N chemical shifts of the amines vary from +56 ppm to +90 ppm (deshielding), of which approx. +67.7 ppm is due to the inductive effect of the incoming N(+)--O(-) oxygen atom, whereas the rest is due to the additive shift effects of the various C-alkyl substituents of the piperidine ring. The effects of quaternization vary from -3.1 ppm to +29.3 ppm, of which approx. +8.9 ppm is due to the inductive effect of the incoming N(+)--CH(3) methyl group, and the rest is due to the additive shift effects of the various C-alkyl substituents of the piperidine ring. The shift effects of the C-alkyl substituents in the amines, the N-oxides and the methiodides are discussed. Copyright (c) 2007 John Wiley & Sons, Ltd.

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

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.

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

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.

Differences in the catalytic mechanisms of mesophilic and thermophilic indole-3-glycerol phosphate synthase enzymes at their adaptive temperatures.

PubMed

Zaccardi, Margot J; Mannweiler, Olga; Boehr, David D

2012-02-10

Thermophilic enzymes tend to be less catalytically-active at lower temperatures relative to their mesophilic counterparts, despite having very similar crystal structures. An often cited hypothesis for this general observation is that thermostable enzymes have evolved a more rigid tertiary structure in order to cope with their more extreme, natural environment, but they are also less flexible at lower temperatures, leading to their lower catalytic activity under mesophilic conditions. An alternative hypothesis, however, is that complementary thermophilic-mesophilic enzyme pairs simply operate through different evolutionary-optimized catalytic mechanisms. In this communication, we present evidence that while the steps of the catalytic mechanisms for mesophilic and thermophilic indole-3-glycerol phosphate synthase (IGPS) enzymes are fundamentally similar, the identity of the rate-determining step changes as a function of temperature. Our findings indicate that while product release is rate-determining at 25°C for thermophilic IGPS, near its adaptive temperature (75°C), a proton transfer event, involving a general acid, becomes rate-determining. The rate-determining steps for thermophilic and mesophilic IGPS enzymes are also different at their respective, adaptive temperatures with the mesophilic IGPS-catalyzed reaction being rate-limited before irreversible CO2 release, and the thermophilic IGPS-catalyzed reaction being rate limited afterwards. Copyright © 2012 Elsevier Inc. All rights reserved.

Relationships between IgE/IgG4 Epitopes, Structure and Function in Anisakis simplex Ani s 5, a Member of the SXP/RAL-2 Protein Family

PubMed Central

García-Mayoral, María Flor; Treviño, Miguel Angel; Pérez-Piñar, Teresa; Caballero, María Luisa; Knaute, Tobias; Umpierrez, Ana

2014-01-01

Background Anisakiasis is a re-emerging global disease caused by consumption of raw or lightly cooked fish contaminated with L3 Anisakis larvae. This zoonotic disease is characterized by severe gastrointestinal and/or allergic symptoms which may misdiagnosed as appendicitis, gastric ulcer or other food allergies. The Anisakis allergen Ani s 5 is a protein belonging to the SXP/RAL-2 family; it is detected exclusively in nematodes. Previous studies showed that SXP/RAL-2 proteins are active antigens; however, their structure and function remain unknown. The aim of this study was to elucidate the three-dimensional structure of Ani s 5 and its main IgE and IgG4 binding regions. Methodology/Principal Findings The tertiary structure of recombinant Ani s 5 in solution was solved by nuclear magnetic resonance. Mg2+, but not Ca2+, binding was determined by band shift using SDS-PAGE. IgE and IgG4 epitopes were elucidated by microarray immunoassay and SPOTs membranes using sera from nine Anisakis allergic patients. The tertiary structure of Ani s 5 is composed of six alpha helices (H), with a Calmodulin like fold. H3 is a long, central helix that organizes the structure, with H1 and H2 packing at its N-terminus and H4 and H5 packing at its C-terminus. The orientation of H6 is undefined. Regarding epitopes recognized by IgE and IgG4 immunoglobulins, the same eleven peptides derived from Ani s 5 were bound by both IgE and IgG4. Peptides 14 (L40-K59), 26 (A76-A95) and 35 (I103-D122) were recognized by three out of nine sera. Conclusions/Significance This is the first reported 3D structure of an Anisakis allergen. Magnesium ion binding and structural resemblance to Calmodulin, suggest some putative functions for SXP/RAL-2 proteins. Furthermore, the IgE/IgG4 binding regions of Ani s 5 were identified as segments localized on its surface. These data will contribute towards a better understanding of the interactions that occur between immunoglobulins and allergens and, in turn, facilitate the design of novel diagnostic tests and immunotherapeutic strategies. PMID:24603892

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

Manjasetty, Babu A.; Halavaty, Andrei S.; Luan, Chi-Hao

Multidrug transcription regulator AcrR from Salmonella enterica subsp. enterica serovar Typhimurium str. LT2 belongs to the tetracycline repressor family, one of the largest groups of bacterial transcription factors. The crystal structure of dimeric AcrR was determined and refined to 1.56 Å resolution. The tertiary and quaternary structures of AcrR are similar to those of its homologs. The multidrug binding site was identified based on structural alignment with homologous proteins and has a di(hydroxyethyl)ether molecule bound. Residues from helices a4 and a7 shape the entry into this binding site. The structure of AcrR reveals that the extended helical conformation of helixmore » a4 is stabilized by the hydrogen bond between Glu67 (helix a4) and Gln130 (helix a7). Based on the structural comparison with the closest homolog structure, the Escherichia coli AcrR, we propose that this hydrogen bond is responsible for control of the loop-to-helix transition within helix a4. This local conformational switch of helix a4 may be a key step in accessing the multidrug binding site and securing ligands at the binding site. Solution smallmolecule binding studies suggest that AcrR binds ligands with their core chemical structure resembling the tetracyclic ring of cholesterol.« less

Does gynecologic malignancy predict likelihood of a tertiary palliative care unit hospital admission? A comparison of local, provincial and national death rates.

PubMed

Pilkey, Jana; Demers, Chantale; Chochinov, Harvey; Venkatesan, Nithya

2012-12-01

The purpose of this study was to determine whether the presence of gynecologic malignancies predicts the likelihood of a tertiary palliative care unit hospital admission. In this study, patients admitted to a specialized tertiary palliative care unit (TPCU) with gynecologic malignancies were compared to national and provincial death rates to determine if gynecologic malignancy predicts admission, and subsequent death, in a TPCU. Eighty-two gynecologic cancer patients were admitted to our TPCU over the 5- year study period. Out of all cancer deaths in the TPCU, death from ovarian cancer was 3.7% compared with 2.4% (p = 0.0068) of all cancer deaths in Manitoba and 2.3% (p = 0.0043) of all cancer deaths in Canada. Cervical cancer accounted for 1.7% of all our patients deaths compared with 0.7% (p = 0.0001) provincially and 0.6% (p = 0.0001) nationally. Uterine cancer deaths were not significantly different from the provincial and national death rates, whereas vulvar and fallopian cancers were too rare to allow for statistical analysis. Gynecologic cancers may be predictive of admission to a palliative care unit.

A kinetic and thermodynamic framework for the Azoarcus group I ribozyme reaction

PubMed Central

Gleitsman, Kristin R.

2014-01-01

Determination of quantitative thermodynamic and kinetic frameworks for ribozymes derived from the Azoarcus group I intron and comparisons to their well-studied analogs from the Tetrahymena group I intron reveal similarities and differences between these RNAs. The guanosine (G) substrate binds to the Azoarcus and Tetrahymena ribozymes with similar equilibrium binding constants and similar very slow association rate constants. These and additional literature observations support a model in which the free ribozyme is not conformationally competent to bind G and in which the probability of assuming the binding-competent state is determined by tertiary interactions of peripheral elements. As proposed previously, the slow binding of guanosine may play a role in the specificity of group I intron self-splicing, and slow binding may be used analogously in other biological processes. The internal equilibrium between ribozyme-bound substrates and products is similar for these ribozymes, but the Azoarcus ribozyme does not display the coupling in the binding of substrates that is observed with the Tetrahymena ribozyme, suggesting that local preorganization of the active site and rearrangements within the active site upon substrate binding are different for these ribozymes. Our results also confirm the much greater tertiary binding energy of the 5′-splice site analog with the Azoarcus ribozyme, binding energy that presumably compensates for the fewer base-pairing interactions to allow the 5′-exon intermediate in self splicing to remain bound subsequent to 5′-exon cleavage and prior to exon ligation. Most generally, these frameworks provide a foundation for design and interpretation of experiments investigating fundamental properties of these and other structured RNAs. PMID:25246656

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…

Antibody Epitope Analysis to Investigate Folded Structure, Allosteric Conformation, and Evolutionary Lineage of Proteins.

PubMed

Wong, Sienna; Jin, J-P

2017-01-01

Study of folded structure of proteins provides insights into their biological functions, conformational dynamics and molecular evolution. Current methods of elucidating folded structure of proteins are laborious, low-throughput, and constrained by various limitations. Arising from these methods is the need for a sensitive, quantitative, rapid and high-throughput method not only analysing the folded structure of proteins, but also to monitor dynamic changes under physiological or experimental conditions. In this focused review, we outline the foundation and limitations of current protein structure-determination methods prior to discussing the advantages of an emerging antibody epitope analysis for applications in structural, conformational and evolutionary studies of proteins. We discuss the application of this method using representative examples in monitoring allosteric conformation of regulatory proteins and the determination of the evolutionary lineage of related proteins and protein isoforms. The versatility of the method described herein is validated by the ability to modulate a variety of assay parameters to meet the needs of the user in order to monitor protein conformation. Furthermore, the assay has been used to clarify the lineage of troponin isoforms beyond what has been depicted by sequence homology alone, demonstrating the nonlinear evolutionary relationship between primary structure and tertiary structure of proteins. The antibody epitope analysis method is a highly adaptable technique of protein conformation elucidation, which can be easily applied without the need for specialized equipment or technical expertise. When applied in a systematic and strategic manner, this method has the potential to reveal novel and biomedically meaningful information for structure-function relationship and evolutionary lineage of proteins. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

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.

Native aggregation as a cause of origin of temporary cellular structures needed for all forms of cellular activity, signaling and transformations.

PubMed

Matveev, Vladimir V

2010-06-09

According to the hypothesis explored in this paper, native aggregation is genetically controlled (programmed) reversible aggregation that occurs when interacting proteins form new temporary structures through highly specific interactions. It is assumed that Anfinsen's dogma may be extended to protein aggregation: composition and amino acid sequence determine not only the secondary and tertiary structure of single protein, but also the structure of protein aggregates (associates). Cell function is considered as a transition between two states (two states model), the resting state and state of activity (this applies to the cell as a whole and to its individual structures). In the resting state, the key proteins are found in the following inactive forms: natively unfolded and globular. When the cell is activated, secondary structures appear in natively unfolded proteins (including unfolded regions in other proteins), and globular proteins begin to melt and their secondary structures become available for interaction with the secondary structures of other proteins. These temporary secondary structures provide a means for highly specific interactions between proteins. As a result, native aggregation creates temporary structures necessary for cell activity."One of the principal objects of theoretical research in any department of knowledge is to find the point of view from which the subject appears in its greatest simplicity."Josiah Willard Gibbs (1839-1903).

Probing the mechanism of insulin fibril formation with insulin mutants.

PubMed

Nielsen, L; Frokjaer, S; Brange, J; Uversky, V N; Fink, A L

2001-07-27

The molecular basis of insulin fibril formation was investigated by studying the structural properties and kinetics of fibril formation of 20 different human insulin mutants at both low pH (conditions favoring monomer/dimer) and at pH 7.4 (conditions favoring tetramer/hexamer). Small-angle X-ray scattering showed insulin to be monomeric in 20% acetic acid, 0.1 M NaCl, pH 2. The secondary structure of the mutants was assessed using far-UV circular dichroism, and the tertiary structure was determined using near-UV circular dichroism, quenching of intrinsic fluorescence by acrylamide and interactions with the hydrophobic probe 1-anilino-8-naphthalene-sulfonic acid (ANS). The kinetics of fibril formation were monitored with the fluorescent dye, Thioflavin T. The results indicate that the monomer is the state from which fibrils arise, thus under some conditions dissociation of hexamers may be rate limiting or partially rate limiting. The insulin mutants were found to retain substantial nativelike secondary and tertiary structure under all conditions studied. The results suggest that fibril formation of the insulin mutants is controlled by specific molecular interactions that are sensitive to variations in the primary structure. The observed effects of several mutations on the rate of fibril formation are inconsistent with a previously suggested model for fibrillation [Brange, J., Whittingham, J., Edwards, D., Youshang, Z., Wollmer, A., Brandenburg, D., Dodson, G., and Finch, J. (1997) Curr. Sci. 72, 470-476]. Two surfaces on the insulin monomer are identified as potential interacting sites in insulin fibrils, one consisting of the residues B10, B16, and B17 and the other consisting of at least the residues A8 and B25. The marked increase in the lag time for fibril formation with mutations to more polar residues, as well as mutations to charged residues, demonstrates the importance of both hydrophobic and electrostatic interactions in the initial stages of fibrillation. A model for insulin fibril formation is proposed in which the formation of a partially folded intermediate is the precursor for associated species on the pathway to fibril formation.

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.

Examining the characteristics of workplace violence in one non-tertiary hospital.

PubMed

Chapman, Rose; Styles, Irene; Perry, Laura; Combs, Shane

2010-02-01

This study sought to determine the prevalence and characteristics of workplace violence directed at a volunteer sample of nurses at one non-tertiary hospital. Respondents' reasons for not reporting these incidents were also investigated. Incidents of workplace violence are increasing worldwide. However, no studies have investigated this phenomenon from the perspective of nurses in Western Australian non-tertiary hospitals. Survey. A survey was distributed to all 332 nurses working in several areas of one non-tertiary hospital in Western Australia to determine their experiences of workplace violence over a 12 month period. Of the 113 nurses who agreed to participate in this study, 75% reported experiencing workplace violence in the previous twelve months. When asked about their most recent incident, 50% of the nurses said they had reported it verbally, mostly to more senior staff. Only 16% of the nurses completed an official incident report. Reasons for not reporting included the view that WPV is just part of the job and the perception that management would not be responsive. This study showed that for this sample of nurses violent events are occurring at a rate that is similar to those reported in other studies. This finding should be of great concern to the organisation and the community in general. Organisations are obliged to improve the safety of the workplace environment for both staff and patients. The findings of our study may be of help to healthcare institutions in developing education programmes for nurses, patients and their friends and relatives to reduce the impact and frequency of workplace violence.

Forensic analysis of tertiary-butyl alcohol (TBA) detections in a hydrocarbon-rich groundwater basin.

PubMed

Quast, Konrad W; Levine, Audrey D; Kester, Janet E; Fordham, Carolyn L

2016-04-01

Tertiary-butyl alcohol (TBA), a high-production volume (HPV) chemical, was sporadically detected in groundwater and coalbed methane (CBM) wells in southeastern Colorado's hydrocarbon-rich Raton Basin. TBA concentrations in shallow water wells averaged 75.1 μg/L, while detections in deeper CBM wells averaged 14.4 μg/L. The detection of TBA prompted a forensic investigation to try to identify potential sources. Historic and recent data were reviewed to determine if there was a discernable pattern of TBA occurrence. Supplemental samples from domestic water wells, monitor wells, CBM wells, surface waters, and hydraulic fracturing (HF) fluids were analyzed for TBA in conjunction with methyl tertiary-butyl ether (MTBE) and ethyl tertiary-butyl ether (ETBE), proxies for evidence of contamination from reformulated gasoline or associated oxygenates. Exploratory microbiological sampling was conducted to determine if methanotrophic organisms co-occurred with TBA in individual wells. Meaningful comparisons of historic TBA data were limited due to widely varying reporting limits. Mapping of TBA occurrence did not reveal any spatial patterns or physical associations with CBM operations or contamination plumes. Additionally, TBA was not detected in HF fluids or surface water samples. Given the widespread use of TBA in industrial and consumer products, including water well completion materials, it is likely that multiple diffuse sources exist. Exploratory data on stable isotopes, dissolved gases, and microbial profiling provide preliminary evidence that methanotrophic activity may be producing TBA from naturally occurring isobutane. Reported TBA concentrations were significantly below a conservative risk-based drinking water screening level of 8000 μg/L derived from animal toxicity data.

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

Manpower Development for Workers in Tertiary Institutions: Distance Learning Approach

ERIC Educational Resources Information Center

Hassan, Moshood Ayinde

2011-01-01

The purpose of this study is to determine the extent to which workers patronize distance learning approach to further their education. Other purposes include: determine problems facing workers in the process of improving their knowledge and skills through distance learning approach; establish the level of attainment of manpower development…

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.

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.

The interdigitating loop of the enolase superfamily as a specificity binding determinant or 'flying buttress'.

PubMed

Bearne, Stephen L

2017-05-01

Enzymes of the enolase superfamily (ENS) are mechanistically diverse, yet share a common partial reaction (abstraction of the α-proton from a carboxylate substrate). While the catalytic machinery responsible for the deprotonation reaction has been conserved, divergent evolution has led to numerous ENS members that catalyze different overall reactions. This rich functional diversity has made the ENS an excellent model system for developing the approaches necessary to validate enzyme function. However, enzymes of the ENS also share a common bidomain structure ((β/α) 7 β-barrel domain and α+β capping domain) which makes validation of function from structural information challenging. This review presents a comparative survey of the structural data obtained over the past decade for enzymes from all seven subgroups that comprise the ENS. Of the seven ENS subgroups (enolase, mandelate racemase (MR), muconate lactonizing enzyme, β-methylaspartate ammonia lyase, d-glucarate dehydratase, d-mannonate dehydratase (ManD), and galactarate dehydratase 2), only enzymes of the MR and ManD subgroups exhibit an additional feature of structural complexity-an interdigitating loop. This loop emanates from one protomer of a homodimeric pair and penetrates into the adjacent, symmetry-related protomer to either contribute a binding determinant to the active site of the adjacent protomer, or act as a 'flying buttress' to support residues of the active site. The analysis presented in this review suggests that the interdigitating loop is the only gross structural element that permits functional distinction between ENS subgroups at the tertiary level of protein structure. Copyright © 2017 Elsevier B.V. All rights reserved.

Solution structure of dimeric Mnt repressor (1-76).

PubMed

Burgering, M J; Boelens, R; Gilbert, D E; Breg, J N; Knight, K L; Sauer, R T; Kaptein, R

1994-12-20

Wild-type Mnt repressor of Salmonella bacteriophage P22 is a tetrameric protein of 82 residues per monomer. A C-terminal deletion mutant of the repressor denoted Mnt (1-76) is a dimer in solution. The structure of this dimer has been determined using NMR. The NMR assignments of the majority of the 1H, 15N, and 13C resonances were obtained using 2D and triple-resonance 3D techniques. Elements of secondary structure were identified on the basis of characteristic sequential and medium range NOEs. For the structure determination more than 1000 NOEs per monomer were obtained, and structures were generated using distance geometry and restrained simulated annealing calculations. The discrimination of intra- vs intermonomer NOEs was based upon the observation of intersubunit NOEs in [15N,13C] double half-filtered NOESY experiments. The N-terminal part of Mnt (residues 1-44), which shows a 40% sequence homology with the Arc repressor, has a similar secondary and tertiary structure. Mnt (1-76) continues with a loop region of irregular structure, a third alpha-helix, and a random coil C-terminal peptide. Analysis of the secondary structure NOEs, the exchange rates, and the backbone chemical shifts suggests that the carboxy-terminal third helix is less stable than the remainder of the protein, but the observation of intersubunit NOEs for this part of the protein enables the positioning of this helix. The rsmd's between the backbone atoms of the N-terminal part of the Mnt repressor (residues 5-43, 5'-43') and the Arc repressor is 1.58 A, and between this region and the corresponding part of the MetJ repressor 1.43 A.

Brønsted acidity of protic ionic liquids: a modern ab initio valence bond theory perspective.

PubMed

Patil, Amol Baliram; Mahadeo Bhanage, Bhalchandra

2016-09-21

Room temperature ionic liquids (ILs), especially protic ionic liquids (PILs), are used in many areas of the chemical sciences. Ionicity, the extent of proton transfer, is a key parameter which determines many physicochemical properties and in turn the suitability of PILs for various applications. The spectrum of computational chemistry techniques applied to investigate ionic liquids includes classical molecular dynamics, Monte Carlo simulations, ab initio molecular dynamics, Density Functional Theory (DFT), CCSD(t) etc. At the other end of the spectrum is another computational approach: modern ab initio Valence Bond Theory (VBT). VBT differs from molecular orbital theory based methods in the expression of the molecular wave function. The molecular wave function in the valence bond ansatz is expressed as a linear combination of valence bond structures. These structures include covalent and ionic structures explicitly. Modern ab initio valence bond theory calculations of representative primary and tertiary ammonium protic ionic liquids indicate that modern ab initio valence bond theory can be employed to assess the acidity and ionicity of protic ionic liquids a priori.

High-resolution reversible folding of hyperstable RNA tetraloops using molecular dynamics simulations

PubMed Central

Chen, Alan A.; García, Angel E.

2013-01-01

We report the de novo folding of three hyperstable RNA tetraloops to 1–3 Å rmsd from their experimentally determined structures using molecular dynamics simulations initialized in the unfolded state. RNA tetraloops with loop sequences UUCG, GCAA, or CUUG are hyperstable because of the formation of noncanonical loop-stabilizing interactions, and they are all faithfully reproduced to angstrom-level accuracy in replica exchange molecular dynamics simulations, including explicit solvent and ion molecules. This accuracy is accomplished using unique RNA parameters, in which biases that favor rigid, highly stacked conformations are corrected to accurately capture the inherent flexibility of ssRNA loops, accurate base stacking energetics, and purine syn-anti interconversions. In a departure from traditional quantum chemistrycentric approaches to force field optimization, our parameters are calibrated directly from thermodynamic and kinetic measurements of intra- and internucleotide structural transitions. The ability to recapitulate the signature noncanonical interactions of the three most abundant hyperstable stem loop motifs represents a significant milestone to the accurate prediction of RNA tertiary structure using unbiased all-atom molecular dynamics simulations. PMID:24043821

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

Crystal structure of bacillus subtilis YdaF protein : a putative ribosomal N-acetyltransferase.

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

Brunzelle, J. S.; Wu, R.; Korolev, S. V.

2004-12-01

Comparative sequence analysis suggests that the ydaF gene encodes a protein (YdaF) that functions as an N-acetyltransferase, more specifically, a ribosomal N-acetyltransferase. Sequence analysis using basic local alignment search tool (BLAST) suggests that YdaF belongs to a large family of proteins (199 proteins found in 88 unique species of bacteria, archaea, and eukaryotes). YdaF also belongs to the COG1670, which includes the Escherichia coli RimL protein that is known to acetylate ribosomal protein L12. N-acetylation (NAT) has been found in all kingdoms. NAT enzymes catalyze the transfer of an acetyl group from acetyl-CoA (AcCoA) to a primary amino group. Formore » example, NATs can acetylate the N-terminal {alpha}-amino group, the {epsilon}-amino group of lysine residues, aminoglycoside antibiotics, spermine/speridine, or arylalkylamines such as serotonin. The crystal structure of the alleged ribosomal NAT protein, YdaF, from Bacillus subtilis presented here was determined as a part of the Midwest Center for Structural Genomics. The structure maintains the conserved tertiary structure of other known NATs and a high sequence similarity in the presumed AcCoA binding pocket in spite of a very low overall level of sequence identity to other NATs of known structure.« less

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.

Freestanding midwifery units: Maternal and neonatal outcomes following transfer.

PubMed

Monk, Amy R; Grigg, Celia P; Foureur, Maralyn; Tracy, Mark; Tracy, Sally K

2017-03-01

the viability of freestanding midwifery units in Australia is restricted, due to concerns over their safety, particularly for women and babies who, require transfer. to compare the maternal and neonatal birth outcomes of women who planned, to give birth at freestanding midwifery units and subsequently, transferred to a tertiary maternity unit to the maternal and neonatal, outcomes of a low-risk cohort of women who planned to give birth in, tertiary maternity unit. a descriptive study compared two groups of women with low-risk singleton, pregnancies who were less than 28 weeks pregnant at booking: women who, planned to give birth at a freestanding midwifery unit (n=494) who, transferred to a tertiary maternity unit during the antenatal, intrapartum or postnatal periods (n=260) and women who planned to give, birth at a tertiary maternity unit (n=3157). Primary outcomes were mode, of birth, Apgar score of less than 7 at 5minutes and admission to, special care nursery or neonatal intensive care. the proportion of women who experienced a caesarean section was lower, among the freestanding midwifery unit women who transferred during the, intrapartum/postnatal period compared to women in the tertiary maternity, unit group (16.1% versus 24.8% respectively). Other outcomes were, comparable between the cohorts. Rates of primary outcomes in relation to, stage of transfer varied when stratified by parity. these descriptive results support the provision of care in freestanding, midwifery units as an alternative to tertiary maternity units for women, with low risk pregnancies at the time of booking. A larger study, powered, to determine statistical significance of any differences in outcomes, is, required. Copyright © 2017 Elsevier Ltd. All rights reserved.

Frequency of human immunodeficiency virus infection among students of tertiary and secondary institutions in an endemic state.

PubMed

Abubakar, Abdulazeez

2012-04-01

Students are pivotal to manpower development and technological advancement of any nation. Nigerian nation was recently ranked third human immunodeficiency virus (HIV) most endemic nation in the world The study was designed to determine the frequency of HIV infection among Nigerian tertiary and secondary institution students. A HIV screening test was conducted on 1,978 apparently healthy students composed of 981 males and 997 females aged 11-35 years, randomly selected from some Nigerian tertiary and secondary institutions Overall, the sero-prevalence rate of 13.7% was recorded consisting 9.9% in the tertiary and 3.8% in secondary institutions. The distribution of the infection showed no significant difference by age (χ(2)=1.07, P>0.05) and by gender (χ(2)=0.85, P>0.05). Also, the prevalence had no significant association with the settlement of students (χ(2)=0.96, P>0.05) and the status of educational institutions (χ(2)=1.42, P>0.05). The findings indicate a high HIV prevalence rate among students in this part of the globe. General behavioral changes about sex among the students are suggested.

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.

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.

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

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

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

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

Loop-to-helix transition in the structure of multidrug regulator AcrR at the entrance of the drug-binding cavity.

PubMed

Manjasetty, Babu A; Halavaty, Andrei S; Luan, Chi-Hao; Osipiuk, Jerzy; Mulligan, Rory; Kwon, Keehwan; Anderson, Wayne F; Joachimiak, Andrzej

2016-04-01

Multidrug transcription regulator AcrR from Salmonella enterica subsp. enterica serovar Typhimurium str. LT2 belongs to the tetracycline repressor family, one of the largest groups of bacterial transcription factors. The crystal structure of dimeric AcrR was determined and refined to 1.56Å resolution. The tertiary and quaternary structures of AcrR are similar to those of its homologs. The multidrug binding site was identified based on structural alignment with homologous proteins and has a di(hydroxyethyl)ether molecule bound. Residues from helices α4 and α7 shape the entry into this binding site. The structure of AcrR reveals that the extended helical conformation of helix α4 is stabilized by the hydrogen bond between Glu67 (helix α4) and Gln130 (helix α7). Based on the structural comparison with the closest homolog structure, the Escherichia coli AcrR, we propose that this hydrogen bond is responsible for control of the loop-to-helix transition within helix α4. This local conformational switch of helix α4 may be a key step in accessing the multidrug binding site and securing ligands at the binding site. Solution small-molecule binding studies suggest that AcrR binds ligands with their core chemical structure resembling the tetracyclic ring of cholesterol. Copyright © 2016. Published by Elsevier Inc.

Navigating 3D electron microscopy maps with EM-SURFER.

PubMed

Esquivel-Rodríguez, Juan; Xiong, Yi; Han, Xusi; Guang, Shuomeng; Christoffer, Charles; Kihara, Daisuke

2015-05-30

The Electron Microscopy DataBank (EMDB) is growing rapidly, accumulating biological structural data obtained mainly by electron microscopy and tomography, which are emerging techniques for determining large biomolecular complex and subcellular structures. Together with the Protein Data Bank (PDB), EMDB is becoming a fundamental resource of the tertiary structures of biological macromolecules. To take full advantage of this indispensable resource, the ability to search the database by structural similarity is essential. However, unlike high-resolution structures stored in PDB, methods for comparing low-resolution electron microscopy (EM) density maps in EMDB are not well established. We developed a computational method for efficiently searching low-resolution EM maps. The method uses a compact fingerprint representation of EM maps based on the 3D Zernike descriptor, which is derived from a mathematical series expansion for EM maps that are considered as 3D functions. The method is implemented in a web server named EM-SURFER, which allows users to search against the entire EMDB in real-time. EM-SURFER compares the global shapes of EM maps. Examples of search results from different types of query structures are discussed. We developed EM-SURFER, which retrieves structurally relevant matches for query EM maps from EMDB within seconds. The unique capability of EM-SURFER to detect 3D shape similarity of low-resolution EM maps should prove invaluable in structural biology.

American Tertiary mollusks of the genus Clementia

USGS Publications Warehouse

Woodring, W.P.

1927-01-01

Aside from its value as an aid in determining the age of Tertiary beds, the chief interest of the genus Clementia lies in the anomalous features of its present and former distribution. An attempt is made in this paper to trace its geologic history, to point out its paleobiologic significance, and to describe all the known American Tertiary species. The fossils from Colombia used in preparing this report were collected during explorations made under the direction of Dr. 0. B. Hopkins, chief geologist of the Imperial Oil Co. (Ltd.), who kindly donated them to the United States National Museum. Dr. T. Wayland Vaughan, of the Scripps Institution of Oceanography, furnished information relating to specimens collected by him in Mexico. Dr. Bruce L. Clark, of the University of California; Dr. G. Dallas Hanna, of the California Academy of Sciences; Dr. H. A. Pilsbry, of the Philadelphia Academy of Natural Sciences; and Dr. W. D. Matthew, of the American Museum of Natural History, generously loaned type specimens and other material. Doctor Clark and Doctor Hanna also gave information concerning the Tertiary species from California. Mr. Ralph B. Stewart, of the University of California, read the manuscript, and I have taken advantage of his suggestions. I am also indebted to Mr. L. R. Cox, of the British Museum, for information relating to the fossil species from Persia, Zanzibar, and Burma, and to Dr. Axel A. Olsson, of the International Petroleum Co., for data concerning undescribed Tertiary species from Peru.

Do family and neighbourhood matter in secondary school completion? A multilevel study of determinants and their interactions in a life-course perspective

PubMed Central

Myhr, Arnhild; Lillefjell, Monica; Espnes, Geir Arild; Halvorsen, Thomas

2017-01-01

Background Completion of secondary education is important for individuals’ future health and health behaviour. The fundamental purpose of this study is to investigate the variation and clustering of school completion in families and neighbourhoods. Secondly, we aim to examine the impact of individuals’ family structure and neighbourhood of residence and examine to what extent parental education level moderates these associations. Methods Longitudinal register data for 30% of the entire Norwegian population aged 21–27 years in 2010 (N = 107,003) was extracted from Statistic Norway´s event database. Three-level logistic regression models, which incorporated individual, family, and neighbourhood contextual factors, were applied to estimate the family and neighbourhood general contextual effects and detect possible educational differences in the impact of family structure and urban place of residence in school completion. Results Completion rates were significantly higher within families with higher education level (79% in tertiary educated families vs. 61% and 48% in secondary and primary educated families respectively) and were strongly correlated within families (ICC = 39.6) and neighbourhoods (ICC = 5.7). Several structural factors at the family level negatively associated with school completion (e.g., family disruption, large family size, and young maternal age) were more prevalent and displayed more negative impact among primary educated individuals. Urban residence was associated with school completion, but only among the tertiary educated. Conclusions Investment in the resources in the individuals’ immediate surroundings, including family and neighbourhood, may address a substantial portion of the social inequalities in the completion of upper secondary education. The high intra-familial correlation in school completion suggests that public health policies and future research should acknowledge family environments in order to improve secondary education completion rates among young people within lower educated families. PMID:28222115

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

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.

Molecular evolution of FtsZ protein sequences encoded within the genomes of archaea, bacteria, and eukaryota.

PubMed

Vaughan, Sue; Wickstead, Bill; Gull, Keith; Addinall, Stephen G

2004-01-01

The FtsZ protein is a polymer-forming GTPase which drives bacterial cell division and is structurally and functionally related to eukaryotic tubulins. We have searched for FtsZ-related sequences in all freely accessible databases, then used strict criteria based on the tertiary structure of FtsZ and its well-characterized in vitro and in vivo properties to determine which sequences represent genuine homologues of FtsZ. We have identified 225 full-length FtsZ homologues, which we have used to document, phylum by phylum, the primary sequence characteristics of FtsZ homologues from the Bacteria, Archaea, and Eukaryota. We provide evidence for at least five independent ftsZ gene-duplication events in the bacterial kingdom and suggest the existence of three ancestoral euryarchaeal FtsZ paralogues. In addition, we identify "FtsZ-like" sequences from Bacteria and Archaea that, while showing significant sequence similarity to FtsZs, are unlikely to bind and hydrolyze GTP.

Determination of Trophic Structure in Selected Freshwater Ecosystems by using Stable Isotope Analysis

PubMed Central

Zainordin, ‘Amila Faqhira; Ab Hamid, Suhaila

2017-01-01

Stable isotope analysis has been used extensively to establish trophic relationships in many ecosystems. Present study utilised stable isotope signatures of carbon and nitrogen to identify trophic structure of aquatic food web in river and rice field ecosystems in Perak, northern peninsular Malaysia. The mean δ13C values of all producers ranged from −35.29 ± 0.21 to −26.00 ± 0.050‰. The greatest δ15N values noted was in zenarchopterid fish with 9.68 ± 0.020‰. The δ15N values of aquatic insects ranged between 2.59 ± 0.107 in Elmidae (Coleoptera) and 8.11 ± 0.022‰ in Nepidae (Hemiptera). Correspondingly, with all the δ13C and δ15N values recorded, it can be deduced that there are four trophic levels existed in the freshwater ecosystems which started with the producer (plants), followed by primary consumer (aquatic insects and non-predatory fish), secondary consumer (invertebrate predators) and lastly tertiary consumer (vertebrate predators). PMID:28890758

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

PubMed

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

1988-04-07

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

Bio-, Magneto- and event-stratigraphy across the K-T boundary

NASA Technical Reports Server (NTRS)

Preisinger, A.; Stradner, H.; Mauritsch, H. J.

1988-01-01

Determining the time and the time structure of rare events in geology can be accomplished by applying three different and independent stratigraphic methods: Biostratigraphy, magneto-stratigraphy and event-stratigraphy. The optimal time resolution of the two former methods is about 1000 years, while by means of event-stratigraphy a resolution of approximately one year can be achieved. For biostratigraphy across the Cretaceous-Tertiary (K-T) boundary micro- and nannofossils have been found best suited. The qualitative and quantitative analyses of minerals and trace elements across the K-T boundary show anomalies on a millimeter scale and permit conclusions regarding the time structure of the K-T event itself. The results of the analyses find a most consistent explanation by the assumption of an extraterrestrial impact. The main portion of the material rain from the atmosphere evidently was deposited within a short time. The long-time components consist of the finest portion of the material rain from the atmosphere and the transported and redeposited fall-out.

PREvaIL, an integrative approach for inferring catalytic residues using sequence, structural, and network features in a machine-learning framework.

PubMed

Song, Jiangning; Li, Fuyi; Takemoto, Kazuhiro; Haffari, Gholamreza; Akutsu, Tatsuya; Chou, Kuo-Chen; Webb, Geoffrey I

2018-04-14

Determining the catalytic residues in an enzyme is critical to our understanding the relationship between protein sequence, structure, function, and enhancing our ability to design novel enzymes and their inhibitors. Although many enzymes have been sequenced, and their primary and tertiary structures determined, experimental methods for enzyme functional characterization lag behind. Because experimental methods used for identifying catalytic residues are resource- and labor-intensive, computational approaches have considerable value and are highly desirable for their ability to complement experimental studies in identifying catalytic residues and helping to bridge the sequence-structure-function gap. In this study, we describe a new computational method called PREvaIL for predicting enzyme catalytic residues. This method was developed by leveraging a comprehensive set of informative features extracted from multiple levels, including sequence, structure, and residue-contact network, in a random forest machine-learning framework. Extensive benchmarking experiments on eight different datasets based on 10-fold cross-validation and independent tests, as well as side-by-side performance comparisons with seven modern sequence- and structure-based methods, showed that PREvaIL achieved competitive predictive performance, with an area under the receiver operating characteristic curve and area under the precision-recall curve ranging from 0.896 to 0.973 and from 0.294 to 0.523, respectively. We demonstrated that this method was able to capture useful signals arising from different levels, leveraging such differential but useful types of features and allowing us to significantly improve the performance of catalytic residue prediction. We believe that this new method can be utilized as a valuable tool for both understanding the complex sequence-structure-function relationships of proteins and facilitating the characterization of novel enzymes lacking functional annotations. Copyright © 2018 Elsevier Ltd. 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

Effects of solution conditions on methionine oxidation in albinterferon alfa-2b and the role of oxidation in its conformation and aggregation.

PubMed

Chou, Danny K; Krishnamurthy, Rajesh; Manning, Mark Cornell; Randolph, Theodore W; Carpenter, John F

2013-02-01

Physical and chemical degradation of therapeutic proteins can occur simultaneously. In this study, our first objective was to investigate how solution conditions that impact conformational stability of albinterferon alfa-2b, a recombinant fusion protein, modulate rates of methionine (Met) oxidation. Another objective of this work was to determine whether oxidation affects conformation and rate of aggregation of the protein. The protein was subjected to oxidation in solutions of varying pH, ionic strength, and excipients by the addition of 0.02% tertiary-butyl hydroperoxide (TBHP). The rate of formation of Met-sulfoxide species was monitored by reversed-phase high-performance liquid chromatography and compared across solution conditions. Albinterferon alfa-2b exhibited susceptibility to Met oxidation during exposure to TBHP that was highly dependent on solution parameters, but there was not a clear correlation between oxidation rate and protein conformational stability. Met oxidation resulted in significant perturbation of both secondary and tertiary structure of albinterferon alfa-2b as shown by both far-ultraviolet (UV) and near-UV circular dichroism. Moreover, oxidation of the protein caused a noticeable reduction in the protein's resistance to thermal denaturation. Surprisingly, despite its negative effect on solution structure and conformational stability, oxidation actually reduced the protein's aggregation rate during agitation at room temperature as well as during quiescent incubation at 40°C. Oxidation of the protein resulted in improved colloidal stability of the protein, which is manifested by a more positive B(22) value in the oxidized protein. Thus, the reduced aggregation rate after oxidation suggests that increased colloidal stability of oxidized albinterferon alfa-2b counteracted oxidation-induced decreases in conformational stability. Copyright © 2012 Wiley Periodicals, Inc.

An Examination of the Local Cellular Immune Response to Examples of Both Ductal Carcinoma In Situ (DCIS) of the Breast and DCIS With Microinvasion, With Emphasis on Tertiary Lymphoid Structures and Tumor Infiltrating Lymphoctytes.

PubMed

Kim, Ahrong; Heo, Sun-Hee; Kim, Young-Ae; Gong, Gyungyub; Jin Lee, Hee

2016-07-01

We tried to describe cellular immune response (tertiary lymphoid structures (TLSs), lymphoid aggregates, tumor infiltrating lymphocytes (TILs)) in neoplastic microenvironment of ductal carcinoma in situ (DCIS) with or without associated microinvasion. The histopathologic parameters of 177 DCIS and 27 DCIS with microinvasion were evaluated. We determined number of ducts involved by DCIS, and calculated percentage of these ducts surrounded by TLSs. TILs were quantitated in 27 microinvasive cases. Tumors having higher percentage of DCIS ducts associated with TLSs had higher incidence of microinvasion (P < .001). Percentage of DCIS ducts involved by TLSs was also higher in hormone receptor (HR)-/human epidermal growth factor receptor 2 (HER2)+ and TNBC subtypes of DCIS than in HR+/HER2- and HR+/HER2+ subtypes (38.04 ± 25.8%, 32.6 ± 32.4%, 2.5 ± 7.3% and 17.4 ± 23.3%, respectively, P < .001). In DCIS without microinvasion, HR+/HER2- subtype predominated (P < .001). In microinvasive cases, HR-/HER2+ subtype was most common. TNBC was more common in microinvasive carcinoma than DCIS (P < .001). Among 27 microinvasive ductal carcinomas, increased TLS amount was associated with increased TILs (P = .013). TLS abundance around DCIS was associated with HER2+ and TNBC subtypes and microinvasion. Pathologists should be aware of microinvasion when diagnosing DCIS lesions with abundant TLSs. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Stable coordination of the inhibitory Ca2+ ion at MIDAS in integrin CD11b/CD18 by an antibody-derived ligand aspartate: Implications for integrin regulation and structure-based drug design

PubMed Central

Mahalingam, Bhuvaneshwari; Ajroud, Kaouther; Alonso, Jose Luis; Anand, Saurabh; Adair, Brian; Horenstein, Alberto L; Malavasi, Fabio; Xiong, Jian-Ping; Arnaout, M. Amin

2011-01-01

A central feature of integrin interaction with physiologic ligands is the monodentate binding of a ligand carboxylate to a Mg2+ ion hexacoordinated at the metal-ion-dependent-adhesion site (MIDAS) in the integrin A-domain. This interaction stabilizes the A-domain in the high-affinity state, which is distinguished from the default low-affinity state by tertiary changes in the domain that culminate in cell adhesion. Small molecule ligand-mimetic integrin antagonists act as partial agonists, eliciting similar activating conformational changes in the A-domain, which has contributed to paradoxical adhesion and increased patient mortality in large clinical trials. As with other ligand-mimetic integrin antagonists, the function-blocking monoclonal antibody (mAb) 107 binds MIDAS of integrin CD11b/CD18 A-domain (CD11bA), but in contrast, it favors the inhibitory Ca2+ ion over Mg2+ at MIDAS. We determined the crystal structures of the Fab fragment of mAb 107 complexed to the low- and high-affinity states of CD11bA. Favored binding of Ca2+ at MIDAS is caused by the unusual symmetric bidentate ligation of a Fab-derived ligand Asp to a heptacoordinated MIDAS Ca2+. Binding of Fab 107 to CD11bA did not trigger the activating tertiary changes in the domain or in the full-length integrin. These data show that denticity of the ligand Asp/Glu can modify divalent cation selectivity at MIDAS and hence integrin function. Stabilizing the Ca2+ ion at MIDAS by bidentate ligation to a ligand Asp/Glu may provide one approach for designing pure integrin antagonists. PMID:22095715

Preliminary location and age database for invertebrate fossils collected in the San Francisco Bay region, California

USGS Publications Warehouse

Parker, John M.; West, William B.; Malmborg, William T.; Brabb, Earl E.

2003-01-01

Most geologic maps published for central California in the past century have been made without the benefit of microfossils. The age of Cretaceous and Tertiary rocks in the structurally complex sedimentary formations of the Coast Ranges is critical in determining stratigraphic succession and in determining whether the juxtapositon of similar appearing formations means that a fault is present. Since the 1930’s, at least, oil company geologists have used microfossils to assist them in geologic mapping and in determining the environments of deposition of sedimentary rocks. This information has been confidential, but in the past 20 years the attitude of petroleum companies about this information has changed, and much material is now available. We report here on approximately 4,700 samples, largely foraminifers, from surface localities in the San Francisco Bay region of California. The information contained here can be used to update geologic maps, to analyze the depth and temperature of ocean water covering parts of California during the Mesozoic and Cenozoic eras, and for solving other geologic problems.

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…

Equilibration of tert-alkylphenols (thermodynamic analysis of the alkylation of phenols using branched-chain olefins)

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

Nesterova, T.N.; Malova, T.N.; Pil'shchikov, V.A.

1985-09-01

The authors describe the results of a study to evaluate the thermodynamic properties of t-Alk phi. These results, combined with earlier results, have enabled the authors to complete a thermodynamic analysis of the process for preparing tertiary alkylphenols which are widely used as additives in lubricating and fuel oils. Research was conducted over a fairly wide temperature range, in which the median temperature value corresponds to the upper temperature limit for a continuous process utilizing a type KU-2 ion-exchange resin catalyst; continuous operations are currently the most widely used method for industrial preparation of alkylphenols. Experimentally determined values of themore » equilibrium constants in a table indicate that they are influenced primarily by the nature of the reaction, and do not depend on the size of the tertiary alkyl substituents. Data in another table demonstrate that the thermodynamic properties of a given reaction are determined by the reaction type and are independent of the size of the tertiary alkylphenols. It was discovered that in order to increase the yield of the desired tert-alkylphenol product, the process should be carried out at the minimum possible temperature, using catalysts which are sufficiently active to guarantee thermodynamic control.« less

Cenozoic Ignimbrites, Source Calderas, Relict Magma Chambers, and Tectonic Settings: Perspectives from Cordilleran North America (Invited)

NASA Astrophysics Data System (ADS)

Lipman, P. W.

2009-12-01

In the early 1960s, new concepts and innovative techniques coalesced spectacularly to improve understanding of Tertiary pyroclastic volcanism in North America. Spotty recognition of welded tuff, among rocks mostly described as silicic lava flows, exploded with identification of individual ignimbrite sheets, some having volumes >103 km3 and extending >100 km from source calderas. R.l. Smith, during study of the Bandelier Tuff in New Mexico, documented complexities of welding and crystallization zones that provided a genetic framework (cooling units) for ignimbrite studies (even while confusion continues in some areas where talus and vegetation obscure bench-forming contact zones between densely welded cliffs). Also in the 1960s, application of isotopic age determinations (initially K-Ar, now largely superceded by 40Ar/39Ar laser fusion) and precise paleomagnetic pole directions became key tools for correlating ignimbrites, deciphering eruptive histories, and determining volcano-tectonic patterns. Dated ignimbrites provide unique stratigraphic markers within volcanic field, as well as datums for regional structures and the shifting patterns of volcanism related to global plate motions--another happy coincidence in the 1960s as plate-tectonic models were formulated. Tertiary ignimbrite flare-ups along the Cordilleran margin increasingly are recognized as coinciding with inception of regional extension, especially during transitions from episodes of low-angle convergence. Many large caldera sources for the Tertiary ignimbrites have now been identified, in place of prior vague concepts of “volcano-tectonic depressions”, especially as the contrasts between thin outflow and thickly ponded intracaldera ignimbrite with interleaved collapse breccia became appreciated. Multi-km-thick fills in many calderas document that collapse begins early during large ignimbrite eruptions, and downsag inception was succeeded by breakage along ring faults. Resurgent uplift has been identified at many ignimbrite calderas, building on the pioneering observations of van Bemmelen at Lake Toba, Indonesia. Still many Tertiary caldera systems remain poorly understood where buried beneath younger rocks, others completely eroded to levels of subvolcanic granitic plutons. Links between silicic volcanism and batholith formation in continental crust continue a major research focus; improved petrologic, isotopic, and geophysical techniques are helping evaluate compositional and age relations between extrusive and intrusive components, as well as present-day intrusion geometry relative to times of peak volcanism. Ignimbrites that preserve quenched compositional gradients, commonly from rhyolite upward into crystal-rich dacite, were early recognized as special opportunities for magma-chamber studies, especially as analytical methods improved (XRF and INAA rock chemistry, microprobe mineral compositions, radiogenic and stable isotope geochemistry). These demonstrated the importance of mafic magma from the mantle, melting/assimilation in the lower crust, and mixing of diverse magmas during rise and eruption, even as recent studies by electron and/or ion probe documented complex crystal cargos (mixed phenocrysts, xenocrysts, and antecrysts).

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.

Use of Zymography in Trypanosomiasis Studies.

PubMed

Monte, Jéssyka Fernanda Santiago; Moreno, Cláudia Jassica Gonçalves; Monteiro, Joana Patrícia Molato Figueiredo Lopes; de Oliveira Rocha, Hugo Alexandre; Ribeiro, Aline Rimoldi; Silva, Marcelo Sousa

2017-01-01

Zymography assay is a semiquantitative technique, very sensitive, and commonly used to determine metalloproteinase levels in different types of biological samples, including tissues, cells, and extracts of protein. Samples containing metalloproteinases are loaded onto a polyacrylamide gel containing sodium dodecyl sulphate (SDS) and a specific substrate (gelatin, casein, collagen, etc.). Then proteins are allowed to migrate under an electric current and the distance of migration is inversely correlated with the molecular weight. After migration, the gel is placed in a renaturing buffer to allow proteins to regain their tertiary structure, necessary for enzymatic activity (metalloproteinase activity). In the context of infections caused by trypanosomatids (Leishmania spp., Trypanosoma cruzi, and Trypanosoma brucei), the characterization of metalloproteinase by zymography can contribute to the comprehension of the pathogenesis mechanisms and host-parasite interaction.

Identification of tertiary butyl alcohol (TBA)-utilizing organisms in BioGAC reactors using 13C-DNA stable isotope probing.

PubMed

Aslett, Denise; Haas, Joseph; Hyman, Michael

2011-09-01

Biodegradation of the gasoline oxygenates methyl tertiary-butyl ether (MTBE) and ethyl tertiary-butyl ether (ETBE) can cause tertiary butyl alcohol (TBA) to accumulate in gasoline-impacted environments. One remediation option for TBA-contaminated groundwater involves oxygenated granulated activated carbon (GAC) reactors that have been self-inoculated by indigenous TBA-degrading microorganisms in ground water extracted from contaminated aquifers. Identification of these organisms is important for understanding the range of TBA-metabolizing organisms in nature and for determining whether self-inoculation of similar reactors is likely to occur at other sites. In this study (13)C-DNA-stable isotope probing (SIP) was used to identify TBA-utilizing organisms in samples of self-inoculated BioGAC reactors operated at sites in New York and California. Based on 16S rRNA nucleotide sequences, all TBA-utilizing organisms identified were members of the Burkholderiales order of the β-proteobacteria. Organisms similar to Cupriavidus and Methylibium were observed in both reactor samples while organisms similar to Polaromonas and Rhodoferax were unique to the reactor sample from New York. Organisms similar to Hydrogenophaga and Paucibacter strains were only detected in the reactor sample from California. We also analyzed our samples for the presence of several genes previously implicated in TBA oxidation by pure cultures of bacteria. Genes Mpe_B0532, B0541, B0555, and B0561 were all detected in (13)C-metagenomic DNA from both reactors and deduced amino acid sequences suggested these genes all encode highly conserved enzymes. One gene (Mpe_B0555) encodes a putative phthalate dioxygenase-like enzyme that may be particularly appropriate for determining the potential for TBA oxidation in contaminated environmental samples.

Mineralogical characteristics of Cretaceous-Tertiary kaolins of the Douala Sub-Basin, Cameroon

NASA Astrophysics Data System (ADS)

Bukalo, Nenita N.; Ekosse, Georges-Ivo E.; Odiyo, John O.; Ogola, Jason S.

2018-05-01

As a step in evaluating the quality of Cretaceous-Tertiary kaolins of the Douala Sub-Basin, their mineralogical characteristics were determined. The X-ray diffractometry technique was used to identify and quantify the mineral phases present in bulk and <2 μm fractions. Scanning electron microscopy was used to determine the micromorphology of <2 μm fractions kaolins. Thermal analyses (derivative thermal gravimetric analysis, thermal gravimetric analysis, and heat flow) were conducted to further characterise the kaolins. The main mineral phases present in the studied Cretaceous-Tertiary kaolins of the Douala Sub-Basin were kaolinite > smectite > illite, with mean values of 33.01 > 11.20 > 4.41 wt %; and 72.23 > 10.69 > 4.69 wt %, in bulk and <2 μm fractions, respectively. The kaolins, micromorphologically, consisted of pseudo-hexagonal and thin platy particles; swirl-textured particles; and books or stacks of kaolinite particles. Three main reactions occurred during heating of the kaolins: a low temperature endothermic reaction, observed between 48 and 109 °C; a second low temperature peak, observed between 223 and 285 °C; and a third endothermic peak was found between 469 and 531 °C. In addition, an exothermic reaction also occurred between 943 and 988 °C in some of the samples. The absence of primary minerals such as feldspars and micas in most of these kaolins is an indication of intensive weathering, probably due to the humid tropical climate of the region. The different morphologies suggested that these kaolins might have been transported. Therefore, a humid tropical climate was responsible for the formation of Cretaceous-Tertiary kaolins of the Douala Sub-Basin through intense weathering of surrounding volcanic and metamorphic rocks.

Molecular dynamics of individual alpha-helices of bacteriorhodopsin in dimyristol phosphatidylocholine. I. Structure and dynamics.

PubMed

Woolf, T B

1997-11-01

Understanding the role of the lipid bilayer in membrane protein structure and dynamics is needed for tertiary structure determination methods. However, the molecular details are not well understood. Molecular dynamics computer calculations can provide insight into these molecular details of protein:lipid interactions. This paper reports on 10 simulations of individual alpha-helices in explicit lipid bilayers. The 10 helices were selected from the bacteriorhodopsin structure as representative alpha-helical membrane folding components. The bilayer is constructed of dimyristoyl phosphatidylcholine molecules. The only major difference between simulations is the primary sequence of the alpha-helix. The results show dramatic differences in motional behavior between alpha-helices. For example, helix A has much smaller root-mean-squared deviations than does helix D. This can be understood in terms of the presence of aromatic residues at the interface for helix A that are not present in helix D. Additional motions are possible for the helices that contain proline side chains relative to other amino acids. The results thus provide insight into the types of motion and the average structures possible for helices within the bilayer setting and demonstrate the strength of molecular simulations in providing molecular details that are not directly visualized in experiments.

Refinement of protein termini in template-based modeling using conformational space annealing.

PubMed

Park, Hahnbeom; Ko, Junsu; Joo, Keehyoung; Lee, Julian; Seok, Chaok; Lee, Jooyoung

2011-09-01

The rapid increase in the number of experimentally determined protein structures in recent years enables us to obtain more reliable protein tertiary structure models than ever by template-based modeling. However, refinement of template-based models beyond the limit available from the best templates is still needed for understanding protein function in atomic detail. In this work, we develop a new method for protein terminus modeling that can be applied to refinement of models with unreliable terminus structures. The energy function for terminus modeling consists of both physics-based and knowledge-based potential terms with carefully optimized relative weights. Effective sampling of both the framework and terminus is performed using the conformational space annealing technique. This method has been tested on a set of termini derived from a nonredundant structure database and two sets of termini from the CASP8 targets. The performance of the terminus modeling method is significantly improved over our previous method that does not employ terminus refinement. It is also comparable or superior to the best server methods tested in CASP8. The success of the current approach suggests that similar strategy may be applied to other types of refinement problems such as loop modeling or secondary structure rearrangement. Copyright © 2011 Wiley-Liss, Inc.

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.

Radiochemical ageing of EPDM elastomers.. 2. Identification and quantification of chemical changes in EPDM and EPR films γ-irradiated under oxygen atmosphere

NASA Astrophysics Data System (ADS)

Rivaton, A.; Cambon, S.; Gardette, J.-L.

2005-01-01

This paper is devoted to the identification and quantification of the main chemical changes resulting from the radiochemical ageing under oxygen atmosphere of ethylene-propylene-diene monomer (EPDM) and ethylene-propylene rubber (EPR) films containing the same molar ratio of ethylene/propylene. IR and UV-Vis analysis showed that radiooxidation produces a complex mixture of different products and provokes the consumption of the diene double bond. The radiochemical yields of formation of ketones, carboxylic acids, hydroperoxides and alcohols were determined by combining IR analysis with derivatisation reactions and chemical titration. The contributions of secondary and tertiary structures of these two types of -OH groups were separated. Esters and γ-lactones were formed in low concentration. The oxidation products distribution in irradiated films was determined by micro-FTIR spectroscopy. Crosslinking was evaluated by gel fraction methods. In complement, the gas phase composition was analysed by mass spectrometry.

Isopach map of the interval from surface elevation to the top of the Pennsylvanian and Permian Minnelusa Formation and equivalents, Powder River basin, Wyoming and Montana

USGS Publications Warehouse

Crysdale, B.L.

1990-01-01

This map is one in a series of U.S. Geological Survey Miscellaneous Field Studies (MF) maps showing computer-generated structure contours, isopachs, and cross sections of selected formations in the Powder River basin, Wyoming and Montana. The map and cross sections were constructed from information stored in a U.S. Geological Survey Evolution of Sedimentary Basins data base. This data base contains picks of geologic formation and (or) unit tops and bases determined from electric resistivity and gamma-ray logs of 8,592 wells penetrating Tertiary and older rocks in the Powder River basin. Well completion cards (scout tickets) were reviewed and compared with copies of all logs, and formation or unit contacts determined by N. M. Denson, D.L. Macke, R. R. Schumann and others. This isopach map is based on information from 1,480 of these wells that penetrate the Minnelusa Formation and equivalents.

Map showing contours on the top of the Pennsylvanian and Permian Minnelusa Formation and equivalents, Powder River basin, Wyoming and Montana

USGS Publications Warehouse

Crysdale, B.L.

1990-01-01

This map is one in a series of U.S. Geological Survey Miscellaneous Field Studies (MF) maps showing computer-generated structure contours, isopachs, and cross sections of selected formations in the Powder River basin, Wyoming and Montana. The map and cross sections were constructed from information stored in a U.S. Geological Survey Evolution of Sedimentary Basins data base. This data base contains picks of geologic formation and (or) unit tops and bases determined from electric resistivity and gamma-ray logs of 8,592 wells penetrating Tertiary and older rocks in the Powder River basin. Well completion cards (scout tickets) were reviewed and compared with copies of all logs, and formation or unit contacts determined by N. M. Denson, D.L. Macke, R. R. Schumann and others. This isopach map is based on information from 1,480 of these wells that penetrate the Minnelusa Formation and equivalents.

MEDICAL AUDIT OF PATIENT CARE: A STUDY OF DOCTORS IN A TERTIARY HEALTH FACILITY IN SOUTH WEST NIGERIA.

PubMed

Ilesanmi, O S; Alele, F O

2015-01-01

The role of Medical Audit in patient care needs to beexplored. This study aimed to determine doctors' knowledge and practice of Medical Audit in a tertiary health facility in South West Nigeria. Across-sectional study of 115 consenting doctors at Federal Medical Centre Owo was conducted. A semi-structured, self-administered questionnaire was used. Data was analyzed using SPSS version 21. Descriptive statistics were presented using frequency tables and bar chart, age and year of practice were summarized as mean and standard deviation. Chi square-test was used to compare sociodemographic variables with doctor's knowledge of MedicalAudit. Level of statistical significant was 5%. The mean age of the respondents was 32.5 ± 5.8 years. Males were 78%, and 61.7% were married. The mean duration of practice was 3.3 ± 2.2 years. Adequate knowledge of Medical Audit was found in 79% of the respondents while only 53% had practiced it. Formal training on Medical Audit has not been received by 91.3% of the respondents, 80.9% requested for training on Medical Audit. In all, 88.0% who had ≥ 3-years of practice had adequate knowledge compared with only 72.3% of those who had less than three years of practice (p = 0.040). Practice of MedicalAudit is low though adequate knowledge exist.Training of doctors on Medical Audit is required.

Mortality pattern in otorhinolaryngology ward: A 5 years retrospective study at an urban tertiary health care center in India.

PubMed

Kumar, Vivek; Kumar, Satish; Chandra Sharma, Naresh; Kumar, Badal

2017-10-01

To recognize deaths in the otorhinolaryngology indoor wards, determine the reason behind the mortalities and recommend modifications for betterment of patient care and surgical outcomes. Data was collected from the mortality register, operation theatre registers, ward registers and case notes of patients declared dead at an urban tertiary health care center in India for a period of 5 years; from January 2012 to December 2016. The data included date of admission, age, sex, educational status, residence, and clinical diagnosis, course of hospital stay and medical cause of death. Data acquired was reviewed and statistically interpreted and presented in graphical and descriptive formats. 6157 admissions were made in otorhinolaryngology (ENT) ward in the 5 year period which included 3969 males and 2188 female patients. 58 deaths were recorded during this period which gives overall death per admission crude mortality rate of 9.42% at an average of about 12 (11.60) deaths per year. The major causes of death were malignancy and septicemia. The significance of health education, aggressive healthcare campaigns, enhancement of healthcare services and wide accessibility of healthcare services to remote areas has been emphasized. Role of structured study and protocols in the management of serious cases is highlighted along with the need for prompt referral and better interdepartmental cooperation. Copyright © 2017 Chang Gung University. Published by Elsevier B.V. All rights reserved.

Off-label and unlicensed drug use in hospitalized newborns in a Saudi tertiary care hospital: a cohort study.

PubMed

Mazhar, Faizan; Akram, Shahzad; Haider, Nafis; Hadi, Muhammad Abdul; Sultana, Jabeen

2018-06-01

Objective To determine the extent of off-label and unlicensed prescribing in hospitalized newborns and to identify patient-related risk factors associated with off-label prescribing. Methods A prospective cohort study was conducted between January and March 2016 at a neonatology department of a tertiary-care hospital in the Eastern province. All consecutive admissions to all neonatal care levels meeting the inclusion and exclusion criteria were eligible for enrollment. All prescriptions were classified as off-label or unlicensed according to drug product monograph. Clinical and prescription data were extracted using a pilot-tested structured data collection sheet. Results During the study period 583 prescriptions were made for 138 newborns, of which 29.7% (173/583) and 12.9% (75/583) were classified as off-label and unlicensed drugs respectively for use in neonates. Thirty-four percent (47/138) of patients received at least one off-label/unlicensed medicine. Mechanical ventilation, admission to the neonatal intensive care unit and length of hospital stay were identified as independent risk factors associated with prescribing of at least one off-label medication. Conclusion Use of off-label and unlicensed drugs in hospitalized newborns seems to be a common practice in this Saudi hospital. Future research should evaluate safety and efficacy of off-label and/or unlicensed use of drugs in neonates.

Metal Ion Dependence, Thermodynamics, and Kinetics for Intramolecular Docking of a GAAA Tetraloop and Receptor Connected by a Flexible Linker†

PubMed Central

Downey, Christopher D.; Fiore, Julie L.; Stoddard, Colby D.; Hodak, Jose H.; Nesbitt, David J.; Pardi, Arthur

2008-01-01

The GAAA tetraloop-receptor is a commonly occurring tertiary interaction motif in RNA. This motif usually occurs in combination with other tertiary interactions in complex RNA structures. Thus, it is difficult to measure directly the contribution that a single GAAA tetraloop-receptor interaction makes to the folding properties of an RNA. To investigate the kinetics and thermodynamics for the isolated interaction, a GAAA tetraloop domain and receptor domain were connected by a single-stranded A7 linker. Fluorescence resonance energy transfer (FRET) experiments were used to probe intramolecular docking of the GAAA tetraloop and receptor. Docking was induced using a variety of metal ions, where the charge of the ion was the most important factor in determining the concentration of the ion required to promote docking ([Co(NH3)63+] ≪ [Ca2+], [Mg2+], [Mn2+] ≪ [Na+], [K+]). Analysis of metal ion cooperativity yielded Hill coefficients of ≈ 2 for Na+- or K+-dependent docking versus ≈ 1 for the divalent ions and Co(NH3)63+. Ensemble stopped-flow FRET kinetic measurements yielded an apparent activation energy of 12.7 kcal/mol for GAAA tetraloop-receptor docking. RNA constructs with U7 and A14 single-stranded linkers were investigated by single-molecule and ensemble FRET techniques to determine how linker length and composition affect docking. These studies showed that the single-stranded region functions primarily as a flexible tether. Inhibition of docking by oligonucleotides complementary to the linker was also investigated. The influence of flexible versus rigid linkers on GAAA tetraloop-receptor docking is discussed. PMID:16533049

Distribution and predictors of emergency department charges: the case of a tertiary hospital in Lebanon.

PubMed

Saleh, Shadi; Mourad, Yara; Dimassi, Hani; Hitti, Eveline

2016-03-18

As health care costs continue to increase worldwide, health care systems, and more specifically hospitals are facing continuous pressure to operate more efficiently. One service within the hospital sector whose cost structure has been modestly investigated is the Emergency Department (ED). The study aims to report on the distribution of ED resource use, as expressed in charges, and to determine predictors of/contributors to total ED charges at a major tertiary hospital in Lebanon. The study used data extracted from the ED discharge database for visits between July 31, 2012 and July 31, 2014. Patient visit bills were reported under six major categories: solutions, pharmacy, laboratory, physicians, facility, and radiology. Characteristics of ED visits were summarized according to patient gender, age, acuity score, and disposition. Univariate and multivariate analyses were conducted with total charges as the dependent variable. Findings revealed that the professional fee (40.9 %) followed by facility fee (26.1 %) accounted for the majority of the ED charges. While greater than 80 % of visit charges went to physician and facility fee for low acuity cases, these contributed to only 52 and 54 % of the high acuity presentations where ancillary services and solutions' contribution to the total charges increased. The total charges for males were $14 higher than females; age was a predictor of higher charges with total charges of patients greater than 60 years of age being around $113 higher than ages 0-18 after controlling for all other variables. Understanding the components and determinants of ED charges is essential to developing cost-containment interventions. Institutional modeling of charging patterns can be used to offer price estimates to ED patients who request this information and ultimately help create market competition to drive down costs.

Structural variation in transition-metal bispidine compounds.

PubMed

Comba, Peter; Kerscher, Marion; Merz, Michael; Müller, Vera; Pritzkow, Hans; Remenyi, Rainer; Schiek, Wolfgang; Xiong, Yun

2002-12-16

The experimentally determined molecular structures of 40 transition metal complexes with the tetradentate bispyridine-substituted bispidone ligand, 2,4-bis(2-pyridine)-3,7-diazabicyclo[3.3.1]nonane-9-one [M(bisp)XYZ]n+; M = CrIII, MnII, FeII, CoII, CuII, CuI, ZnII; X, Y, Z = mono- or bidentate co-ligands; penta-, hexa- or heptacoordinate complexes) are characterized in detail, supported by force-field and DFT calculations. While the bispidine ligand is very rigid (N3...N7 distance = 2.933 +/- 0.025 A), it tolerates a large range of metal-donor bond lengths (2.07 A < sigma(M-N)/4 < 2.35 A). Of particular interest is the ratio of the bond lengths between the metal center and the two tertiary amine donors (0.84 A < M-N3/M-N7 < 1.05 A) and the fact that, in terms of this ratio there seem to be two clusters with M-N3 < M-N7 and M-N3 > or = M-N7. Calculations indicate that the two structural types are close to degenerate, and the structural form therefore depends on the metal ion, the number and type of co-ligands, as well as structural variations of the bispidine ligand backbone. Tuning of the structures is of importance since the structurally differing complexes have very different stabilities and reactivities.

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.

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.

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.

Transport and fate of microplastic particles in wastewater treatment plants.

PubMed

Carr, Steve A; Liu, Jin; Tesoro, Arnold G

2016-03-15

Municipal wastewater treatment plants (WWTPs) are frequently suspected as significant point sources or conduits of microplastics to the environment. To directly investigate these suspicions, effluent discharges from seven tertiary plants and one secondary plant in Southern California were studied. The study also looked at influent loads, particle size/type, conveyance, and removal at these wastewater treatment facilities. Over 0.189 million liters of effluent at each of the seven tertiary plants were filtered using an assembled stack of sieves with mesh sizes between 400 and 45 μm. Additionally, the surface of 28.4 million liters of final effluent at three tertiary plants was skimmed using a 125 μm filtering assembly. The results suggest that tertiary effluent is not a significant source of microplastics and that these plastic pollutants are effectively removed during the skimming and settling treatment processes. However, at a downstream secondary plant, an average of one micro-particle in every 1.14 thousand liters of final effluent was counted. The majority of microplastics identified in this study had a profile (color, shape, and size) similar to the blue polyethylene particles present in toothpaste formulations. Existing treatment processes were determined to be very effective for removal of microplastic contaminants entering typical municipal WWTPs. Published by Elsevier Ltd.

Determinants of Teaching as a Career in the UK

ERIC Educational Resources Information Center

See, Beng Huat

2004-01-01

This paper models the likelihood of individuals becoming teachers, to identify the key social and economic determinants of selecting teaching as a career in the UK. E-mail and focus group interviews were used to develop a questionnaire, for surveying a sample of 1845 students and professional trainees from four tertiary institutions in South-west…

Lecturer Quality, Quantity and Gender in Colleges of Education in Nigeria

ERIC Educational Resources Information Center

Arubayi, D. O.

2009-01-01

The quality and quantity of lecturers in Tertiary institutions to a great extent determines the quality of graduates. To ensure quality and quantity the Colleges of Education in Nigeria have established internal and external mechanisms. Quantity is determined by the number of students to a given lecturer. Despite the mechanism put forward to…

Structural characterization of framework-gas interactions in the metal-organic framework Co2(dobdc) by in situ single-crystal X-ray diffraction.

PubMed

Gonzalez, Miguel I; Mason, Jarad A; Bloch, Eric D; Teat, Simon J; Gagnon, Kevin J; Morrison, Gregory Y; Queen, Wendy L; Long, Jeffrey R

2017-06-01

The crystallographic characterization of framework-guest interactions in metal-organic frameworks allows the location of guest binding sites and provides meaningful information on the nature of these interactions, enabling the correlation of structure with adsorption behavior. Here, techniques developed for in situ single-crystal X-ray diffraction experiments on porous crystals have enabled the direct observation of CO, CH 4 , N 2 , O 2 , Ar, and P 4 adsorption in Co 2 (dobdc) (dobdc 4- = 2,5-dioxido-1,4-benzenedicarboxylate), a metal-organic framework bearing coordinatively unsaturated cobalt(ii) sites. All these molecules exhibit such weak interactions with the high-spin cobalt(ii) sites in the framework that no analogous molecular structures exist, demonstrating the utility of metal-organic frameworks as crystalline matrices for the isolation and structural determination of unstable species. Notably, the Co-CH 4 and Co-Ar interactions observed in Co 2 (dobdc) represent, to the best of our knowledge, the first single-crystal structure determination of a metal-CH 4 interaction and the first crystallographically characterized metal-Ar interaction. Analysis of low-pressure gas adsorption isotherms confirms that these gases exhibit mainly physisorptive interactions with the cobalt(ii) sites in Co 2 (dobdc), with differential enthalpies of adsorption as weak as -17(1) kJ mol -1 (for Ar). Moreover, the structures of Co 2 (dobdc)·3.8N 2 , Co 2 (dobdc)·5.9O 2 , and Co 2 (dobdc)·2.0Ar reveal the location of secondary (N 2 , O 2 , and Ar) and tertiary (O 2 ) binding sites in Co 2 (dobdc), while high-pressure CO 2 , CO, CH 4 , N 2 , and Ar adsorption isotherms show that these binding sites become more relevant at elevated pressures.

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.

Biospheric effects of a large extraterrestrial impact: Case study of the Cretaceous/Tertiary boundary crater

NASA Technical Reports Server (NTRS)

Pope, Kevin O.

1994-01-01

The Chicxulub Crater in Yucatan, Mexico, is the primary candidate for the impact that caused mass extinctions at the Cretaceous/Tertiary boundary. The target rocks at Chicxulub contain 750 to 1500 m of anhydrite (CaSO4), which was vaporized upon impact, creating a large sulfuric acid aerosol cloud. In this study we apply a hydrocode model of asteroid impact to calculate the amount of sulfuric acid produced. We then apply a radiative transfer model to determine the atmospheric effects. Results include 6 to 9 month period of darkness followed by 12 to 26 years of cooling.

Preliminary isostatic gravity map of the Sonoma volcanic field and vicinity, Sonoma and Napa Counties, California

USGS Publications Warehouse

Langenheim, V.E.; Roberts, C.W.; McCabe, C.A.; McPhee, D.K.; Tilden, J.E.; Jachens, R.C.

2006-01-01

This isostatic residual gravity map is part of a three-dimensional mapping effort focused on the subsurface distribution of rocks of the Sonoma volcanic field in Napa and Sonoma counties, northern California. This map will serve as a basis for modeling the shapes of basins beneath the Santa Rosa Plain and Napa and Sonoma Valleys, and 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 explained below) 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 boundaries. High-density basement rocks exposed within the northern San Francisco Bay area include those of the Mesozoic Franciscan Complex and Great Valley Sequence present in the mountainous areas of the quadrangle. Alluvial sediment 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 in densities, but, on average, are less dense than the Mesozoic basement rocks. Isostatic residual gravity values within the map area range from about -41 mGal over San Pablo Bay to about 11 mGal near Greeg Mountain 10 km east of St. Helena. Steep linear gravity gradients are coincident with the traces of several Quaternary strike-slip faults, most notably along the West Napa fault bounding the west side of Napa Valley, the projection of the Hayward fault in San Pablo Bay, the Maacama Fault, and the Rodgers Creek fault in the vicinity of Santa Rosa. These gradients result from juxtaposing dense basement rocks against thick Tertiary volcanic and sedimentary rocks.

Consumption processes and food web structure in the Columbia River Estuary

NASA Astrophysics Data System (ADS)

Simenstad, Charles A.; Small, Lawrence F.; David McIntire, C.

Consumption processes at several trophic levels tend to coverage in the central (estuarine-mixing) region of the Columbia River estuary, where living and dentrital food resources are entrained within the energy null of the turbidity maximum zone. Primary consumers in this region are generalist and omnivorous feeders, capable of exploiting both autotrophic and heterotrophic food web pathways. In the presence of higher standing stocks of their prey resources, feeding by secondary and tertiary consumers is also concentrated, or more effective, in the estuarine mixing region of the estuary. During the 1980-1981 studies of the estuary, total consumer (metazoan) production averaged 5.5g C m -2 within the estuary. Of the estimated 15 x 10 3mt Cyy -1 attributed to primary consumption in the water column, 83% was the result of suspension-feeding pelagic zooplankton. In comparison to grazing on phytoplankton, it was estimated that approximately 84% of primary consumption in the water column was based on suspended detritus and, presumably, associated microbiota. Endemic primary,consumers, principally epibenthic crustaceans such as the calanoid copepod Eurytemora affinis, the harpacticoid copepod Scottolana canadensis, and the crangonid shrimp Crangon franciscorum, accounted for a high proportion of the consumption of suspended particles. Wertland herbivores inhabiting the estuary's extensive marshes, on the other hand, were estimated to account for only 2 to 17% of total estuarine primary consumption. Trophic linkages to secondary and tertiary consumers were more evenly apportioned among pelagic fishes, motile macroinvertebrates, and benthic infauna. High, comparatively unknown fluxes of migratory or wide-ranging tertiary consumers, such as piscivorous birds, seals and sea lions, made estimation of their annual consumption rates in the estuary highly tenuous. The physical processes of mixing and stratification, sediments accretion and erosion, and salinity intrusion appear to be the fundamental determinants of consumption processes in the Columbia River estuary, and perhaps in other similarly energetic estuarine systems, by promoting concentrations of consumers in low-energy habitats such as the turbidity maximum and peripheral bays.

A Mixed-methods Study to Assess Interrater Reliability and Nurse Perception of the Braden Scale in a Tertiary Acute Care Setting.

PubMed

Ho, Chester H; Cheung, Amanda; Southern, Danielle; Ocampo, Wrechelle; Kaufman, Jaime; Hogan, David B; Baylis, Barry; Conly, John M; Stelfox, Henry T; Ghali, William A

2016-12-01

Research regarding the reliability of the Braden Scale and nurses' perspectives on the instrument for predicting pressure ulcer (PU) risk in acute care settings is limited. A mixed-methods study was conducted in a tertiary acute care facility to examine interrater reliability (IRR) of the Braden Scale and its subscales, and a qualitative survey using semi-structured interviews was conducted among nurses caring for patients in acute care units to gain nurse perspective regarding scale usability. Data were extracted from a previous retrospective, randomized, controlled trial involving adult patients with compromised mobility receiving care in a tertiary acute care hospital in Canada. One-way, intraclass correlation coefficients (ICCs) were calculated on item and total scores, and kappa statistics were used to determine reliability of categorizing patients on their risk. Interview results were categorized by common themes. Reliability was assessed on 64 patients, where nurses and research staff independently assessed enrolled participants at baseline and after 72 hours using the Braden Scale as it appeared on an electronic medical record. IRR for the total score was high (ICC = 0.807). The friction and shear item had the lowest reliability (ICC = 0.266). Reliability of categorizing patients' level of risk had moderate agreement (κ = 0.408). Three (3) major and 12 subthemes emerged from the 14 nurse interviews; nurses were aware of the scale's purpose but were uncertain of its effectiveness, some items were difficult to rate, and questions were raised as to whether using the scale enhanced patient care. Aspects identified by nurses to enhance usability included: 1) changes to the electronic version (incorporating the scale into daily assessment documents with readily available item descriptions), 2) additional training, and 3) easily available resource material to improve reliability and usability of scale. These findings need to be considered when using the Braden Scale in clinical practice. Further study of the value of the total Braden Scale and its subscales is warranted.

An analysis of gravity data in Area 12, Nevada Test Site

USGS Publications Warehouse

Wahl, R.R.

1969-01-01

The gravity data available from Healey and Miller (1963a) were augmented by new observations along three profiles through two new drill holes in Area 12; UEI2t #1 and UEI2p #1. The data were interpreted to allow evaluation of the geologic structure prior to the planning and excavation of two proposed tunnel complexes, Ul2t and Ul2p. Density values for each of six rock units were determined to allow a two-dimensional analysis of the gravity data along the above-mentioned profiles. The surficial rocks of Quaternary and Tertiary age and the Tertiary volcanic rocks have a weighted average density of 1.86 gm/cc. The density of the caprock at Rainier and Aqueduct Mesas ranges from 2.17 gm/cc at UEI2p #1 to 2.27 gm/cc at UEI2t #1. The Gold Meadows stock and the associated Precambrian quartzite have an arithmetic average density of 2.60 gm/cc for all samples measured. The middle Paleozoic dolomite in Area 12 has an arithmetic average density of 2.75 gm/cc. The clastic rocks of Paleozoic age have an arithmetic average density of 2.60 gm/cc. Interpretation of the residual gravity data indicates a maximum thickness of about 2,800 feet for all Tertiary volcanic rocks. A normal fault striking N. 30 ? E. disrupts the pre-Cenozoic surface at UEI2p #1 and 0.4 mile east of UEI2t #1. The throw within rock of Paleozoic age is about 400-500 feet. Another normal fault that strikes about N. 20 ? E. is located about 1.5 miles east of UEI2p #1. The throw of this fault is at least 1,100 feet in rocks of pre-Cenozoic age. Elevation contours representing the pre-Cenozoic surface in Area 12 show a maximum relief of about 2,000 feet.

Knowledge and behavior towards voluntary blood donation among students of a tertiary institution in Nigeria.

PubMed

Salaudeen, A G; Odeh, E

2011-01-01

Blood donation is the only way of acquiring blood to meet emergency requirements in cases of road traffic accidents, complications of pregnancy and childbirth, various anemic disorders and surgical emergencies among others. Globally, 80 million units of blood are donated each year, but only two million units are donated in sub-Saharan Africa where the need is enormous. The objective of this study was to determine the behavior of the students of a tertiary institution in Nigeria towards voluntary blood donation. This is a descriptive cross-sectional study, which involved students of a tertiary institution in Nigeria. A multistage sampling technique was employed in selecting the participants for this study. A semi-structured self-administered questionnaire was used to collect information on socio-demographic characteristics, knowledge, attitude and factors affecting voluntary blood donation. The data obtained were analyzed using EPI-INFO 2005 software Version 3.3.2. Less than two-thirds (61%) of total respondents had good knowledge of blood donation. More than three quarters (85%) of the respondents had never donated blood. Of the 15% that had donated, only 3% donated voluntarily. Among those that had ever donated, males (57%) were more than females. Many of the donors donated for relatives (57%). The majority of the respondents were compelled to donate because of emergency situations (75%). The reasons why many did not donate were lack of opportunity (45%) due to tight lecture schedule and inadequate knowledge (24%). Gift items such as hematinics, T-shirts and wrist bands (29%) would motivate respondents to donate. The Students' Union body and other Organizations in the University should include a blood donation drive in their monthly/annual activities. The University authorities, the University health service centre and the Hematology Department of the Teaching hospital should collaborate in promoting voluntary blood donation among the students.

Environmental risk assessment of effluents as a whole emerging contaminant: Efficiency of alternative tertiary treatments for wastewater depuration.

PubMed

Díaz-Garduño, B; Pintado-Herrera, M G; Biel-Maeso, M; Rueda-Márquez, J J; Lara-Martín, P A; Perales, J A; Manzano, M A; Garrido-Pérez, C; Martín-Díaz, M L

2017-08-01

Emerging contaminants (ECs) and regulated compounds (RCs) from three different WWTP effluents were measured in the current study. The efficiency of two tertiary treatments, Photobiotreatment (PhtBio) and Multi-Barrier Treatment (MBT), for removing contaminants was determined. Results indicated different percentages of removal depending on the treatment and the origin of the effluent. Risk Quotients (RQs) were determined for different species of algae, Daphnia, and fish. RQ results revealed diverse risk values depending on the bioindicator species. Tonalide, galaxolide (fragrances), and ofloxacin (antibiotic) were the most persistent and harmful substances in tested effluents. "Negligible risk" category was reached since a wide diversity of ECs were removed by MBT with high removal percentages. Contrarily, PhtBio was effective only in the depuration of certain chemical compounds, and its efficiency depended on the composition of the raw effluent. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prevalence of epilepsy and seizure disorders as causes of apparent life- threatening event (ALTE) in children admitted to a tertiary hospital.

PubMed

Anjos, Alessandra Marques dos; Nunes, Magda Lahorgue

2009-09-01

To determine the prevalence and describe clinical characteristics of seizure disorders and epilepsy as causes of apparent life- threatening event (ALTE) in children admitted at the emergency and followed in a tertiary hospital. Cross-sectional study with prospective data collection using specific guidelines to determine the etiology of ALTE. During the study, 30 (4.2%) children admitted to the hospital had a diagnosis of ALTE. There was a predominance of males (73%) and term infants (70%). Neonatal neurological disorders and neuropsychomotor development delay were found respectively in 13.4% and 10% of the cases. Etiological investigation revealed that 50% of the cases were idiopathic, and 13.4% were caused by epilepsy or seizure disorders. Although all patients had recurrent ALTE events, epilepsy had not been previously suspected. Epilepsy should be included in the differential diagnosis of ALTE, particularly when events are recurrent.

Utility of video-EEG monitoring in a tertiary care epilepsy center.

PubMed

Kumar-Pelayo, M; Oller-Cramsie, M; Mihu, N; Harden, C

2013-09-01

Our video-EEG monitoring (VEEG) unit is part of a typical metropolitan tertiary care center that services a diverse patient population. We aimed to determine if the specific clinical reason for inpatient VEEG was actually resolved. Our method was to retrospectively determine the stated goal of inpatient VEEG and to analyze the outcome of one hundred consecutive adult patients admitted for VEEG. The reason for admission fit into one of four categories: 1) to characterize paroxysmal events as either epileptic or nonepileptic, 2) to localize epileptic foci, 3) to characterize the epilepsy syndrome, and 4) to attempt safe antiepileptic drug adjustment. We found that VEEG was successful in accomplishing the goal of admission in 77% of cases. The remaining 23% failed primarily due to lack of typical events during monitoring. Furthermore, of the overall study cohort, VEEG outcomes altered medical management in 53% and surgery was pursued in 5%. © 2013.

Interhospital paediatric intensive care transport: a novel transport unit based on a standard ambulance trolley.

PubMed

Vos, Gijs D; Buurman, Wim A; van Waardenburg, Dick A; Visser, Timo P L; Ramsay, Graham; Donckerwolcke, Raymond A M G

2003-09-01

A recent development in providing intensive care for children is that it is more and more centralized in tertiary centres. The centralization of intensive care facilities for children in tertiary centres demands a safe and well-organized transport system. The transfer of critically ill children from a referring general hospital to a tertiary paediatric intensive care centre should be performed by a specially trained and fully equipped transport team. During the transfer of these children continuous intensive care facilities should be provided. The minimal requirements of equipment and materials for transport that allow such care have been determined. The equipment consists of a monitor allowing continuous measurement of vital signs, a defibrillator, tools for airway and ventilatory management, an oxygen source, suction unit, fluid and electrolyte management, medication, resuscitation chart and a communication system. A mobile paediatric intensive care unit was constructed in order to store this equipment, including easily accessible ventilator and materials optimized for close patient observation and ventilator control.

[Experience of the surgical management of the esophageal achalasia in a tertiary care hospital].

PubMed

Barajas-Fregoso, Elpidio Manuel; Romero-Hernández, Teodoro; Sánchez-Fernández, Patricio Rogelio; Fuentes-Orozco, Clotilde; González-Ojeda, Alejandro; Macías-Amezcua, Michel Dassaejv

2015-01-01

Achalasia is a primary esophageal motor disorder. The most common symptoms are: dysphagia, chest pain, reflux and weight loss. The esophageal manometry is the standard for diagnosis. The aim of this paper is to determine the effectiveness of the surgical management in patients with achalasia in a tertiary care hospital. A case series consisting of achalasia patients, treated surgically between January and December of 2011. Clinical charts were reviewed to obtain data and registries of the type of surgical procedure, morbidity and mortality. Fourteen patients were identified, with an average age of 49.1 years. The most common symptoms were: dysphagia, vomiting, weight loss and pyrosis. Eight open approaches were performed and six by laparoscopy, with an average length of cardiomyotomy of 9.4 cm. Eleven patients received an antireflux procedure. The effectiveness of procedures performed was 85.7 %. Surgical management offered at this tertiary care hospital does not differ from that reported in other case series, giving effectiveness and safety for patients with achalasia.

Nitrosamine formation in amine scrubbing at desorber temperatures.

PubMed

Fine, Nathan A; Goldman, Mark J; Rochelle, Gary T

2014-01-01

Amine scrubbing is a thermodynamically efficient and industrially proven method for carbon capture, but amine solvents can nitrosate in the desorber, forming potentially carcinogenic nitrosamines. The kinetics of reactions involving nitrite and monoethanolamine (MEA), diethanolamine (DEA), methylethanolamine (MMEA), and methyldiethanolamine (MDEA) were determined under desorber conditions. The nitrosations of MEA, DEA, and MMEA are first order in nitrite, carbamate species, and hydronium ion. Nitrosation of MDEA, a tertiary amine, is not catalyzed by the addition of CO2 since it cannot form a stable carbamate. Concentrated and CO2 loaded MEA was blended with low concentrations of N-(2-hydroxyethyl) glycine (HeGly), hydroxyethyl-ethylenediamine (HEEDA), and DEA, secondary amines common in MEA degradation. Nitrosamine yield was proportional to the concentration of secondary amine and was a function of CO2 loading and temperature. Blends of tertiary amines with piperazine (PZ) showed n-nitrosopiperazine (MNPZ) yields close to unity, validating the slow nitrosation rates hypothesized for tertiary amines. These results provide a useful tool for estimating nitrosamine accumulation over a range of amine solvents.

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

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

Unlicensed and off-label use of drugs in pediatric surgical units at tertiary care hospitals of Pakistan.

PubMed

Aamir, Muhammad; Khan, Jamshaid Ali; Shakeel, Faisal; Asim, Syed Muhammad

2017-08-01

Background Unlicensed and off-label prescribing practice is global dilemma around the world. This pioneering study was designed to determine unlicensed and off-label use of drug in surgical wards of tertiary care hospitals of Pakistan. Objective To assess unlicensed and off-label use of drugs in pediatric surgical unit at three tertiary care hospitals in Peshawar, Pakistan. Setting Two government and one private tertiary care hospitals in Pakistan. Method Drug profiles of 895 patients from three different clinical settings were evaluated for unlicensed and off-label use of drugs using Micromedex DRUGDEX. Main outcome measure Characteristics of the unlicensed and off-label drug prescriptions. Result Total of 3168 prescribed drugs were analyzed in this study. Indication (38.7%) and dose (34.8%) were the most frequent off-label categories. In comparison with the corresponding reference categories, infants and children, male patients and having less than five prescribed drugs were significant predictors of unlicensed prescriptions. In comparison with the corresponding reference categories, significant predictors of off-label drug prescribing were children younger than two year, children between 2-12 years, patient staying at hospital less than 5 days and patients having less than five prescribed drugs. Conclusion The prevalence of unlicensed and off-label drug prescriptions are high at pediatric surgical ward of tertiary care hospitals. More awareness of the efficacy and safety of drugs are required in pediatrics. In addition, new formulations with advanced dosing for children are also required to minimize the risk of adverse outcomes.

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

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.

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.

DWARF – a data warehouse system for analyzing protein families

PubMed Central

Fischer, Markus; Thai, Quan K; Grieb, Melanie; Pleiss, Jürgen

2006-01-01

Background The emerging field of integrative bioinformatics provides the tools to organize and systematically analyze vast amounts of highly diverse biological data and thus allows to gain a novel understanding of complex biological systems. The data warehouse DWARF applies integrative bioinformatics approaches to the analysis of large protein families. Description The data warehouse system DWARF integrates data on sequence, structure, and functional annotation for protein fold families. The underlying relational data model consists of three major sections representing entities related to the protein (biochemical function, source organism, classification to homologous families and superfamilies), the protein sequence (position-specific annotation, mutant information), and the protein structure (secondary structure information, superimposed tertiary structure). Tools for extracting, transforming and loading data from public available resources (ExPDB, GenBank, DSSP) are provided to populate the database. The data can be accessed by an interface for searching and browsing, and by analysis tools that operate on annotation, sequence, or structure. We applied DWARF to the family of α/β-hydrolases to host the Lipase Engineering database. Release 2.3 contains 6138 sequences and 167 experimentally determined protein structures, which are assigned to 37 superfamilies 103 homologous families. Conclusion DWARF has been designed for constructing databases of large structurally related protein families and for evaluating their sequence-structure-function relationships by a systematic analysis of sequence, structure and functional annotation. It has been applied to predict biochemical properties from sequence, and serves as a valuable tool for protein engineering. PMID:17094801

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.

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.

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.

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.

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.

What Interventions Are Being Used to Prevent Preterm Birth and When?

PubMed

Feng, Yu Yang; Jarde, Alexander; Seo, Ye Rin; Powell, Anne; Nwebube, Nwachukwu; McDonald, Sarah D

2018-05-01

This study sought to determine the proportions of women at risk of preterm birth who received progesterone, elective and rescue cerclage, or pessary to prevent preterm birth, by using medical records. The authors also sought to determine whether these proportions differed among primary-, secondary-, and tertiary-level centres. The authors conducted a retrospective cohort study and extracted data from consecutive medical charts of women with an estimated date of confinement over 3 months in primary-, secondary-, and tertiary-level centres in Southern Ontario. The study identified women with a previous spontaneous preterm birth or a short cervix and determined whether they were offered and whether they received a preventive intervention for preterm birth. Descriptive statistics and Fisher exact tests were calculated. The authors reviewed 1024 consecutive charts at primary, secondary, and tertiary centres and identified 31 women with a previous spontaneous preterm birth or a short cervix. Of these women, less than one half (42%) received progesterone or cerclage for prevention of preterm birth, and none received pessary. One in four women (26%) were not referred to an obstetrician or maternal-fetal medicine specialist in time for an intervention, and among those referred before 24 weeks of gestation, an intervention was offered to 57% of the women. Less than half of women at risk of spontaneous preterm birth received progesterone, cerclage, or pessary, attesting to the importance of improving knowledge translation methods to encourage timely referral and use of progesterone for the prevention of preterm birth. Copyright © 2018 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved.

Conformational Toggling of Yeast Iso-1-Cytochrome c in the Oxidized and Reduced States

PubMed Central

Yang, Zhongzheng; Zhu, Jing; Ying, Tianlei; Jiang, Xianwang; Zhang, Xu; Wu, Houming; Liu, Maili; Tan, Xiangshi; Cao, Chunyang; Huang, Zhong-Xian

2011-01-01

To convert cyt c into a peroxidase-like metalloenzyme, the P71H mutant was designed to introduce a distal histidine. Unexpectedly, its peroxidase activity was found even lower than that of the native, and that the axial ligation of heme iron was changed to His71/His18 in the oxidized state, while to Met80/His18 in the reduced state, characterized by UV-visible, circular dichroism, and resonance Raman spectroscopy. To further probe the functional importance of Pro71 in oxidation state dependent conformational changes occurred in cyt c, the solution structures of P71H mutant in both oxidation states were determined. The structures indicate that the half molecule of cyt c (aa 50–102) presents a kind of “zigzag riveting ruler” structure, residues at certain positions of this region such as Pro71, Lys73 can move a big distance by altering the tertiary structure while maintaining the secondary structures. This finding provides a molecular insight into conformational toggling in different oxidation states of cyt c that is principle significance to its biological functions in electron transfer and apoptosis. Structural analysis also reveals that Pro71 functions as a key hydrophobic patch in the folding of the polypeptide of the region (aa 50–102), to prevent heme pocket from the solvent. PMID:22087268

Effect of ultrasound treatment on the wet heating Maillard reaction between mung bean [Vigna radiate (L.)] protein isolates and glucose and on structural and physico-chemical properties of conjugates.

PubMed

Wang, Zhongjiang; Han, Feifei; Sui, Xiaonan; Qi, Baokun; Yang, Yong; Zhang, Hui; Wang, Rui; Li, Yang; Jiang, Lianzhou

2016-03-30

The objective of this study was to determine the effect of ultrasound treatment on the wet heating Maillard reaction between mung bean protein isolates (MBPIs) and glucose, and on structural and physico-chemical properties of the conjugates. The degree of glycosylation of MBPI-glucose conjugates treated by ultrasound treatment and wet heating (MBPI-GUH) was higher than that of MBPI-glucose conjugates only treated by wet heating (MBPI-GH). Solubility, emulsification activity, emulsification stability and surface hydrophobicity of MBPI-GUH were higher than that of MBPI-GH. Grafted MBPIs had a lower content of α-helix and unordered coil, but a higher content of β-sheet and β-turn structure than MBPIs. No significant structural changes were observed in β-turn and random coil structure of MBPI-GUH, while α-helix content increased with ultrasonic time, and decreased at 300 W ultrasonic power with the increase of β-sheet. MBPI-GUH had a less compact tertiary structure compared to MBPI-GH and MBPI. Grafting MBPIs with glucose formed conjugates of higher molecular weight, while no significant changes were observed in electrophoresis profiles of MBPI-GUH. Ultrasound-assisted wet heating Maillard reaction between MBPIs and glucose could be a promising way to improve functional properties of MBPIs. © 2015 Society of Chemical Industry.

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

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.

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.

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.

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

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